ABSTRACT
Acute p.o. administration of 99.5% ethanol (0.1 ml) to fasted mice produced heart toxicity. Pretreatment with p.o. administration of tetramethylpyrazine (TMP) could prevent such toxicity effectively and dose-dependently. The maximal antioxidative effect against 99.5% ethanol-induced heart toxicity could be observed at 1 hour after TMP administration. In order to further investigate the heart protective mechanism of TMP, both lipid peroxidation level in vivo and superoxide scavenging activity were conducted. TMP exhibited a dose-dependently anti-lipid peroxidation effect in mice heart homogenate, and results indicated that 99.5% ethanol-induced intoxicated mice hearts have higher malonic dialdehyde (MDA) levels compared with those in TMP administrated mice hearts. These results suggest that the potentially heart protective mechanism of TMP could be contributed, at least in part, to its prominent anti-lipid peroxidation and anti-free radical formation effects, hence it could protect the heart from lipid peroxidation-induced heart toxicity.
Subject(s)
Antioxidants/pharmacology , Central Nervous System Depressants/adverse effects , Ethanol/adverse effects , Lipid Peroxidation/drug effects , Pyrazines/pharmacology , Animals , Dose-Response Relationship, Drug , Male , Malondialdehyde/metabolism , Mice , Mice, Inbred ICR , Myocardium/metabolismABSTRACT
The purpose of this study was to investigate the antioxidant effects of a hot water extract of Panax notoginseng (PNG) against chronic ethanol-induced hepatotoxicity. Fifty mice were divided into fi ve equal groups with 10 in each group. Group 1 (control) received saline, whereas group 2 received ethanol (70%, 0.1 mL, p.o.) once daily for 4 weeks, which induced hepatotoxicity, manifested biochemically by a significant elevation of serum enzyme activities, such as SGOT and SGPT. Hepatotoxicity was further evidenced by a significant increase in the hepatic lipid peroxidation measured. Groups 3-5 were administered a hot water extract of PNG at doses of 10, 25 and 50 mg/kg 2 weeks after initiating oral administration of ethanol, for a further 2 weeks. PNG ameliorated the rise in serum sGOT and sGPT induced by chronic ethanol administration. The mice were killed after PNG administration. In a separate study, PNG inhibited the lipid peroxidation in the mouse liver homogenate induced by ethanol in a dose-dependent manner. The findings indicate that PNG is an efficient cytoprotective agent against chronic ethanol-induced hepatotoxicity, possibly through inhibition of the production of oxygen-free radicals that cause lipid peroxidation.
Subject(s)
Antioxidants/pharmacology , Chemical and Drug Induced Liver Injury/prevention & control , Panax , Phytotherapy , Plant Extracts/pharmacology , Administration, Oral , Animals , Antioxidants/administration & dosage , Antioxidants/therapeutic use , Dose-Response Relationship, Drug , Ethanol , Inhibitory Concentration 50 , Liver/drug effects , Liver/enzymology , Liver/pathology , Liver Function Tests , Male , Mice , Mice, Inbred ICR , Plant Extracts/administration & dosage , Plant Extracts/therapeutic useABSTRACT
Angelica archangelica (AAA) has been effectively used in folk medicines as a remedy against stomachal and intestinal disturbances, arthritic disease, etc. However, there is still lack of scientific proof about its antioxidant capability. This study aimed at investigating the effects of total AAA against chronic ethanol-induced hepatotoxicity. ICR mice were divided into five groups, each consisting of 10 animals. A single dose of ethanol (70%, 0.1 ml, p.o.) was used to induce hepatotoxicity in these mice which resulted in a significant elevation of the activities of serum GOT and GPT. Treatment of mice with AAA (10, 25, and 50 mg/kg p.o.) after 2 weeks ameliorated the ethanol-induced hepatotoxicity effects. Hepatotoxicity was evidenced by a significant increase in hepatic lipid peroxidation manifested as the presence of malondialdehyde. It was found that AAA inhibits the malondialdehyde formation in mouse liver homogenates both in vitro and in vivo. AAA is cytoprotective agent effective against chronic ethanol-induced hepatotoxicity, possibly through inhibition of the production of oxygen free radicals that cause lipid peroxidation, and hence indirectly protects the liver from oxidative stress.
Subject(s)
Angelica archangelica , Hepatitis, Alcoholic/drug therapy , Phytotherapy , Plant Preparations/therapeutic use , Animals , Hepatitis, Alcoholic/metabolism , Lipid Peroxidation , Male , Malondialdehyde/metabolism , Mice , Mice, Inbred ICRABSTRACT
In this study, the intraperitoneal administration of 1 mg/kg thioacetamide (TAA) produced hepatotoxicity in mice. The increase in serum SGOT and SGPT produced at 24 h by this regimen was decreased in a dose-dependent manner by coadministration of tetramethylpyrazine (TMP; 10, 25 and 50 mg/kg). A rise in serum interleukin-2 was similarly prevented. Increased concentrations of malondialdehyde (MDA) generated in vitro in liver homogenates prepared from TAA-treated mice were decreased by TMP treatments. The increase in MDA produced by TAA was also prevented by in vitro addition of TMP to liver homogenates. These results suggest that part of the hepatocellular injury induced by TAA is mediated by oxidative stress caused by the action of cytokines through lipid peroxidation. TMP appears to act by preventing lipid peroxidation.
