75 research outputs found
Cadmium Exposure and Neurodevelopmental Outcomes in U.S. Children
Background: Low-level environmental cadmium exposure in children may be associated with adverse neurodevelopmental outcomes
Impacto da suplementação de vitamina C sobre nĂveis de peroxidação lipĂdica e glutationa reduzida em tecido hepático de camundongos com imunossupressĂŁo induzida por ciclofosfamida
The use of antipyrine clearance to measure liver damage in psoriatic patients receiving methotrexate
The Interaction Between Selenium Status, Sex Hormones, and Thyroid Metabolism in Adolescent Girls in the Luteal Phase of their Menstrual Cycle
Pharmacokinetics of dexmedetomidine administered intravenously in isoflurane-anesthetized cats
Evolution of a major drug metabolizing enzyme defect in the domestic cat and other felidae: phylogenetic timing and the role of hypercarnivory
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
Effects of estradiol benzoate and progesterone on superoxide dismutase activity in the rat liver
Mitigation of oxidative stress in cyclophosphamide-challenged hepatic tissue by DL-α-lipoic acid
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