Possible Protective Role of L-carnitine on Diclofenac Induced Hepatotoxicity in Adult Male Albino Rats (Histological, Immunohistochemical and Biochemical Study)

Introduction: Diclofenac (DCLF) is in common use worldwide as non steroidal anti-inflamatory drugs (NSAIDs) that have been reported to cause significant adverse effects. L-Carnitine has been proposed as antioxidant because it helps reduce oxidative stress. Aim of the Work: This work aimed to study the possible histological, immunohistochemical and biochemical changes of liver associated with diclofenac administration and to assess possible beneficial role L- carnitine (LC) on diclofenac (DCLF) induced hepatotoxicity. Materials and Methods: Fifty adult male albino rats were divided into 4 main groups. Group I: Served as positive and negative controls. Group II: Received LC in a dose of 50 mg/ kg intramuscular (IM) in 1 ml saline. DCLF treated group (III): Received DCLF 50 mg/ kg IM in 1 ml saline. Combined group (IV): Rats received LC then DCLF after 2 hours IM. The treatments were given for the rats 6 days/ week for two weeks. At the time of sacrifice, the rats were anaesthetized; blood samples were taken for measuring liver function tests. Specimens from the liver of each rat were taken for light and electron microscopic examination. Results: Histological examination of the liver of the rats of DCLF treated group revealed different degrees of focal lobular affection. Enlarged portal areas, congested portal and central veins, bile duct proliferation, cellular infiltration and fibrosis were detected. Significant decrease in area % of brown positive immunoreactions for glutathione peroxidase I (GPXI) was detected in comparison with control group. Necrosis of most of hepatocytes especially in those close to portal area was detected. Most of hepatocytes mitochondria appeared with ruptured membrane. Pretreatment with LC in combined group showed slight histological changes with sinusoidal congestion, minimal fibrosis around prominent portal area with significant increase in area % of GPX1 in comparison with DCLF treated group. Most of mitochondria appeared with intact membrane. There were significant elevations in liver function tests in DCLF treated group when compared with other groups with partial recovery in combined group. Conclusion: Results obtained in this study demonstrated that high doses of DCLF induced histological and biochemical changes in the liver due to oxidative stress and that the use of LC had partially reduced the DCLF induced toxicity. This may suggest that LC enhanced antioxidant defence and may be used as a cell protector for DCLF induced hepatotoxicity