Acarbose alone or in combination with ethanol potentiates the hepatotoxicity of carbon tetrachloride and acetaminophen in rats

Wang, Peiyu; Kaneko, Takashi; Wang, Yuan; Sato, Akio

doi:10.1002/hep.510290109

Cited by 40 publications

(24 citation statements)

References 55 publications

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“…The activity of hepatic CYP2E1 was assessed by measuring the demethylation rate of dimethylnitrosamine (DMN) as described by Wang (1999). The DMN demethylation reaction mixture (1.0 ml) contained a final concentration of 0.07 mM EDTA, 0.2 mM NADP, 14 mM MgCl 2 , 215 mM KCl, 70 mM Tris-HCl buffer (pH 7.4), 10 mM isocitrate, 0.3 units of isocitrate dehydrogenase and 1.0 mM DMN in addition to the microsomes corresponding to 0.5 mg protein.…”

Section: Measurements Of Hepatic Cyp2e1 Protein and Activitymentioning

confidence: 99%

One-Day Dietary Restriction Changes Hepatic Metabolism and Potentiates the Hepatotoxicity of Carbon Tetrachloride and Chloroform in Rats

Qin

Wang

et al. 2007

Tohoku J. Exp. Med.

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Although dietary restriction (DR) is common in modern society, research about hepatic metabolism and the hepatotoxicity induced by DR has been conducted less intensively than that induced by fasting. In the present study, we fed male Wistar rats at five levels of food intake for one day, including conventional feeding (60 kcal), three of DR (45, 30, and 15 kcal), and fasting (0 kcal), and observed the metabolic changes of hepatic cytochrome P450 2E1(CYP2E1) and the hepatotoxicity of chloroform (CHCl 3 ) and carbon tetrachloride (CCl 4 ). The CYP2E1 content was significantly increased in 15 kcalfood and fasting groups. The hepatic glutathione (GSH) content, which protects the liver from hepatotoxic agents, was depleted in 15 kcal-food and fasting groups. After the challenge by CHCl 3 and CCl 4 , the activities of aspartate aminotransferase and alanine aminotransferase, marker enzymes for liver damage, were elevated remarkably at all food groups. Moreover, their activities increased significantly in DR groups, in comparison to the corresponding 60 kcal-food group. After the challenge, the hepatic GSH content was also depleted significantly in 15 kcal-food and fasting groups. CHCl 3 was cleared by hepatic metabolism about 8-10 times faster than that of CCl 4 . Similarly, the areas under the blood concentration-time curve of CCl 4 was as much as twice that of the corresponding CHCl 3 . In conclusion, when food was restricted to less than half of conventional amount, hepatic metabolism was affected and the hepatotoxicity induced by CCl 4 or CHCl 3 was augmented by, at least in part, CYP2E1 induction and GSH depletion. dietary restriction; hepatotoxicity; hepatic cytochrome P450 2E1; chloroform; carbon tetrachloride

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Section: Measurements Of Hepatic Cyp2e1 Protein and Activitymentioning

confidence: 99%

One-Day Dietary Restriction Changes Hepatic Metabolism and Potentiates the Hepatotoxicity of Carbon Tetrachloride and Chloroform in Rats

Qin

Wang

et al. 2007

Tohoku J. Exp. Med.

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“…This may be due, in part, to the hypoglycemic effect of green tea, specifically the effect of EGCG as an a-glucosidase inhibitor (IC 50 = 0.11-0.734 mg / mL) 37,38), because STZ + GT rats did not exhibit any weight gain and there was an improvement in their general condition, despite deceased HbAlc levels, compared with STZ rats 17) . Acarbose and voglibose are other a-glucosidase inhibitors that have been reported to increase AST and ALT levels in rats 39,40) . In the present study, the high concentration of 5 % green tea also induced hepatic inflammatory markers in STZ diabetic rats.…”

Section: Discussionmentioning

confidence: 99%

Effect of Green Tea on the mRNA Expression of Matrix Metalloproteinases in the Liver and Kidney of Diabetic Rats

Iwai

Kamiya

Tsujiyama

et al. 2008

The Showa University Journal of Medical Sciences

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: Matrix metalloproteinases (MMPs) contribute to cardiovascular disease and are associated with vascular lesions in diabetes mellitus. In the present in vivo study, we investigated whether oral administration of green tea changes the mRNA expression of MMPs in diabetic rats, because green tea catechins inhibit mRNA expression and activity of MMPs in vitro. Experimental diabetes was induced in rats by a single injection of 50 mg / kg streptozotocin (STZ) into the tail vein. Diabetic rats were fed either a green tea-free diet (STZ rats) or a diet containing 5 % green tea (STZ + GT rats) for 4 weeks. Control rats are non-diabetic rats not treated with green tea. The mRNA expression of MMP-2, MN'IP-9, tissue inhibitor of metalloproteinases (TIMP) -1, TIMP-2, and TIMP-3 in rat liver and kidney was determined by real-time polymerase chain reaction. In the liver, there were no significant differences in the mRNA expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 between STZ rats and STZ + GT rats. However, TIMP-3 mRNA expression in the liver was significantly increased in STZ + GT rats compared with control and STZ rats. In the kidney, MMP-9 mRNA expression in STZ rats was significantly decreased compared with that in control rats, whereas that in STZ + GT rats recovered to levels the same as in control rats. MMP-2, TIMP-1, TIMP-2 and TIMP-3 mRNA expression in the kidney were significantly increased in STZ + GT rats compared with STZ rats. Thus, 5 % green tea treatment of STZ diabetic rats improved changes in the mRNA expression of MMPs and TIMPs in kidney tissue more efficiently than in the liver. The results of the present study suggest that the imbalance in the mRNA expression of MMPs and TIMPs in STZ diabetic rats is improved by green tea treatment.

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“…18) In the present study two models of hepatic fibrosis induced by CCl 4 and TAA have been used. Exposure to both CCl 4 and TAA is reported to induce CYP 450 2E1 which is principally involved in the toxicokinetic mechanism of these fibrotic agents, 19) and remains localised in perivenous lobules and happens to be is a major source of ODFR. 20) Although liver is endowed with a unique capacity to regenerate thereby replenishing most of the protective systems, fibrotic tissue represent a situation where anti-oxidant capacity is insufficient to cope with the generation of pro-oxidants.…”

Section: Discussionmentioning

confidence: 99%

Reversal of Fibrogenic Events in Liver by Emblica officinalis (Fruit), an Indian Natural Drug

Abdullah

Mondhe

Gupta

et al. 2005

Biological & Pharmaceutical Bulletin

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A hydroalcoholic (50%) extract of Emblica officinalis (fruit) (EO-50) reduced the severity of hepatic fibrosis induced by carbon tetrachloride (CCl 4 ) and thioacetamide (TAA). Improved liver function was observed by measuring the levels of aspartate aminotransaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin in serum. Hepatic parameters monitored were the levels of glutathione (GSH), lipid peroxidation (LPO) and hydroxyproline and the activities of catalase, glutathione peroxidase (GPx), Na

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Acarbose alone or in combination with ethanol potentiates the hepatotoxicity of carbon tetrachloride and acetaminophen in rats

Cited by 40 publications

References 55 publications

One-Day Dietary Restriction Changes Hepatic Metabolism and Potentiates the Hepatotoxicity of Carbon Tetrachloride and Chloroform in Rats

One-Day Dietary Restriction Changes Hepatic Metabolism and Potentiates the Hepatotoxicity of Carbon Tetrachloride and Chloroform in Rats

Effect of Green Tea on the mRNA Expression of Matrix Metalloproteinases in the Liver and Kidney of Diabetic Rats

Reversal of Fibrogenic Events in Liver by Emblica officinalis (Fruit), an Indian Natural Drug

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