Melatonin counteracts lipid peroxidation induced by carbon tetrachloride but does not restore glucose-6 phosphatase activity.
Carbon tetrachloride (CCl4) exerts its toxic effects by the generation of free radicals. In this study we investigated whether melatonin, a potent free radical scavenger, could prevent the deleterious effects of CCl4. Liver homogenates and liver microsomes were incubated with CCl4 in the presence of melatonin and lipid peroxidation and glucose-6 phosphatase (G6Pase) activity were determined. All doses of CCl4 (1, 0.5, 0.1 mM) produced significantly high levels of lipid peroxidation, as reflected by increased levels of malonaldehyde and 4-hydroxyalkenals, in both liver homogenates and liver microsomes. These doses of CCl4 concommitantly reduced the activity of microsomal G6Pase. Co-incubation with melatonin dose-dependently (2, 1, 0.5 mM) inhibited the production of lipid peroxidation, but it was unable to restore the activity of G6Pase. In in vivo studies, rats were also treated with melatonin (10 mg/kg, i.p.), given 30 min before and 60 min after the administration of CCl4 (5 ml/kg, i.p.). Significantly elevated levels of lipid peroxidation were measured in the liver and kidney. Melatonin prevented the CCl4-induced lipid peroxidation in the kidney, but not in the liver. These data suggest that melatonin may provide protection against some of the damaging effects of CCl4, possibly due to its ability to scavenge toxic free radicals.
Daniels
W M
WM
Department of Cellular and Structural Biology, University of Texas Health Sciences Center at San Antonio 78284-7762, USA.
Reiter
R J
RJ
Melchiorri
D
D
Sewerynek
E
E
Pablos
M I
MI
Ortiz
G G
GG
D000818:Animals; D002251:Carbon Tetrachloride / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D016166:Free Radical Scavengers; D008315:Malondialdehyde; D002251:Carbon Tetrachloride; D005952:Glucose-6-Phosphatase; D008550:Melatonin