Arxiu d'etiquetes: tòxic

Pharmacogenetics: a drug for each person

Sometimes, some people say that the medications prescribed by doctors are not good. Can this be true? Not all drugs work for the same population. Keep reading and discover the secrets of pharmacogenetics.

INTRODUCTION

The same that happens with nutrients, happens with drugs. Another objective of personalized medicine is to make us see that not all medicines are for everyone. However, it does not come again because around 1900, the Canadian physician William Osler recognized that there was an intrinsic and specific variability of everyone, so that each one reacts differently to a drug. This is how, years later, we would define pharmacogenetics.

It is important to point out that it is not the same as pharmacogenomics, which studies the molecular and genetic bases of diseases to develop new treatment routes.

First, we need to start at the beginning: what is a drug? Well, a drug is any physicochemical substance that interacts with the body and modifies it, to try to cure, prevent or diagnose a disease. It is important to know that drugs regulate functions that our cells do, but they are not capable of creating new functions.

Apart from knowing if a drug is good or not for a person, you also have to take into account the amount that should be administered. And we still do not know the origin of all diseases, that is, we do not know most of the real molecular and genetic causes of diseases.

The classification of diseases is based mainly on symptoms and signs and not on molecular causes. Sometimes, the same group of pathologies is grouped, but among them there is a very different molecular basis. This means that the therapeutic efficacy is limited and low. Faced with drugs, we can manifest a response, a partial response, that produces no effect or that the effect is toxic (Figure 1).

efectivitat i toxicitat
Figure 1. Drug toxicity. Different colours show possible responses (green: drug not toxic and beneficial; blue: drug not toxic and not beneficial; red: drug toxic but not beneficial; yellow: drug toxic but beneficial) (Source: Mireia Ramos, All You Need is Biology)

DRUGS IN OUR BODY

Drugs usually make the same journey through our body. When we take a drug, usually through the digestive tract, it is absorbed by our body and goes to the bloodstream. The blood distributes it to the target tissues where it must take effect. In this case we talk about active drug (Figure 2). But this is not always the case, but sometimes it needs to be activated. That’s when we talk about a prodrug, which needs to stop in the liver before it reaches the bloodstream.

Most of the time, the drug we ingest is active and does not need to visit the liver.

active and prodrug
Figure 2. Difference between prodrug and active drug (Source: Agent of Chemistry – Roger Tam)

Once the drug has already gone to the target tissue and has interacted with target cells, drug waste is produced. These wastes continue to circulate in the blood to the liver, which metabolizes them to be expelled through one of the two routes of expulsion: (i) bile and excretion together with the excrement or (ii) purification of the blood by the kidneys and the urine.

THE IMPORTANCE OF PHARMACOGENETICS

A clear example of how according to the polymorphisms of the population there will be different response variability we find in the transporter genes. P glycoprotein is a protein located in the cell membrane, which acts as a pump for the expulsion of xenobiotics to the outside of the cell, that is, all chemical compounds that are not part of the composition of living organisms.

Humans present a polymorphism that has been very studied. Depending on the polymorphism that everyone possesses, the transporter protein will have normal, intermediate or low activity.

In a normal situation, the transporter protein produces a high excretion of the drug. In this case, the person is a carrier of the CC allele (two cytokines). But if you only have one cytosine, combined with one thymine (both are pyrimidine bases), the expression of the gene is not as good, and the expulsion activity is lower, giving an intermediate situation. In contrast, if a person has two thymines (TT), the expression of the P glycoprotein in the cell membrane will be low. This will suppose a smaller activity of the responsible gene and, consequently, greater absorption in blood since the drug is not excreted. This polymorphism, the TT polymorphism, is dangerous for the patient, since it passes a lot of drug to the blood, being toxic for the patient. Therefore, if the patient is TT the dose will have to be lower.

This example shows us that knowing the genome of each individual and how their genetic code acts based on it, we can know if the administration of a drug to an individual will be appropriate or not. And based on this, we can prescribe another medication that is better suited to this person’s genetics.

 APPLICATIONS OF THE PHARMACOGENETICS

The applications of these disciplines of precision medicine are many. Among them are optimizing the dose, choosing the right drug, giving a prognosis of the patient, diagnosing them, applying gene therapy, monitoring the progress of a person, developing new drugs and predicting possible adverse responses.

The advances that have taken place in genomics, the design of drugs, therapies and diagnostics for different pathologies, have advanced markedly in recent years, and have given way to the birth of a medicine more adapted to the characteristics of each patient. We are, therefore, on the threshold of a new way of understanding diseases and medicine.

And this occurs at a time when you want to leave behind the world of patients who, in the face of illness or discomfort, are treated and diagnosed in the same way. By routine, they are prescribed the same medications and doses. For this reason, the need has arisen for a scientific alternative that, based on the genetic code, offers to treat the patient individually.

REFERENCES

  • Goldstein, DB et al. (2003) Pharmacogenetics goes genomic. Nature Review Genetics 4:937-947
  • Roden, DM et al. (2002) The genetic basis of variability in drug responses. Nature Reviews Drug Discovery 1:37-44
  • Wang, L (2010) Pharmacogenomics: a system approach. Syst Biol Med 2:3-22
  • Ramos, M. et al. (2017) El código genético, el secreto de la vida. RBA Libros
  • Main picture: Duke Center for Applied Genomics & Precision Medicine

MireiaRamos-angles2

 

La farmacogenètica: un fàrmac per a cada persona

Qui no ha sentit a algú queixar-se de que els medicaments receptats pels metges no li fan res? Pot ser això cert? No tots els fàrmacs serveixen per a la mateixa població. Segueix llegint i descobreix els secrets de la farmacogenètica.

INTRODUCCIÓ

El mateix que passa amb els nutrients, passa amb els fàrmacs. Un altre dels objectius de la medicina personalitzada és fer-nos veure que no tots els medicaments serveix per a totes les persones. No obstant, això no és nou perquè cap allà al 1900, el metge canadenc William Osler va reconèixer que existia una variabilitat intrínseca i pròpia de cada individu, de manera que cada persona reacciona de forma diferent davant d’un fàrmac. És així com anys més tard definiríem la farmacogenètica.

És important assenyalar que no és el mateix que la farmacogenómica, la qual estudia les bases moleculars i genètiques de les malalties per desenvolupar noves vies de tractament.

Abans de tot necessitem començar pel principi: què és un fàrmac? Doncs bé, un fàrmac és tota substància fisicoquímica que interactua amb l’organisme i el modifica, per tractar de curar, prevenir o diagnosticar una malaltia. És important saber que els fàrmacs regulen funcions que fan les nostres cèl·lules, però no són capaces de crear noves funcions.

A part de conèixer si un fàrmac és bo o no per a una persona, també s’ha de tenir en compte la quantitat d’aquest que s’ha d’administrat. I és que encara no coneixem l’origen de totes les malalties, és a dir, desconeixem la majoria de les causes moleculars i genètiques reals de les malalties.

La classificació de les malalties es basa principalment en símptomes i signes i no en les causes moleculars. A vegades, un mateix grup de patologies és agrupat, però entre ells existeix una base molecular molt diferent. Això comporta que l’eficàcia terapèutica sigui limitada i baixa. Davant els fàrmacs, podem manifestar una resposta, una resposta parcial, que no ens produeixi cap efecte o que l’efecte sigui tòxic (Figura 1).

efectivitat i toxicitat
Figura 1. Efectivitat i toxicitat d’un fàrmac a la població. Els diferents colors mostren les diferents respostes (verd: efectiu i segur; blau: segur, però no efectiu; vermell: tòxic i no efectiu; groc: tòxic, però efectiu) (Font: Mireia Ramos, All You Need is Biology)

ELS FÀRMACS AL NOSTRE COS

Els fàrmacs acostumen a fer el mateix recorregut pel nostre cos. Quan ens prenem un fàrmac, normalment per via digestiva, aquest és absorbit pel nostre cos i va a parar al torrent sanguini. La sang el distribueix als teixits diana on ha de fer efecte. En aquest cas parlem de fàrmac actiu (Figura 2). Però no sempre és així, sinó que a vegades necessita activar-se. És llavors quan parlem de profàrmac, el qual necessita fer escala al fetge abans d’aterrar al torrent sanguini.

La majoria de les vegades, el fàrmac que ingerim és actiu i no necessita passa a visitar al fetge.

active and prodrug
Figura 2. Diferència entre un profármac i un fármac actiu (Font: Agent of Chemistry – Roger Tam)

Una vegada que el fàrmac ja ha anat al teixit diana i ha interactuat amb les cèl·lules en qüestió, es produeixen deixalles del fàrmac. Aquestes restes continuen circulant per la sang fins a arribar al fetge, que els metabolitza per a expulsar-los per una de les dues vies d’expulsió: (i) la bilis i excreció junt amb els excrements o (ii) la purificació de la sang pels ronyons i la orina.

LA IMPORTÀNCIA DE LA FARMACOGENÈTICA

Un clar exemple de com segons els polimorfismes de la població hi haurà diferent variabilitat de resposta el trobem en els gens transportadors. La glicoproteïna P és una proteïna situada a la membrana de les cèl·lules, que actua com a bomba d’expulsió de xenobiòtics cap a l’exterior de la cèl·lula, és a dir, tots els compostos químics que no formen part de la composició dels organismes vius.

Els humans presentem un polimorfisme que ha estat molt estudiat. Depenent del polimorfisme que posseeixi cada individu, la proteïna transportadora tindrà una activitat normal, intermèdia o baixa.

En una situació normal, la proteïna transportadora produeix una excreció bastant alta del fàrmac. En aquest cas, la persona és portadora de l’al·lel CC (dues citosines). Però si només té una citosina, combinada amb una timina (totes dues són bases pirimidíniques), l’expressió del gen no és tant bona i l’activitat d’expulsió és menor, donant una situació intermèdia. En canvi, si una persona presenta dues timines (TT), l’expressió de la glicoproteïna P a la membrana de la cèl·lula serà baixa. Això suposarà una menor activitat del gen responsable i, conseqüentment, major absorció en sang ja que el fàrmac no és excretat. Aquest polimorfisme, el polimorfisme TT, és perillós pel pacient, ja que passa molt fàrmac a la sang, resultant tòxic pel pacient. Per tant, si el pacient és TT la dosis haurà de ser menor.

Aquest exemple ens demostra que coneixent el genoma de cada individu i com actua segons el seu codi genètic en base a ell, podem saber si l’administració d’un fàrmac a un individu serà l’adequada o no. I en base a això, podem receptar un altre medicament que s’adapti millor a la genètica d’aquesta persona.

APLICACIONS DE LA FARMACOGENÈTICA

Les aplicacions d’aquestes disciplines de la medicina de precisió són moltes. Entre elles es troben optimitzar la dosi, escollir el fàrmac adequat, donar un pronòstic del pacient, diagnosticar-lo, aplicar la teràpia gènica, monitoritzar el progrés d’una persona, desenvolupar nous fàrmacs i predir possibles respostes adverses.

Els progressos que han tingut lloc en la genòmica, el disseny de fàrmacs, teràpies i diagnòstics per a les diferents patologies, han avançat notablement en els últims anys, i han donat pas al naixement d’una medicina més adaptada a les característiques de cada pacient. Ens trobem, per tant, al llindar d’una nova manera d’entendre les malalties i la medicina.

I això es produeix en una època en la que es vol deixar enrere el món de pacients que davant una malaltia o malestar són atesos i diagnosticats de la mateixa manera. Per rutina, se’ls prescriuen els mateixos medicaments i dosis. Per aquest motiu ha sorgit la necessitat d’una alternativa científica que, basada en el codi genètic, ofereix tractar al malalt de manera individualitzada.

REFERÈNCIES

  • Goldstein, DB et al. (2003) Pharmacogenetics goes genomic. Nature Review Genetics 4:937-947
  • Roden, DM et al. (2002) The genetic basis of variability in drug responses. Nature Reviews Drug Discovery 1:37-44
  • Wang, L (2010) Pharmacogenomics: a system approach. Syst Biol Med 2:3-22
  • Ramos, M. et al. (2017) El código genético, el secreto de la vida. RBA Libros
  • Foto portada: Duke Center for Applied Genomics & Precision Medicine

MireiaRamos-catala2

Metal hyperaccumulation in plants

During million years the evolution leaded plants to develop different strategies to defence from natural enemies, giving rise to an evolutionary weaponry war in which the survival of ones and others depends into the ability to beat the other’s adaptations. It is in that scenario where the high-level accumulation of heavy metals in plants plays an important role.

INTRODUCTION

Boyd (2012) commented that plant defences can be grouped in different categories:

  • mechanic: thorns, coverage, etc.
  • chemical: different organic and inorganic components.
  • visual: crypsis and mimicry .
  • behavioural: related with phenology’s modification.
  • and associative: symbiosis with other organisms, such is the case of the genus Cecropia, which has stablished a symbiotic relationship with ants of the genus Azteca, who protects these plants – to know more: Plants and animals can also live in marriage-.

espinas-karyn-christner-flickr
Mechanic defence with thorns (Author: Karyn Christner, Flickr, CC).

It is known that chemical defence is ubiquitous, and thus, a lot of interactions among organisms can be explained for this reason. In this sense, some plants contains high levels of certain chemical elements, frequently metals or metallic components, which plays an important role in the defence, these plants are the heavy metal hyperaccumulating plants.

Heavy metal hyperaccumulating plants and their main characteristics

This plants belong to several families, thus hyperaccumulation is an independent acquisition occurring different times during the evolution. In all cases, hyperaccumulation allowed the ability to grow soils with high levels of heavy metals and to accumulate extraordinary amounts of heavy metals in aerial organs. It is known that the concentration of these chemical elements in hyperaccumulating plants can be 100 – 1000 times higher than in non-hypperaccumulating plants.

Generally, chemistry describes heavy metal as transition metals with atomic mass higher than 20 and with a relative density around 5.  But, from a biological point of view, heavy metals or metalloids are elements which can be toxic in a low concentration. Even though, hyperaccumulating plants has become tolerant, i.e., they hypperacumulate this heavy metals without presenting phytotoxic effects (damage in plant tissues due toxicity).

In this sense, there are three main characteristics typically present in all hyperaccumulating plants:

  • Increased absorption rate of heavy metals.
  • Roots that perform translocation more quickly.
  • Great ability to detoxify and accumulate heavy metals in sheets.

Thus, hyperaccumulating plants are prepared to assimilate, translocate and accumulate high-levels of heavy metals in vacuoles or cellular wall. In part, it is due to the overexpression of genes codifying for membrane transporters.

The threshold values that allow to differentiate a hyperaccumulating plant from a non-hyperaccumulating one are related to the specific phytotoxicity of each heavy metal. According to this criterion, hyperaccumulating plants are plants that when grown on natural soils accumulate in the aerial parts (in grams of dry weight):

  • > 10 mg·g-1 (1%) of Mn or Zn,
  • > 1 mg·g-1 (0,1%) of As, Co, Cr, Cu, Ni, Pb, Sb, Se or Ti
  • or > 0,1 mg·g-1 (0,01%) of Cd.

minuartia-verna-cu-candiru-flickr
Minuartia verna, copper hyperacumulating plant (Autor: Candiru, Flickr, CC).

THE ORIGIN OF HYPERACCULATING PLANTS AND THEIR IMPLICATIONS

Till the moment, several hypothesis has been proposed to explain why certain plants can hyperaccumulate heavy metals:

  • Tolerance and presence of metals in soils.
  • Resistance to drought.
  • Interference with other neighbouring plants.
  • Defence against natural enemies.

The most supported hypothesis is “Elemental defence”, which indicates that certain heavy metals could have a defensive role against natural enemies, such as herbivores and pathogens. So, in the case these organisms consume plants, they should present toxic effects, which would lead them to die or at least to reduce the intake of this plant in future. Even though heavy metals can act through their toxicity, this does not guarantee plants will not be damaged or attacked before the natural enemy is affected by them. For this reason, it is still necessary a more effective defence which allow to avoid the attack.

In contrast, according to a more modern hypothesis, the “Joint effects”, heavy metals could act along with other defensive organic components giving rise to a higher global defence. The advantages of inorganic elements, including heavy metals, are that they are not synthetized by plants, they are absorbed directly from the soil and thus a lower energetic cost is invested in defence, and also they cannot be biodegraded. Even though, some natural enemies can even avoid heavy metal effects by performing the chelation, i.e., using chelators (substances capable of binding with heavy metals to reduce their toxicity) or accumulating them in organs where their activity would be reduced. This modern hypothesis would justify the simultaneous presence of several heavy metals and defensive organic components in the same plant, with the aim to get a higher defence able to affect distinct natural enemies, which would be expected to do not be able to tolerate different element toxicity.

SONY DSC
Thlaspi caerulescens, zinc hyperaccumulating plant (Autor: Randi Hausken, Flickr, CC).

On the other hand, it has been shown that certain herbivores have the ability to avoid the intake of plants with high levels of heavy metals, doing what is called “taste for metals“. Although this is known to occur, the exact mechanism of this alert and avoidance process is still uncertain.

solanum-nigrum-cd-john-tann-flickr
Solanum nigrum, cadmium hyperaccumulating plant (Autor: John Tann, Flickr, CC).

Additionaly, even tough heavy metal concentration in plant are really high, some herbivores manage to surpass this defense by being tolerant, i.e., their diet allows them to intake high dosis of metals and, thus, consume the plant. This could lead to think some herbivores could become specialist in the intake of hyperaccumulating plants, and, thus, this type of defence would be reduced to organisms with varied diets, which are called generalists. It has been demonstrated to not be true, as generalists herbivores sometimes present a higher preference and tolerance for hyperaccumulating plants than specialist organisms.

For all these reasons, it can be said that evolution is still playing an important role in this wonderful weaponry war.

Difusió-anglès

 REFERENCES

  • Boyd, R., Davis, M.A., Wall, M.A. & Balkwill K. (2002). Nickel defends the South African hyperaccumulator Senecio coronatus (Asteraceae) against Helix aspersa (Mollusca: Pulmonidae). Chemoecology 12, p. 91–97.
  • Boyd, R. (2007). The defense hypothesis of elemental hyperaccumulation: status, challenges and new directions. Plant soil 293, p. 153-176.
  • Boyd, R. (2012). Elemental Defenses of Plants by Metals. Nature Education Knowledge 3 (10), p. 57.
  • Laskowski, R. & Hopkin, S.P. (1996). Effect of Zn, Cu, Pb and Cd on Fitness in Snails (Helix aspersa). Ecotoxicology and environmentak safety 34, p. 59-69.
  • Marschner, P. (2012). Mineral Nutrition of Higher Plants (3). Chennai: Academic Press.
  • Noret, N., Meerts, P., Tolrà, R., Poschenrieder, C., Barceló, J. & Escarre, J. (2005). Palatability of Thlaspi caerulescens for snails: influence of zinc and glucosinolates. New Phytologist 165, p. 763-772.
  • Prasad, A.K.V.S.K. & Saradhi P.P. (1994).Effect of zinc on free radicals and proline in Brassica and Cajanus. Phytochemistry 39, p. 45-47.
  • Rascio, N. & Navari-Izzo, F. (2011). Heavy metal hyperaccumulating plants: How and why do they do it? And what makes them so interesting?. Plant Science 180 (2),p. 169-181.
  • Shiojiri, K., Takabayashi, J., Yano, S. & Takafuji, A. (2000) Herbivore-species-specific interactions between crucifer plants and parasitic wasps (Hymenoptera: Braconidae) that are mediated by infochemicals present in areas damaged by herbivores. Applied Entomology and Zoology 35, p. 519–524.
  • Solanki, R. & Dhankhar, R. (2011). Biochemical changes and adaptive strategies of plants under heavy metal stress. Biologia 66 (2), p. 195-204.
  • Verbruggen, N., Hermans, C. & Schat, H. (2009). Molecular mechanisms of metal hyperaccumulation in plants. New Phytologist 181 (4), p. 759–776.
  • Wenzel, W.W. & Jockwer F. (1999). Accumulation of heavy metals in plants grown on mineralised soils of the Austrian Alps. Environmental pollution 104, p. 145-155.

Danger, poisonous mammals!

We usually associate snakes, spiders, jellyfish, etc. as venomous animals par excellence, but did you know that there are poisonous mammals? In this article we will discover who are they and the nature and use of their poisons.

THE PLATYPUS

The platypus (Ornithorhynchus anatinus) is the most famous among the poisonous mammals, and not just for this feature. With a peak like a duck and oviparous (laying eggs), when it was discovered some scientists thought it was a fraud.

platypus ornitorrinco ornitorinc
Platypus (Ornithorhynchus anatinus). Photo by Jonathan Munro

They belong to the order monotremes, which means “one hole” in reference to the cloaca, the end of the digestive and reproductive systems. Some evolutionary biologists refer to them as the “missing linkbetween reptiles and mammals, as they have characteristics of both groups. Monotremes are the only mammals that lay eggs, but his body is covered with hair and the young are fed with breast milk. They are distributed by Australia, Tasmania and New Guinea.

Platypuses have a spur on the hind legs, which only in the case of males, release poison produced by femoral glands (located in the leg). The male uses it mainly to defend their territory and establish their dominance during the mating season, although if it is bothered also uses it as a defense. This poison can kill small animals, including dogs, and cause severe pain and swelling in humans. This pain can last days or months.

Platypus spur, espolón ornitorrinco
Spur on the hind leg of a platypus. Photo by E. Lonnon

Toxins are four proteins, three of which are unique to the platypus. They are like the defensins (DLP, defensin-like proteins). These are globular proteins, small and compacted, involved in the activation of pain receptors. Understanding how these toxins act it has special interest because they cause a lasting and severe pain; it may open new chances in the synthesis of analgesic drugs.

short-beaked echidna, equidna de nariz corta, equidna de nas curt
Short-beake echidna (Tachyglossus aculeatus). Photo de Tony Britt-Lewis

Echidnas (family Tachyglossidae) complete the order of monotremes with the platypus; consequently they are also oviparous. The family consists of four species, with the common characteristic of having the body covered with dense hair and spines. They are mainly insectivores specializing in ants and termites.

Like the platypus, they also have spurs behind the knees, but their secretions are not poisonous. The substances are used to mark their territory, according to the recent studies.

SLOW LORIS

As we saw in a previous post, lorises are primates in the prosimians suborder. They are nocturnal, arboreal and feed primarily on insects, vegetables and fruits. The slow lorises (Nycticebus) living in Southeast Asia, are the only poisonous primate. They possess poison glands on the elbows (brachial gland), and poison their body with arms and tongue, which can also join saliva and be transmitted by bitting.

lori pigmeo, nycticebus pigmaeus,
Pygmy slow loris (Nycticebus pigmaeus). Photo by Ch’ien C. Lee

In this case the poison is used as a defense against predators, causing them pain, inflammation, necrosis (cell death) in the area of the bite, hematuria (blood in urine) or in some cases anaphylactic shock (allergic reaction) which can lead to death, even in humans (some are threatened by the illegal pet trade and traditional Chinese medicine). The poison also serves as protection for the young, they are licked by their parents and the poisonous secretion is distributed throughout the coat. Being poisonous, unusual among primates, can help counteract the disadvantages of its slow movements. Exudate from glands, as in echidnas, can also give olfactory information of range and territory between individuals of loris (Hagey et al., 2007).

Loris de Kayan (Nycticebus kayan). foto de Ch'ien C. Lee
Kayan loris (Nycticebus kayan). Photo by Ch’ien C. Lee

Toxins are polypeptides (generated when glandular secretion is mixed with saliva) and an unidentified steroid. Secretion is similar to the allergen Fel d 1 which is in the domestic cat and cause allergies in humans (Hagey et al., 2006; Krane et al., 2003).

It is believed that slow lorises even have converged evolutionarily with cobras, for his defensive behavior when threatened, whistling and raising his arms around his head. (Nekaris et. al, 2003).

Loris, cobras, evolucion, convergencia
Mimicry between loris and cobras. 1. Javan slow loris, 2 y 3. Spectacled cobra, 4. Bengal slow loris. Photo by Nekaris et. al.

In the following video a lazy lori is disturbed and hisses like a snake while trying to bite:

SOLENODON OR ALMIQUI

They are small and nocturnal mammals, basically insectivores, that live in the West Indies. The Hispaniolan solenodon (Solenodon paradoxus), also known as the Dominican solenodon, Haitian solenodon or agouta, lives on the island de La Española (Dominican Republic and Haiti) while The Cuban solenodon or almiqui (Solenodon cubanus) is distributed throughout Cuba. They are considered living fossils because they have similar characteristics to primitive mammals of the end of the Mesozoic Era (kingdom of the dinosaurs).

solenodonte de La Española (Solenodon paradoxus
Hispaniolan solenodon (Solenodon paradoxus). Photo by Eladio M. Fernández.

Unlike other poisonous mammals, toxic saliva is produced under the jaw (submandibular glands), which is transported by pipes to the front of the mouth. The second incisor teeth have a groove where toxic saliva accumulates to promote their entry into the wounds. They are the only mammals that inject venom through its teeth, similar to the way snakes do.

diente, solenodon, teeth, surco
Paradoxus Solenodon lower jaw incisor showing the groove. Photo by Phil Myers

The main function of this venom is to immobilize prey, as well as insects they can hunt small vertebrates such as reptiles, amphibians and birds.

Almiquí, Cuba, Solenodon, cubanus, Cuban giant shrew
Cuban solenodon (Solenodon cubanus). Photo by Julio Genaro.

This poison may have been developed to keep alive but immobilized prey during times of shortage, to aid in digestion, minimize energy expenditure in the struggle for hunting and face prey even twice as big as them. This venom is not deadly to humans.

SHREWS

The northern short-tailed shrew (Blarina brevicauda), the Eurasian water shrew (Neomys fodiens) and the Mediterranean water shrew (Neomys anomalus) also have submandibular glands similar to solenodons. They are distributed by North America (northern short-tailed shrew) and Europe and Asia (water shrews), including the Iberian Peninsula.

Musaraña colicorta americana (Blarina brevicauda). Foto de Gilles Gonthier.
The northern short-tailed shrew (Blarina brevicauda). Photo by Gilles Gonthier.

The short-tailed shrew can consume up to three times its weight in food per day. Their saliva is the most poisonous and uses it to paralyze their prey, to eat them or keep them alive in times of shortage. The water shrews also store its immobilized prey under rocks.

Musgaño (Neomys anomalus). Foto de rollin Verlinde.
Mediterranean water shrew (Neomys anomalus). Photo by Rollin Verlinde.

These animals attack from behind and bite the neck of its prey so that the poison acts more quickly, affecting the central nervous system (neurotoxins). The respiratory and vascular system is also affected and causes seizures, incoordination, paralysis and even death of small vertebrates.

Musgaño patiblanco-Neomys_fodiens, Wasserspitzmaus
Eurasian water shrew (Neomys fodiens). Photo by R. Altenkamp.

Its teeth don’t have grooves as the solenodons do, but a concave surface to store the toxic saliva.

neomys, anomalus, mandibula, dientes, veneno
Lower jaw of Neomys anomalus. Photo by António Pena.

It is suspected that other mammals also produce toxic saliva similarly, as the European mole (Talpa europaea) and other species of shrew, but there are no conclusive studies.

MANED RAT

The maned rat or crested rat (Lophiomys imhausi), lives in Africa and  uses his poisoned hair to protect themself from predators.

Rata crestada Lophiomys_imhausi, rata de crin, maned rat
Maned rat (Lophiomys imhausi). Photo by Kevin Deacon

Unlike other mammals that produce their own poison, the crested rat gets toxin (called ouabain) from the bark and roots of a tree (Acokanthera schimperi). Chews the bark and the mixture of saliva and toxins are distributed on the body. Their hairs are cylindrical whith a perforated microscopic structure, which favors the absorption of venom. In case of danger, it bristles and shows his brown coat with white stripes, warning of its potential danger. This strategy of persuasion based on brightly colored warning is known as aposematism present in many animals, such as bees.

In this BBC video you can see a crested rat and a hair under the microscope absorbing ink, showing its porous structure:

It is unknown how it is immune to the toxin, since it is the same substance used by some African tribes for hunting such large animals like elephants.

Ouabain is a glycoside which controls the heartbeat, causing infarcts if absorbed in large quantities. The study of the mechanisms that protect the crested rat of a substance that regulates the heartbeat, can help develop treatments for heart problems.

European hedgehogs (Erinaceus europaeus) have similar behavior (smearing the body with foreign poison), but it is not established whether the objective is defensive because it does not scare away predators.

In conclusion, strategies, practices and nature of the poison in mammals are varied and their study may have important medical implications for drug development and increase awareness of the evolutionary relationships between different groups of living animals (reptiles-mammals) and their ancestors.

REFERENCIAS

MIREIA QUEROL ALL YOU NEED IS BIOLOGY

Perill, mamífers verinosos!

Normalment associem a les serps, aràcnids, meduses, etc. com els animals verinosos per excel·lència, però sabies que també hi ha mamífers verinosos? En aquest article descobrirem quins són i la natura i ús dels seus verins.

L’ORNITORINC

L’ornitorinc (Ornithorhynchus anatinus) és el més famós entre els mamífers verinosos, i no només per aquesta característica. Amb un bec semblant a un ànec i reproducció ovípara (que posa ous), quan va ser descobert alguns científics pensaven que era un frau.

platypus ornitorrinco ornitorinc
Ornitorinc (Ornithorhynchus anatinus). Foto de Jonathan Munro

Pertanyen a l’ordre dels monotremes, que significa lieralment un sol orificien al·lusió a la cloaca, el final de l’aparell digestiu i reproductor. Alguns biòlegs evolutius es refereixen a ells com la “baula perdudaentre rèptils i mamífers, ja que presenten característiques d’ambdós grups. Els monotremes són els únics mamífers que posen ous, però el seu cos està cobert de pèl i les cries s’alimenten de la llet materna. Es distribueixen per Austràlia, Tasmània i Nova Guinea.

Els ornitorincs tenen un esperó a les potes del darrere, que només en el cas dels mascles, allibera verí produït per les glàndules crurals (situades a la cama). El mascle ho utilitza principalment per defensar el seu territori i establir la seva dominància durant l’època d’aparellament, encara que si és molestat també el fa servir com a defensa. Aquest verí és capaç de matar animals petits, fins i tot a gossos, i provocar un dolor intens i inflamació en els humans. Aquest dolor pot durar dies o mesos segons el cas.

Platypus spur, espolón ornitorrinco
Esperó a la pota del darrere d’un ornitorinc. Foto de E. Lonnon

Les toxines són quatre proteïnes, tres de les quals són exclusives de l’ornitorinc. Són semblants a les defensines (DLP, defensinlike proteins). Es tracta de proteïnes de tipus globular, petites i compactades, que participen en l’activació dels receptors del dolor. El coneixement de com actuen aquestes toxines, d’especial interès perquè provoquen un dolor durador i intens, pot obrir noves vies en la síntesi de fàrmacs analgèsics.

short-beaked echidna, equidna de nariz corta, equidna de nas curt
Equidna de nas curt (Tachyglossus aculeatus). Foto de Tony Britt-Lewis

Els equidnes (família Tachyglossidae) completen l’ordre dels monotremes juntament amb l’ornitorinc; en conseqüència també són ovípars. La família està formada per quatre espècies, amb la característica comuna de tenir el cos cobert de pèl dens i espines. Són principalment insectívors especialitzats en formigues i tèrmits (mirmecòfags).

Igual que els ornitorincs, també posseeixen esperons darrere dels genolls, però les seves secrecions no són verinoses. Les utilitzen com a substàncies per marcar el seu territori, segons els  últims estudis.

LORIS PERESOSOS

Com vam veure en un article anterior, els loris són primats del subordre dels prosimis. Són nocturns, arborícoles i s’alimenten principalment d’insectes, vegetals i fruites. Els loris peresosos (gènere Nycticebus), originaris del sud-est asiàtic, són els únics primats verinosos. Posseeixen glàndules verinoses als colzes (glàndula braquial), i es distribueixen el verí pel cos amb els braços i la llengua, el qual també pot unir-se a la saliva i transmetre‘s per mossegades.

lori pigmeo, nycticebus pigmaeus,
Loris pigmeu (Nycticebus pigmaeus). Foto de Ch’ien C. Lee

En aquest cas el verí és utilitzat com a defensa davant els seus depredadors, el que els provoca dolor, inflamació, necrosi (mort cel·lular) a la zona de la mossegada, hematúria (sang en orina) o en alguns casos xocs anafilàctics (reacció al·lèrgica) que poden conduir a la mort, fins i tot en humans (alguns estan amenaçats per la seva comercialització il·legal com a mascotes i en la medicina tradicional xinesa). El verí també serveix de protecció per a les cries, ja que en ser llepades pels seus progenitors la secreció verinosa es distribueix per tot el pelatge. El fet de ser verinosos, insòlit dins dels primats, pot ajudar a contrarestar els desavantatges dels seus lents moviments. L’exsudat de les glàndules, igual que en els equidnes, també pot donar informació olfactiva de rang i territori entre individus de loris (Hagey et al., 2007).

Loris de Kayan (Nycticebus kayan). foto de Ch'ien C. Lee
Loris de Kayan (Nycticebus kayan). Foto de Ch’ien C. Lee

Les toxines són de tipus polipeptídic (que es generen en barrejar la secreció glandular amb la saliva) i un esteroide no identificat. La secreció és semblant a l’al·lergen Fel d 1, que es troba en el gat domèstic i provoca al·lèrgies en humans (Hagey et al., 2006; Krane et al., 2003).

Es creu fins i tot que els loris mandrosos han convergit evolutivament amb les cobres, pel seu comportament defensiu quan es troben amenaçats, xiulant i aixecant els braços al voltant del seu cap (Nekaris et. al, 2003).

Loris, cobras, evolucion, convergencia
Mimetisme entre loris i cobres. 1. Lori de Java, 2 y 3. Cobra india 4. Lori de Bengala. Foto de Nekaris et. al.

En el següent vídeo una lori peresós és molestat i xiula com una serp mentre tracta de mossegar:

 EL SOLENODONT O ALMIQUÍ

Es tracta de petits mamífers nocturns semblants a les musaranyes i bàsicament insectívors que habiten a les Antilles. El solenodont de La Española (Solenodon paradoxus) habita a l’illa del mateix nom (República Dominicana i Haití) mentre que l’almiquí de Cuba (Solenodon cubanus) es distribueix per Cuba. Se’ls considera fòssils vivents ja que presenten característiques primitives similars a les que posseïen els mamífers del final de l’Era Secundària (regnat dels dinosaures).

solenodonte de La Española (Solenodon paradoxus
Solenodont de La Española (Solenodon paradoxus). Foto de Eladio M. Fernández.

A diferència de la resta de mamífers verinosos, la saliva tòxica es produeix en unes glàndules sota de la mandíbula (glàndules submaxil·lars), que és transportada per conductes cap a la part davantera de la boca. Les segons dents incisives tenen un solc on s’acumula la saliva tòxica per afavorir la seva entrada a les ferides. Són doncs els únics mamífers que injecten verí a través de les seves dents, de manera similar a les serps.

diente, solenodon, teeth, surco
Mandíbula inferior de Solenodon paradoxus on es veu el solc de l’incisiu. Foto de Phil Myers

La principal funció d’aquest verí és immobilitzar les preses que cacen, ja que a més d’insectes poden atrapar petits vertebrats com rèptils, amfibis o aus.

Almiquí, Cuba, Solenodon, cubanus, Cuban giant shrew
Almiquí de Cuba (Solenodon cubanus). Foto de Julio Genaro.

Evolutivament, aquest verí pot haver-se desenvolupat per mantenir preses vives però immòbils durant èpoques d’escassetat, per ajudar en la digestió, minimitzar la despesa d’energia en la lluita durant la caça i enfrontar-se a preses fins i tot el doble de grans que ells. Aquest verí no és mortal per als humans.

MUSARANYES

La musaranya cuacurta septendrional (Blarina brevicauda), la musaranya aquàtica pirinenca (Neomys fodiens) i la musaranya aquàtica mediterrània (Neomys anomalus) també posseeixen glàndules submaxil·lars com el solenodont. Es distribueixen per Amèrica del Nord (musaranya cuacurta) i Europa i Àsia (musaranyes aquàtiques), inclosa la Península Ibèrica.

Musaraña colicorta americana (Blarina brevicauda). Foto de Gilles Gonthier.
Musaranya cuacurta septentrional (Blarina brevicauda). Foto de Gilles Gonthier.

La musaranya cuacurta pot consumir fins a tres vegades el seu pes d’aliment al dia. La seva saliva és la més verinosa que existeix i la fa servir per paralitzar a les seves preses, per menjar-les o conservar-les vives en períodes d’escassetat. Les musaranyes aquàtiques també emmagatzemen les seves preses immobilitzades sota de les roques.

Musgaño (Neomys anomalus). Foto de rollin Verlinde.
Musaranya aquàtica mediterrània (Neomys anomalus). Foto de Rollin Verlinde.

Aquests animals ataquen des del darrere i mosseguen el coll de les seves preses perquè el verí actuï més ràpidament, ja que afecta el sistema nerviós central (neurotoxines). L’aparell respiratori i vascular també resulta afectat i produeix convulsions, descoordinació de moviments, paràlisi i fins i tot la mort de petits vertebrats.

Musgaño patiblanco-Neomys_fodiens, Wasserspitzmaus
Musaranya aquàtica pirinenca (Neomys fodiens). Foto de R. Altenkamp.

Les seves dents no tenen solcs com els dels solenodonts, però sí una superfície còncava per emmagatzemar la saliva tòxica.

neomys, anomalus, mandibula, dientes, veneno
Mandíbula inferior de Neomys anomalus. Foto de António Pena.

Se sospita que altres mamífers produeixen també saliva tòxica de manera similar, com el talp europeu (Talpa europaea) i altres espècies de musaranya, però no es disposa d’estudis concloents.

RATA CRESTADA AFRICANA

També coneguda com rata de crinera (Lophiomys imhausi), la rata crestada africana utilitza verí present al seu pèl per protegir-se dels seus depredadors.

Rata crestada Lophiomys_imhausi, rata de crin, maned rat
Rata crestada africana (Lophiomys imhausi). Foto de Kevin Deacon

A diferència de la resta de mamífers que produeixen els seus propis verins, la rata crestada africana obté la toxina (anomenada ouabaína) de l’escorça i arrels d’un arbre (acocantera o llorer tòxic, Acokanthera schimperi). Els mastega i s’unta la barreja de saliva i tòxic al cos. Els seus pèls tenen una estructura microscòpica cilíndrica perforada, el que afavoreix l’absorció del verí. En cas de perill, s’estarrufa i mostra el seu pelatge marró a ratlles blanques, advertint del seu perill potencial. Aquesta estratègia de persuasió basada en colors cridaners d’advertència es coneix com aposematisme, present en molts animals, com les abelles.

En aquest vídeo de la BBC online s’observa una rata crestada i imatges al microscopi d’un pèl absorbint tinta, mostrant la seva estructura porosa:

Es desconeix de quina manera és immune a la toxina, ja que és la mateixa substància que fan servir algunes tribus africanes per caçar animals tan grans com l’elefant. La ouabaína és un glucòsid que controla el batec del cor, provocant infarts si s’absorbeix en grans quantitats. L’estudi dels mecanismes que protegeixen la rata crestada d’una substància que regula el ritme cardíac, pot ajudar al desenvolupament de tractaments per a problemes cardíacs.

Els eriçons europeus (Erinaceus europaeus) tenen un comportament similar (empastifar-se el cos amb verí aliè), però no s’ha pogut comprovar si l’objectiu és defensiu ja que no espanta als depredadors.

En conclusió, les estratègies, usos i natures del verí en mamífers són variades i el seu estudi pot tenir importants conseqüències mèdiques en el desenvolupament de fàrmacs, així com augmentar el coneixement de les relacions evolutives entre diferents grups d’animals actuals (rèptils-mamífers) i seus avantpassats.

REFERÈNCIES

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