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.
Kim
S J
SJ
Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio 78284-7762, USA.
Reiter
R J
RJ
Rouvier Garay
M V
MV
Qi
W
W
El-Sokkary
G H
GH
Tan
D X
DX
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects*; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D009595:Nitroparaffins / Q000633:toxicity*; D011407:Propane / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000633:toxicity*
D000447:Aldehydes; D016166:Free Radical Scavengers; D008054:Lipid Peroxides; D009595:Nitroparaffins; D012997:Solvents; D008315:Malondialdehyde; D007064:L-Iditol 2-Dehydrogenase; C016617:2-nitropropane; D008550:Melatonin; C027576:4-hydroxy-2-nonenal; D011407:Propane