Oxidative Damage of Biomolecules in Mouse Liver Induced by Morphine and Protected by Antioxidants

• Published in: Basic & clinical pharmacology & toxicology Vol. 95; no. 2; pp. 53 - 58
• Main Authors: Zhang, Yun‐Tao, Zheng, Qiu‐Sheng, Pan, Jing, Zheng, Rong‐Liang
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science, Ltd 01-08-2004; Blackwell
• Subjects: Alanine Transaminase - blood; Alanine Transaminase - drug effects; Animals; Antioxidants - administration & dosage; Antioxidants - pharmacokinetics; Antioxidants - therapeutic use; Ascorbic Acid - administration & dosage; Ascorbic Acid - pharmacokinetics; Ascorbic Acid - therapeutic use; Biological and medical sciences; Catalase - antagonists & inhibitors; Catalase - drug effects; Catalase - metabolism; Chemical and Drug Induced Liver Injury - diagnosis; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - prevention & control; China; Chromatography, High Pressure Liquid - methods; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - antagonists & inhibitors; Deoxyguanosine - chemistry; Deoxyguanosine - metabolism; DNA Damage - drug effects; DNA Damage - physiology; Drug Administration Schedule; Drug Therapy, Combination; Electrophoresis - methods; Glutathione - administration & dosage; Glutathione - pharmacokinetics; Glutathione Peroxidase - antagonists & inhibitors; Glutathione Peroxidase - drug effects; Glutathione Peroxidase - metabolism; Injections, Intraperitoneal; Liver - chemistry; Liver - drug effects; Liver - metabolism; Malondialdehyde - antagonists & inhibitors; Malondialdehyde - chemistry; Malondialdehyde - metabolism; Medical sciences; Mice; Morphine - administration & dosage; Morphine - adverse effects; Morphine - metabolism; Organic Chemicals - adverse effects; Organic Chemicals - antagonists & inhibitors; Organic Chemicals - chemistry; Oxidation-Reduction; Oxidative Stress; Pharmacology. Drug treatments; Phenylhydrazines; Proteins - metabolism; Superoxide Dismutase - antagonists & inhibitors; Superoxide Dismutase - drug effects; Superoxide Dismutase - metabolism; Digestive system; Liver; Rodentia; Opiates; Morphine; Narcotic analgesic; Antioxidant; Prevention; Vertebrata; Mammalia; Mouse; Animal; Lesion
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/j.1742-7843.2004.950202.x

: This study investigates the oxidative damage of biomolecules in livers of mice treated with morphine intraperitoneally. The oxidative damage of DNA as measured by single cell electrophoresis and high‐performance liquid chromatography equipped with electrochemical and UV detection, the protein carbonyl content was measured by 2,4‐dinitrophenylhydrazine method, and the malondialdehyde content was measured by the HPLC method. The activities of antioxidative enzymes, superoxide dismutase, catalase and glutathione peroxidase, and the activity of alanine aminotransferase were assayed by spectrophotometer method. Glutathione and oxidized glutathione were detected by fluorescence spectrophotometer method. All the indexes of oxidative damage, such as 8‐OHdG, protein carbonyl group and malondialdehyde content, and the activity of alanine aminotransferase (n=27) increased significantly compared to those of control (n=27) (P<0.01) in livers of morphine‐administered alone mice, while the indexes related with the in vivo antioxidative capacity, such as the ratio of glutathione and oxidized glutathione, activities of superoxide dismutase, catalase and glutathione peroxidase significantly decreased (P<0.01). When mice were treated with morphine combined with exogenous antioxidants, glutathione and ascorbic acid, all the indexes of oxidative damage and the activity of alanine aminotransferase showed no changes as compared to those of control (P>0.05), i.e., both glutathione and ascorbic acid completely abolished the damage of morphine on the hepatocyte. These results implied that morphine caused a seriously oxidative stress in mice livers and hence caused hepatotoxicity, while exogenous antioxidants were able to prevent the oxidative damage of biomolecules and hepatotoxicity caused by morphine. Thus, blocking oxidative damage may be a useful strategy for the development of a new therapy for opiate abuse.