Species variations in the metabolism of phenol

Capel, Ifor D.; French, Michael R.; Millburn, Peter; Smith, Robert L.; Williams, R. T.

doi:10.1042/bj1270025pb

Cited by 18 publications

(5 citation statements)

References 6 publications

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“…Cats and other felidae are known for their low capacity for glucuronide conjugation of drugs and toxins. This assumption is based on early data on the biotransformation of phenolic compounds in cats in comparison with other species (Capel et al ., ,b, ). Subsequently, acetaminophen (paracetamol, a phenolic derivative) is the most prominent example of a drug that is toxic for cats, when common dosage regimens established for dogs or humans are applied.…”

Section: Introductionmentioning

confidence: 99%

Comparing the glucuronidation capacity of the feline liver with substrate‐specific glucuronidation in dogs

Beusekom

Fink‐Gremmels

Schrickx

2013

Vet Pharm & Therapeutics

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This study aimed to assess the overall glucuronidation capacity of cats, using prototypic substrates identified for human UDP-glucuronosyltransferases (UGTs). To this end, Michaelis-Menten kinetics were established for the substrates using feline hepatic microsomal fractions, and results were compared with similar experiments carried out with dog liver microsomes. Cats are known for their low capacity of glucuronide formation, and UGT1A6 was found to be a pseudogene. However, functional studies with typical substrates were not performed and knowledge of the enzymology and genetics of other glucuronidation enzymes in felidae is lacking. The results of this study showed extremely low formation of naphthol-1-glucuronide (1.7 ± 0.4 nmol/mg protein/min), estradiol-17-glucuronide (<0.7 nmol/mg protein/min), and morphine-3-glucuronide (0.2 ± 0.03 nmol/mg protein/min), suggesting a lack of functional UGT1A6 and UGT2B7 homologues in the cat's liver. Dog liver microsomes were producing these glucuronides in much higher amounts. Glucuronide capacity was present for the substrates 17β-estradiol (estradiol-3-glucuronide, 2.9 ± 0.2 nmol/mg protein/min) and 4-methylumbelliferone (31.3 ± 3.3 nmol/mg protein/min), assuming that cats have functional homologue enzymes to at least the human UGT1A1 and probably other UGT1A isozymes. This implies that for new drugs, glucuronidation capacity has to be investigated on a substance-to-substance base. Knowledge of the glucuronidation rate of a drug provides the basis for pharmacokinetic modeling and as a result proper dosage regimens can be established to avoid undesirable drug toxicity in cats.

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Section: Introductionmentioning

confidence: 99%

Comparing the glucuronidation capacity of the feline liver with substrate‐specific glucuronidation in dogs

Beusekom

Fink‐Gremmels

Schrickx

2013

Vet Pharm & Therapeutics

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“…Seule une petite fraction du phénol est transformée en catéchol ou en hydroquinone [17]. Le phénol est essentiellement éliminé par voie urinaire [18]. Cependant, il existe une corrélation entre les concentrations urinaires en phénol et l'exposition humaine.…”

Section: Fig3 Variation Du Poids Corporel Des Animaux Durant La Pérunclassified

Evaluation of the Leave and Bud Decoctions Pinus Halepensis Mill Effects on the Induced-Phenol Renal Toxicity in Wistar Rats

Berroukche¹,

Amara

Halimi³

et al. 2015

J. Fundam and Appl Sci.

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Pinus halepensis M. (Pinaceae) has done object many indications in traditional medicine.Several studies have demonstrated a protective activity of essential oils extracted from various plant species against renal toxicity induced by chemicals in the animal model. The objective of this study is to assess the anti toxic effects of decocted leaves and buds of Pinus halepensis M. on Wistar rats initially exposed to phenol C6H5OH (180 mg / kg body weight). The results of laboratory analyzes of biochemical parameters revealed that decocted leaves and buds (250 mg / kg body weight) have shown a highly significant antitoxic activity (p < 0,001). The protective effect of decocted leaves and buds were respectively expressed by a decrease in serum concentrations of biochemical markers urea ( 0,32 and 0,28 g/l) and

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“…Profound interspecies, as well as intraspecies differences have been revealed for absorption [129][130][131][132][133][134], distribution [107,135], metabolism [136][137][138][139][140][141][142][143][144][145][146], elimination [147,148], and toxicity [38,88,127,134,[149][150][151][152][153][154][155][156][157]. Collectively, absorption, distribution, metabolism, elimination and Litchfield conducted a study in 1962 (see Table 2) comparing toxicity in humans with toxicity in rats and dogs.…”

Section: Interspecies Differencesmentioning

confidence: 99%

Animal Models in an Age of Personalized Medicine

Greek¹,

Menache²,

Rice

2011

Personalized Medicine

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Personalized medicine is based on intraspecies differences. It is axiomatic that small differences in genetic make-up can result in dramatic differences in response to drugs or disease. To express this in more general terms: in any given complex system, small changes in initial conditions can result in dramatically different outcomes. Despite human variability and intraspecies variation in other species, nonhuman species are still the primary model for ascertaining data for humans. We call this practice into question and conclude that human-based research should be the primary means for obtaining data about human diseases and responses to drugs.

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Species variations in the metabolism of phenol

Cited by 18 publications

References 6 publications

Comparing the glucuronidation capacity of the feline liver with substrate‐specific glucuronidation in dogs

Comparing the glucuronidation capacity of the feline liver with substrate‐specific glucuronidation in dogs

Evaluation of the Leave and Bud Decoctions Pinus Halepensis Mill Effects on the Induced-Phenol Renal Toxicity in Wistar Rats

Animal Models in an Age of Personalized Medicine

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