Involvement of Nitrergic and Opioidergic Systems in the Oxidative Stress Induced by BDL Rats

Aims: Liver cirrhosis is the irreversible end result of ‎fibrous scarring and associated with prominent morbidity and mortality. We aimed to investigate the involvement of nitrergic and opioidergic systems in the oxidative stress ‎induced by bile duct ligation (BDL) rats by evaluating the oxidative stress markers such as malondialdehyde (MDA), protein carbonyl content and total thiol in the plasma.

Methodology: Rats received injections of 3 mg/kg Nω-Nitro-L-arginine methyl-ester-hydrochloride (L-NAME: a NO-synthase inhibitor), 10 mg/kg opioid-receptors antagonist naltrexone (NTX), L-NAME (3 mg/kg)+NTX (10 mg/kg) or saline once daily for 28 days after BDL or sham surgery. Oxidative stress markers and biochemical indexes were measured in plasma samples.

Results: Results showed that serum levels of total bilirubin (TB) and alkaline phosphatase (ALP) to be significantly increased in BDL rats as compared with the Sham-operated (SO) group (P<0.05). MDA level was significantly increased and plasma total thiol content was insignificantly decreased in the BDL group as compared with relevant SO control. Treatment of NTX in BDL rats could significantly decrease the MDA production (P<0.05) as compared to BDL group. After 4 weeks of intervention, protein carbonyl content was significantly lower in BDL+L-NAME+NTX group as compared to the related SO and BDL groups (P<0.05).

Conclusion: The results of the study showed that nitrergic and opioidergic systems have various impacts in the oxidative stress induced by BDL rats. Blockage of opioid receptors in BDL rats during the study could significantly decrease the MDA production and protein carbonyl content as compared to BDL group, therefore, could moderately prevent the severe liver injury.