Effects of Co-enzyme Q10 on Brain and Liver Proliferating Cell Nuclear Antigen (PCNA) in Methionine and Choline Deficient (MCD) Diet-induced Non-Alcoholic Steatohepatitis (NASH) in Albino Rats

The present study aimed to evaluate the hepato-protective and neuro-protective activity of Co-enzyme Q (CoQ10) on non-alcoholic steatohepatitis (NASH) in albino rats induced by methionine and choline deficient (MCD) diet. To acheive this aim, thirty Wistar rats were fed MCD diet for 8 weeks to induce non-alcoholic steatohepatitis. CoQ (10 mg/kg/day) were orally administrated of was done for the two consecutive weeks. Twenty-four hours after the last dose of the drug behavioural test, namely activity cage test was performed and the activity counts were recorded. Serum alanine transaminase, aspartate aminotransferase, gamma-glutamyl transferase, total/direct bilirubin, alkaline phosphatase and albumin were valued to assess liver function. Moreover, hepatic cytokines interleukin-6 (IL-6) as well as its modulator nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were determined. In addition, brain biomarkers viz. ammonia, nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) were measured which are reliable indices to assess brain injury. Histopathological and immunohistochemical examination of proliferating cell nuclear antigen (PCNA) in brain and liver tissues were also evaluated. Results of the present study showed that induction of NASH with MCD diet was associated with hyperlocomotor activity as well as a increase in the brain ammonia and NO contents and decrease in the brain BDNF level as compared to the normal rats at P<0.05. Moreover, MCD-induced NASH showed impairment in the liver functions with an increase in the liver inflammatory markers. Oral treatment of MCD diet fed rats with CoQ10 for 14 days showed a significant decrease in the hyperlocomotor activity and in the brain content of ammonia and NO as well as a significant increase in BDNF at P<0.05. CoQ10 also showed a marked improvement in serum liver biomarkers. Furthermore; histopathological and immunohistochemical examination of PCNA showed a marked improvement in both tissues; brain and liver isolated from CoQ10 treated group. From all the previous results, we can conclude that CoQ10 has a hepato-protective and neuro-protective role in modulation of enzymatic biomarkers, inflammatory cytokines and cell proliferative mechanisms in MCD diet-induced NASH in rats due to its antioxidant and anti-inflammatory effects.