Oxidative damage of biomolecules in mouse liver induced by morphine and protected by antioxidants.
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.
Zhang
Yun-Tao
YT
Institute of Biophysics, School of Life Sciences, Lanzhou University, Lanzhou, 730000, People's Republic of China.
Zheng
Qiu-Sheng
QS
Pan
Jing
J
Zheng
Rong-Liang
RL
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D002374:Catalase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D002681:China; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004586:Electrophoresis / Q000379:methods; D005978:Glutathione / Q000008:administration & dosage / Q000493:pharmacokinetics; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008099:Liver / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D008315:Malondialdehyde / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D009930:Organic Chemicals / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000737:chemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010659:Phenylhydrazines; D011506:Proteins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D009930:Organic Chemicals; D010659:Phenylhydrazines; D011506:Proteins; C004787:2,4-dinitrophenylhydrazine; D008315:Malondialdehyde; D009020:Morphine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000410:Alanine Transaminase; D003849:Deoxyguanosine; D005978:Glutathione; D001205:Ascorbic Acid