Hepatotoxicity and gene expression down-regulation of CYP isozymes caused by renal ischemia/reperfusion in the rat.
Renal ischemia/reperfusion (I/R) occurs in many clinical scenarios, including trauma, elective surgery, and transplantation. Events initiated by this process can lead to inflammation in the kidneys, culminating in local injury as well as distant organ dysfunction. The objectives of this study were to investigate the changes in the functions of the liver and the regulation of gene expression of cytochrome P450 (CYP) isozymes after renal I/R. Hepatoxocity was assessed by serum alanine aminotransferase (sALT), serum aspartate aminotransferase (sAST) and liver glutathione-S-transferase (GST) activities, liver glutathione (GSH) level, and histopathological examination. Hepatic cytochrome P4503A1 (CYP3A1) and cytochrome P4502E1 (CYP2E1) activities were measured by erythromycin N-demethylase (ERD) and aniline hydroxylase (ANH) activities, respectively. CYP3A1 and CYP2E1 mRNA expression was determined by RT-PCR. Results showed that activities of sALT and sAST were significantly increased, while hepatic CYP3A1and CYP2E1 activities as well as their respective mRNA levels were significantly decreased after renal I/R. Moreover, hepatic tissue congestion, degeneration, and local necrosis were observed in rats after 1, 4, and 8h renal reperfusion following 2h renal ischemia. In conclusion, the present study suggests that renal I/R can cause hepatotoxicity and gene expression down-regulation of CYP isozymes in rats.
Wang
Bao-Ying
BY
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China.
Li
Qi-Xiong
QX
Li
Jin
J
Xie
Xian-Fei
XF
Ao
Ying
Y
Ai
Yong-Xun
YX
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes; D007668:Kidney / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D009336:Necrosis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications* / Q000201:enzymology / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007527:Isoenzymes; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C465138:Cyp3a23-3a1 protein, rat; D051544:Cytochrome P-450 CYP3A