Melatonin and vitamin C administration ameliorate diazepam-induced oxidative stress and cell proliferation in the liver of rats.
OBJECTIVE
Oxidative stress is a likely molecular mechanism in long-term diazepam administration. The benefits of antioxidants (melatonin and vitamin C) against diazepam-induced cell proliferation, DNA synthesis and oxidative damage were investigated in this study.


METHODS
Four equal-sized groups of male rats [control, diazepam (3 mg/kg), diazepam plus melatonin (5 mg/kg) and diazepam plus vitamin C (50 mg/kg)] were used. Levels of lipid peroxides (LPO), superoxide dismutase (SOD) activity and glutathione (GSH) concentration were measured in tissue homogenates. Cell proliferation and rate of DNA synthesis were detected by autoradiography.


RESULTS
Results documented increased labelling index, (3)H-thymidine incorporation (DNA synthesis), LPO plus decrease in GSH levels and SOD activity in livers of diazepam-administered rats versus those of controls. When melatonin and vitamin C were given to diazepam-administered rats, they almost attenuated the increase of labelling index, DNA synthesis and LPO, and restored the levels of GSH and SOD activity.


CONCLUSIONS
These results suggest long-term hazard in use of drugs such as diazepam; they may be toxic and damage terminates in complex liver damage. Furthermore, melatonin and vitamin C may be useful in combating free radical-induced liver injury resulting from hazard and/or repeated diazepam administration.
El-Sokkary
G H
GH
Department of Zoology, Faculty of Science, Assiut University, Assiut, Egypt. Elsokkary2000@yahoo.com
D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D001345:Autoradiography; D002455:Cell Division / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D008054:Lipid Peroxides; D013482:Superoxide Dismutase; D005978:Glutathione; D008550:Melatonin; D001205:Ascorbic Acid; D003975:Diazepam