Effect of resveratrol and melatonin on oxidative stress enzymes, regeneration, and hepatocyte ultrastructure in rats subjected to 70% partial hepatectomy.
OBJECTIVE
We sought to compare the antioxidant effects of resveratrol (R) and melatonin (M) after 70% partial hepatectomy (PH) as evidenced by ultrastructural alterations and effects on hepatocyte proliferation and apoptosis.


METHODS
Twenty-six male Wistar albino rats were randomized into four groups: group A (n = 8) resveratrol (R); group B (n = 8) melatonin (M); group C (n = 5) control PH; group D (n = 5) sham operated animals. The rats that received either R or M were sacrificed a week after PH. The malondialdehyde, glutathione, glutathione S-transferase, and nitric oxide levels were estimated in liver homogenates. The morphological changes were investigated using light and electron microscopy (EM). Cell proliferation was detected by immunohistochemical staining with monoclonal antibodies to Ki-67. Apoptosis was detected by the transferase-mediated dUTP nick end-labeling method.


RESULTS
PH induced hepatic LP, decreased GSH and NO, and inhibited GST activity (P < .05). R and M completely prevented PH-induced lipid peroxidation, decreased hepatic GSH and NO levels (P < .05). The inhibition of GST activity was prevented by R (P < .05), but not with M (P > .05). In the PH group EM showed severe morphological changes: mitochondrial degeneration, vacuoles, lipid droplets, and myelin-like figures. In both the R and M groups, morphological alterations repaired protective effects more prominently in the R group. Ki-67 indices (KI) were increased in the PH group and decreased in both R and M groups (P < .001). In the M group, KI was the lowest, but the difference compared with R was not significant (P > .05). Apoptosis was slightly increased in PH, but in either the R or M groups, apoptosis was intensively increased (P < .001). Increased apoptosis was greatest in the M group and the difference compared with the R group was statistically significant (P < .05).


CONCLUSIONS
R and M suppressed PH-induced oxidative damage, attenuated proliferation, and stimulated apoptosis. When we compared R and M, R showed more potent antioxidative effects and was morphologically more protective to hepatocytes. Antiproliferative effects of M were more potent. Because of their potent antioxidative effects, R and M can be effective for oxidative damage like ischemia-reperfusion injury; however, because of the adverse effects on proliferation and apoptosis more studies are needed in states in which regeneration is critical.
Kirimlioglu
H
H
Inonu University, Malatya, Turkey. vkirimlioglu@inonu.edu.tr
Ecevit
A
A
Yilmaz
S
S
Kirimlioglu
V
V
Karabulut
A Bay
AB
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000648:ultrastructure; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D008115:Liver Regeneration / Q000187:drug effects*; D008550:Melatonin / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D000975:Antioxidants; D013267:Stilbenes; D008550:Melatonin; D000077185:Resveratrol