| Project/Area Number |
10670344
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Public health/Health science
|
|---|
| Research Institution | Yamanashi Medical University |
|---|
Principal Investigator |
WANG Peiyu Yamanashi Medical University, Department of Environment Health, Research associate, 医学部, 助手 (10283201)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KANEKO Takashi Yamanashi Medical University, Department of Environment Health, Associate professor, 医学部, 助教授 (10233876)
SATO Akio Yamanashi Medical University, Department of Environment Health, Professor, 医学部, 教授 (40020747)
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
|---|
| Keywords | α-glucosidase inhibitor / acarbose / voglibose / CPY / hepatotoxicity / acetaminophen / carbon tetrachloride / diabetes / diabetes / Acarbose / CYP2E1 / Hepatotoxicity / Carbon Tetrachlorid / Acetaminophen |
|---|
| Research Abstract |
We studied the effects of α-glucosidase inhibitors (acarbose and voglivose) on cytochrome P450 (CYP) and hepatotoxicity Of carbon tetrachloride (CClィイD24ィエD2) and acetaminophen (AP) in rats, both of which exert their toxic effects through bioactivation associated with CYP2E1. We began the study with acarbose. Male Sprague-Dawley rots were kept on a daily ration (20 g) of powdered chow diet containing 0, 20, 40 or 80 mg/100 g of acarbose, with drinking water containing 0 or 10% of ethanol (v/v). Three weeks later, the rats were either killed for an in vitro metabolism study or challenged with 0.50 g/kg CCl ィイD24ィエD2 po or 0.75 g/kg AP ip. The ethanol increased the hepatic microsomal CYP2E1 level and the rate of dimethylnitosamine (DMN) demethylation. The 40 or 80 mg/100 g acarbose diet, which alone increased the CYP2E1 level and the rate of DMN demethylation, augmented the enzyme induction by ethanol. The 40 or 80 mg/100 g acarbose diet alone potentiated CClィイD24ィエD2 and AP hepatotoxicity, as evidenced by significantly increased levels of both ALT and AST in the plasma of rots pretreated with acarbose. Ethanol alone also potentiated the toxicity of both chemicals. When the 40 or 80 mg/100 g acarbose diet was combined with ethanol, the ethanol-induced potential/on of CCィイD24ィエD2 and AP hepatotoxicity was augmented. We performed the similar experiment on voglivose and found it (5.0 or 10.0 mg/100 g diet, 3 weeks) induced CYP2E1 and increased hepatotoxicity of CCィイD24ィエD2 (0.50 g/kg). Our study demonstrated that high doses of α-glucosidase inhibitors can potentiate CClィイD24ィエD2 and AP hepatotoxicity in rats by inducing hepatic CYP2E1.
|
