2006
DOI: 10.1124/dmd.105.006601
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Effect of Chronic Renal Insufficiency on Hepatic and Renal Udp-Glucuronyltransferases in Rats

Abstract: ABSTRACT:Significant evidence exists regarding altered CYP450 enzymes in chronic renal insufficiency (CRI), although none exists for the phase II enzymes. The objective of this study was to investigate the effect of CRI on hepatic and renal UDP-glucuronyltransferase (UGT) enzymes. Three groups of rats were included: CRI induced by the 5/6th nephrectomy model, control, and control pair-fed (CPF) rats. UGT activities were determined in liver and kidney microsomes by the 3-and 17-glucuronidation of ␤-estradiol (E… Show more

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Cited by 32 publications
(23 citation statements)
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References 34 publications
(36 reference statements)
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“…25) Thus, it is reasonable to suppose that the 3-PBA excretion rate might change depending on population-and gender-related differences in the expression and activity of the carboxylesterase, ADH, ALDH, CYP and UDP-glucuronosyltransferase isozymes in the liver and other organs, as suggested from experimental studies. [26][27][28][29][30][31][32][33] So far, there are few human data on the toxicokinetics of PYRs. When cypermethrin was administered orally to male human volunteers as a single dose of 8 mmol, about 1.6 mmol 3-PBA and 4.3 mmol DCCA (sum of free and glucuronide forms) were excreted in urine by 120 h after administration.…”
Section: Toxicokinetics Of Pyr In Humansmentioning
confidence: 99%
“…25) Thus, it is reasonable to suppose that the 3-PBA excretion rate might change depending on population-and gender-related differences in the expression and activity of the carboxylesterase, ADH, ALDH, CYP and UDP-glucuronosyltransferase isozymes in the liver and other organs, as suggested from experimental studies. [26][27][28][29][30][31][32][33] So far, there are few human data on the toxicokinetics of PYRs. When cypermethrin was administered orally to male human volunteers as a single dose of 8 mmol, about 1.6 mmol 3-PBA and 4.3 mmol DCCA (sum of free and glucuronide forms) were excreted in urine by 120 h after administration.…”
Section: Toxicokinetics Of Pyr In Humansmentioning
confidence: 99%
“…15) Ugt2b2 and Ugt2b3 have been reported to be highly expressed in the liver, 16) suggesting that these isoforms may be associated with E17G formation in rat liver. Ugt1a2 mRNA was not expressed in the liver or kidney but was found predominantly in the small intestine.…”
Section: Discussionmentioning
confidence: 99%
“…14) UGT1A4 and UGT2B7 mRNAs are expressed at high levels among the hepatic UGT isoforms involved in E17G formation, whereas UGT1A10 has been found predominantly in the extrahepatic tissues. 2) In rats, E17G is formed by Ugt1a2, Ugt2b2, and Ugt2b3 15) and there is a tissue difference in the mRNA expression of these Ugt isoforms.…”
mentioning
confidence: 99%
“…Remarkable decreases in the functional expression of drug-metabolizing enzymes that mediate nonrenal drug clearance, particularly phase I oxidation by cytochrome P450 (P450) enzymes, have been well documented in the setting of kidney disease (Naud et al, 2012;Lalande et al, 2014;Yeung et al, 2014). Phase II conjugation via acetylation (Simard et al, 2008) is also decreased by kidney disease, but glucuronidation is not affected (Yu et al, 2006). However, the effect of CKD on other drug-metabolism pathways is less clear.…”
Section: Introductionmentioning
confidence: 99%