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Prevention by melatonin of hepatocarcinogenesis in rats injected with N ‐nitrosodiethylamine
Author(s) -
Subramanian Perumal,
Mirunalini Shankaran,
Dakshayani Kadiyala Babu,
PandiPerumal Seithikurippu R.,
Trakht Ilya,
Cardinali Daniel P.
Publication year - 2007
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2007.00478.x
Subject(s) - tbars , glutathione peroxidase , melatonin , endocrinology , aspartate transaminase , medicine , glutathione , alanine transaminase , liver function , superoxide dismutase , chemistry , lipid peroxidation , antioxidant , biology , biochemistry , enzyme , alkaline phosphatase
N ‐nitrosodiethylamine (NDEA) is a potent carcinogenic agent that induces liver cancer. To evaluate the chemopreventive function of melatonin in this experimental model, Wistar male rats received a single i.p. injection of NDEA or vehicle followed by weekly s.c. injections of carbon tetrachloride or vehicle for 6 weeks. Melatonin (5 mg/kg body weight) or its vehicle (0.5 mL saline) was given i.p. on a daily basis 2 hr before lights off for 20 wk. At the end of this period the rats were killed and liver and blood samples were taken for histological and biochemical studies. As markers for liver function, the activity of aspartate transaminase (AST) and alanine transaminase (ALT) and the levels of α‐fetoprotein were measured in serum. To assess lipid peroxidation and the antioxidant status in liver and blood, the levels of thiobarbituric acid reactive substances (TBARS) and of reduced glutathione (GSH) were measured. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S‐transferase (GST) was assessed in liver and erythrocyte fraction of NDEA‐treated rats. NDEA administration inhibited body weight, macro‐ and microscopically detectable liver tumors and increased levels of plasma AST, ALT and α‐fetoprotein. NDEA treatment decreased liver TBARS levels and CAT and SOD activities and increased liver GSH levels and GST and GPx activities. Plasma TBARS were augmented, while plasma GSH levels and the activities of erythrocyte CAT, SOD, GST and GPx decreased, in NDEA‐treated rats. Melatonin administration significantly curtailed tumor development and counteracted all the biochemical effects.