Conjugation of foreign compounds in the elephant and hyaena

Caldwell, John; French, Michael R.; Idle, Jeffrey R.; Renwick, A.G.; Bassir, O.; Williams, R. T.

doi:10.1016/0014-5793(75)80756-3

Cited by 8 publications

(4 citation statements)

References 12 publications

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“…While previous studies indicated that phenolic glucuronidation was undetectable in African civet and spotted hyena [10], [12], our results suggest that this phenotype is not a consequence of adverse mutations in the UGT1A6 coding region of these hypercarnivorous species. We have previously shown that acetaminophen glucuronidation by domestic ferret liver is also quite low, although ferret UGT1A6 contains no reading frame errors [28].…”

Section: Discussioncontrasting

confidence: 75%

“…However, as yet it is not known whether this represents a single UGT1A6 pseudogenization event affecting one particular lineage, or whether multiple independent UGT1A6 inactivations have occurred either within or beyond the Felidae. In a classical series of radiotracer experiments conducted nearly 40 years ago, glucuronidation of orally administered [ 14C ]phenol was found to be deficient in several other families of Carnivora including Viverridae (African civet, forest genet), Hyaenidae (spotted hyena), in addition to all Felidae species examined (African lion, caracal, and domestic cat) [3], [10], [11], [12]. These findings suggested either a more ancient origin of UGT1A6 loss predating Felidae divergence, or perhaps more recent multiple UGT1A6 inactivations.…”

Section: Introductionmentioning

confidence: 99%

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Evolution of a Major Drug Metabolizing Enzyme Defect in the Domestic Cat and Other Felidae: Phylogenetic Timing and the Role of Hypercarnivory

et al. 2011

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The domestic cat (Felis catus) shows remarkable sensitivity to the adverse effects of phenolic drugs, including acetaminophen and aspirin, as well as structurally-related toxicants found in the diet and environment. This idiosyncrasy results from pseudogenization of the gene encoding UDP-glucuronosyltransferase (UGT) 1A6, the major species-conserved phenol detoxification enzyme. Here, we established the phylogenetic timing of disruptive UGT1A6 mutations and explored the hypothesis that gene inactivation in cats was enabled by minimal exposure to plant-derived toxicants. Fixation of the UGT1A6 pseudogene was estimated to have occurred between 35 and 11 million years ago with all extant Felidae having dysfunctional UGT1A6. Out of 22 additional taxa sampled, representative of most Carnivora families, only brown hyena (Parahyaena brunnea) and northern elephant seal (Mirounga angustirostris) showed inactivating UGT1A6 mutations. A comprehensive literature review of the natural diet of the sampled taxa indicated that all species with defective UGT1A6 were hypercarnivores (>70% dietary animal matter). Furthermore those species with UGT1A6 defects showed evidence for reduced amino acid constraint (increased dN/dS ratios approaching the neutral selection value of 1.0) as compared with species with intact UGT1A6. In contrast, there was no evidence for reduced amino acid constraint for these same species within UGT1A1, the gene encoding the enzyme responsible for detoxification of endogenously generated bilirubin. Our results provide the first evidence suggesting that diet may have played a permissive role in the devolution of a mammalian drug metabolizing enzyme. Further work is needed to establish whether these preliminary findings can be generalized to all Carnivora.

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Section: Discussioncontrasting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Evolution of a Major Drug Metabolizing Enzyme Defect in the Domestic Cat and Other Felidae: Phylogenetic Timing and the Role of Hypercarnivory

et al. 2011

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“…We have found that both 14C-labelled benzoic acid and phenylacetic acid fed at a level of 100 mg/kg to a young female African elephant are excreted in the urine mainly as hippuric acid (90% of excreted 14C) and phenaceturic acid (87%), respectively (see Tables 4 and 5). On administration of [l4C] phenol to the same animal, the urinar-y metabolites were found to be phenylsulphate (73% of excreted 14C), phenylglucuronide (25%) and quinol sulphate (1%) (14). These limited studies indicate nothing unusual in the metabolism of these substances by the African elephant.…”

Section: Studies On the Elephantmentioning

confidence: 83%

“…Although this could be due to slow excretion of the compounds, it is probably due to incomplete recovery of excreta. Since there are difficulties in working with large, dangerous animals, the rather crude techniques employed are necessary under the circumstances (14).…”

Section: Conjugation Reactions In Carnivoresmentioning

confidence: 99%

Drug metabolism in ”exotic” animals

Caldwell

Bassir

et al. 1978

European Journal of Drug Metabolism and Pharmacokinetics

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Most studies of foreign compound metabolism have been performed in a restricted number of common laboratory animal species. The examination of animals not commonly found in the laboratory may aid in understanding the effects of environmental chemicals on wild animals and in the search for better animal models for human drug metabolism. We have performed a number of studies in "exotic" animals, such as the lion, civet, genet, hyena, elephant, various bats and reptiles, and this review compares the findings with those in common laboratory animals, to explore the possibility that drug metabolism studies may aid in the zoological classification of animals.

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Serum concentration of inorganic sulfate in mammals: Species differences and circadian rhythm

Krijgsheld

1980

Comparative Biochemistry and Physiology Part A: Physiology

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Conjugation of foreign compounds in the elephant and hyaena

Cited by 8 publications

References 12 publications

Evolution of a Major Drug Metabolizing Enzyme Defect in the Domestic Cat and Other Felidae: Phylogenetic Timing and the Role of Hypercarnivory

Evolution of a Major Drug Metabolizing Enzyme Defect in the Domestic Cat and Other Felidae: Phylogenetic Timing and the Role of Hypercarnivory

Drug metabolism in ”exotic” animals

Serum concentration of inorganic sulfate in mammals: Species differences and circadian rhythm

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