Document Type

Article

Publication Date

1-2019

Publication Title

Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology

Volume

215

Publisher

Elsevier

DOI

https://doi.org/10.1016/j.cbpc.2018.09.003

Abstract

While it has been known for a while that some snake species are extremely sensitive to acetaminophen, the underlying mechanism for this toxicity has not been reported. To investigate if essential detoxification enzymes are missing in snake species that are responsible for biotransformation of acetaminophen in other vertebrate species, livers were collected from a variety of snake species, together with samples from alligator, snapping turtle, cat, rat, and cattle. Subcellular fractions were analyzed for enzymatic activities of phenol-type sulfotransferase and UDP‑glucuronosyltransferase, total glutathione S‑transferase, and N‑acetyltransferase. The results showed that none of the snake species, together with the cat samples, had any phenol-type glucuronidation activity, and that this activity was much lower in alligator and turtle samples than in the mammalian species. Combined with the lack of N‑acetyltransferase activity in snakes and cats, this would explain the accumulation of the aminophenol metabolite, which induces methemoglobinemia and subsequent suffocation of snakes and cats after acetaminophen exposure. While previous investigations have concluded that in cats the gene for the phenol-type glucuronosyltransferase isoform has turned into a pseudogene because of several point mutations, evaluation of genomic information for snake species revealed that they have only 2 genes that may code for glucuronosyltransferase isoforms. Similarity of these genes with mammalian genes is <50%, and suggests that the expressed enzymes may act on other types of substrates than aromatic amines. This indicates that the extreme sensitivity for acetaminophen in snakes is based on a different phylogenetic origin than the sensitivity observed in cats.

Comments

This manuscript has been published in Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology. Please find the published version here (note that a subscription is necessary to access this version):

https://www.sciencedirect.com/science/article/pii/S1532045618301315?via%3Dihub

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