2-Nitropropane-induced lipid peroxidation: antitoxic effects of melatonin

The degree of lipid peroxidation (LPO) as indicated by the levels of thiobarbituric acid reactive substances, malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA), and the activity of sorbitol dehydrogenase (SDH) in serum as parameters of hepatotoxicity were studied in rats treated with a single intraperitoneal (i.p.) injection of the hepatocarcinogen 2-nitropropane (2-NP). Since melatonin, the main secretory product of the pineal gland, has been shown to protect against a number of toxic agents, it was given 30 min before 2-NP to test its protective effect against 2-NP toxicity. Significant increases in LPO in liver (P<0.0001), lung (P<0.05) and kidney (P<0.0001) were observed 24 h after 4 mmol/kg 2-NP while serum SDH activity was increased 470-fold. All parameters showed time (0, 4, 8, 24 h) and dose (0, 1, 2, 3, 4 mmol/kg) dependency. The induction of LPO by 2-NP was significantly reduced in lung and kidney when melatonin (2.5, 5 or 10 mg/kg) was given prior to 2-NP administration. The elevation in serum SDH caused by 2-NP was also reduced when melatonin was given. These findings show that 2-NP induces LPO and that pharmacological levels of melatonin can reduce the toxicity of this hepatocarcinogen.