الفهرس 
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Abstract
Biochemical and molecular effects of melatonin on liver injury in rats
Liver injury often develops to fibrosis then to irreversible cirrhosis that may be progressively complicated with liver cancer; a common link between chronic liver damage and hepatic fibrosis may be related to oxidative stress, pro inflammatory cytokines and newly altered cells formation.
Recent studies showed that melatonin exerts its cytoprotective effects in various experimental models of acute liver injury and reduces fibroblast proliferation and collagen synthesis, indicating that melatonin may have therapeutic effects on acute and chronic liver injury, through its antioxidant and anti-inflammatory action.
This study carried out on a total of 60 male albino rats fed on a commercial diet and water, classified into four groups each group contained 15 rats and let for 2 weeks for acclimation before starting the experiment.
group I (control group):
The rats were kept on normal basal diet and water ad libitum and were given of 0.9% NaCl solution (1ml/ rat) given by intraperitoneal injection once daily for 8 weeks.
group II (Melatonin treated group):
The rats were treated with melatonin dissolved in 0.9% NaCl solution that given by intraperitoneal injection in a dose of 5 mg/kg body weight once daily for 8 weeks
group III (TAA treated group):
The rats were received intraperitoneal injection of TAA dissolved in 0.9 NaCl solution a dose of 150 mg/kg body weight three times a week for 8 weeks for induction of liver injury.
group IV (TAA and Melatonin treated group):
The rats received simultaneously intraperitoneal injection of TAA in a dose of 150 mg/kg body weight three times a week together with melatonin in a dose of 5 mg/kg body weight given by intraperitoneal injection once daily for 8 weeks ( melatonin treatment started one week before TAA treatment).
Results of the present study revealed the following:
1. A significant decrease in body weight and increase in liver weight and liver weight index in TAA treated group as compared to control group, while in melatonin treated TAA intoxicated group, there were a significant increase in body weight and decrease liver weight index as compared to TAA treated group but failed to return its levels to control.
2. A significant increase in serum activities of ALT, AST, ALP and LDH in TAA treated group as compared to control group, while in melatonin treated groups there were a significant decrease in serum activities of ALT, AST, ALP and LDH as compared to TAA treated group.
3. A significant decrease in serum total protein and albumin concentration in TAA treated group as compared to control group, while in melatonin treated groups there were a significant increase in serum total protein and albumin as compared to TAA treated group. However, melatonin unable to return serum total protein and albumin concentration as compared to control group when treated to the liver intoxicated rats.
4. A significant increase in plasma ammonia and serum total bilirubin concentration in TAA treated group as compared to control group, while in melatonin treated groups there were a significant decrease in plasma ammonia concentration and serum total bilirubin as compared to TAA treated group.
5. A significant increase in triacylglycerol and vLDL-c and LDL-c with significant decrease in HDL-c concentration in TAA treated group as compared to control group, while in melatonin treated groups there were a significant decrease in serum triacylglycerol, vLDL-c, LDL-c, and significant increase in HDL-c concentration.
6. A significant increase in MDA, decrease in TAC and GSH concentration in TAA treated group as compared to control group confirming the hepatic injury due to oxidative stress occurred in this group. Compared to TAA group, Co-administration of melatonin alleviated the altered liver oxidative/ antioxidative indices, which was evidenced by significant decrease in MDA and increase in TAC and GSH which indicate the antioxidant effect of melatonin.
7. A significant increase in TNF-α, IL-1β, fibronectin gene expression in TAA treated group as compared to control group confirming the hepatic injury in this group. Compared to TAA group, Co-administration of melatonin alleviated the increasing of pro-inflammatory cytokines gene expression, which was evidenced by significant decrease in TNF-α, IL-1β and fibronectin but not return to its normal level.
8. Histopathological examination revealed that the liver of control and melatonin treated group showed normal histological appearance of hepatocyte and blood vessels. The microscopical finding of TAA treated group exhibited marked diffuse hepatic vacuolation, marked periportal fibrosis, oval cell hyperplasia periportal fibrosis, giving features of interlobular and intralobular cirrhosis associated with marked hepatic regeneration and severe degree of hepatic vacuolation, while the treatment by melatonin with TAA improve the histopathological appearance of hepatocyte and protect it from damaging induced by TAA which noticed histological by mild hepatic vacuolation.