Melatonin protects the liver and erythrocytes against oxidative stress in cirrhotic rats.
BACKGROUND
Cirrhosis is a progressive chronic hepatopathy which constitutes an irreversible stage of liver dysfunction.


OBJECTIVE
To evaluate the oxidative stress in the blood of cirrhotic rats treated with the antioxidant melatonin.


METHODS
Cirrhosis was induced through inhalation of carbon tetrachloride. Liver integrity was evaluated by measuring serum enzymes, oxidative damage measured by lipoperoxidation, and antioxidant enzyme activity in erythrocytes. Lipoperoxidation, total nitrates, collagen, and histology by picrosirius staining were evaluated in the livers of these animals (n = 15), which were divided in three groups: control, carbon tetrachloride, and carbon tetrachloride + melatonin. Melatonin (20 mg/kg) was administered intraperitoneal from week 10 of carbon tetrachloride inhalation. In order to shorten the cirrhosis induction time, phenobarbital (0.3 g/L) was added to the animals' drinking water.


RESULTS
A significant impairment in the liver integrity of melatonin-treated animals as compared to cirrhotic animals was observed. In rat erythrocytes and liver, lipoperoxidation was significantly increased in the cirrhotic rats as compared to controls, as measured through thiobarbituric acid reactive substances, and significantly decreased in melatonin-treated animals as compared to cirrhotic ones. In blood, a decrease in superoxide dismutase and glutathione peroxidase enzymes was detected in the cirrhotic group as compared to the control group, with increased superoxide dismutase activity when melatonin was administered. A reduction in the levels of total nitrates was detected in the hepatic tissue of the animals in the carbon tetrachloride group as compared to the control group and an increase of these levels in the carbon tetrachloride + melatonin group. As for hepatic collagen, we found a significant increase in the carbon tetrachloride group as compared to the controls and a regression of these values in the treated group. In histology, the rats in the carbon tetrachloride group showed fibrosis and formation of fibrotic nodules, characterizing liver cirrhosis; there was reduction of nodules and fibrosis in the melatonin treated group.


CONCLUSIONS
The data allow us to suggest that the observed oxidative stress is related to the damages caused by carbon tetrachloride and that the use of melatonin can minimize these damages.
Lutheran University of Brazil, Canoas, RS, Brazil.
Darlan Pase da
DP
Rosa
Silvia
S
Bona
Douglas
D
Simonetto
Claudio
C
Zettler
Cláudio Augusto
CA
Marroni
Norma Possa
NP
Marroni
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology; D015227:Lipid Peroxidation / Q000187:drug effects; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000032:analysis* / Q000187:drug effects
D000975:Antioxidants; D002251:Carbon Tetrachloride; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D008550:Melatonin