|Voglibose potentiates the hepatotoxicity of carbon tetrachloride and acetaminophen by inducing CYP2E1 in rats|
|Qin, LQ; Wang, PY; Wang, Y; Kaneko, T; Hoshi, K; Sato, A|
|关键词||voglibose hepatotoxicity carbon tetrachloride (CCl4) acetaminophen (APAP) cytochrome P450 2E1 (CYP2E1)|
|WOS标题词||Science & Technology|
|类目[WOS]||Gastroenterology & Hepatology|
|研究领域[WOS]||Gastroenterology & Hepatology|
|关键词[WOS]||ALPHA-GLUCOSIDASE INHIBITOR ; METABOLITE FORMATION ; LIVER-INJURY ; TOXICITY ; CYP3A ; CYTOCHROME-P-450 ; MICROSOMES ; MECHANISM ; ACARBOSE ; DAMAGE|
Background: Voglibose, is an a-glucosidase inhibitor used to decrease postprandial hyperglycemia in diabetic patients. Although clinical concern has not yet been raised, hepatic dysfunction has been reported in a few patients taking this drug,
Method: In the present study, we studied the effects of voglibose on the hepatotoxicity of carbon tetrachloride (CCl4) and acetaminophen (APAP) in rats, since both of these agents exert their effects through isoforms of cytochrome P450. Male Sprague-Dawley rats were given a daily ration (20 g) of powdered chow diet containing 0, 2.5, 5.0 or 10.0 mg/100 g of voglibose. Three weeks later, the rats were challenged with either 0.50 g/kg CCl4 orally or 0.75 g/kg APAP intraperitoneally for biochemical examinations or killed for an in vivo metabolism study.
Results: Voglibose at these three experimental doses potentiated CCl4 and APAP hepatotoxicity, as evidenced by significantly increased levels of both plasma asparate transaminase (AST) and alanine transaminae (ALT). The glutathione (GSH) content was decreased while malondialdehyde (MDA) increased in the liver after CCl4 or APAP administration. Hepatic cytochrome P450 2E1 (CYP2E1) concentration was increased at doses of 5.0 and 10.0 mg/100g of voglibose and its activity increased in the three voglibose dosage groups, while hepatic cytochrome P4503A (CYP3A) and cytochrome P450 1A2 (CYP1A2) were only slightly changed at any dose.
Conclusion: Our study demonstrated that voglibose can potentiate CC14 and APAP hepatotoxicity in rats by inducing hepatic CYP2E1. (c) 2005 Elsevier B.V. All rights reserved.
|作者单位||1.Peking Univ, Sch Publ Hlth, Dept Social Med & Hlth Educ, Beijing 100083, Peoples R China|
2.Univ Yamanashi, Sch Med, Dept Obstet & Gynecol, Tamaho, Yamanashi 4093898, Japan
3.Hebei Med Univ, Affiliated Hosp 4, Shijiazhuang 050011, Hebei Province, Peoples R China
4.Univ Yamanashi, Sch Med, Dept Environm Hlth, Tamaho, Yamanashi 4093898, Japan
|Qin, LQ,Wang, PY,Wang, Y,et al. Voglibose potentiates the hepatotoxicity of carbon tetrachloride and acetaminophen by inducing CYP2E1 in rats[J]. HEPATOLOGY RESEARCH,2005,33(1):50-56.|
|APA||Qin, LQ,Wang, PY,Wang, Y,Kaneko, T,Hoshi, K,&Sato, A.(2005).Voglibose potentiates the hepatotoxicity of carbon tetrachloride and acetaminophen by inducing CYP2E1 in rats.HEPATOLOGY RESEARCH,33(1),50-56.|
|MLA||Qin, LQ,et al."Voglibose potentiates the hepatotoxicity of carbon tetrachloride and acetaminophen by inducing CYP2E1 in rats".HEPATOLOGY RESEARCH 33.1(2005):50-56.|