Background Acetaminophen (ACN) is a well-known analgesic commonly used to induce acute hepatic injury. Oxidative stress and inflammation are the main pathogenic mechanisms that contribute to ACN-induced hepatotoxicity. Vitamin D is reported to have a potential antioxidant and anti-inflammatory actions.
Aim of the work: The aim of the present study is to investigate the effects of pretreatment with vitamin D agonist paricalcitol in ACN induced hepatic dysfunction and to test its role in caspase-1 gene expression.
Materials and methods: This study was carried out on 40 male albino rats, divided equally into 4 groups. Control group received vehicle, Paricalcitol treated group (PC) received 200 ng intraperitoneally three times a week for 9 days, ACN-treated group received ACN (ACN)orally 2 g/kg body weight on day nine, and Paricalcitol-pretreated plus ACN pretreated group (PC+ACN), treated similar to PC and ACN groups.
Results: The PC treated normal rats did not show any significant differences from control group as regards to all the parameters measured or the histopathological changes. Histological examination showed disruption of the liver architecture in ACN group as compared to control animals. Furthermore, ACN group showed significant increase in all hepatic biomarkers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ glutamyl transferase (γGT), serum bilirubin, and a significant decrease in serum albumin. Similarly, the same group showed significant elevation of oxidative marker Malondialdehyde (MDA) and significant decrease of the antioxidant reduced glutathione (GSH) in both serum and hepatic tissue. In addition, the proinflammatory cytokines TNF-α IL-6 and IL-1β were significantly increased in both serum and hepatic tissue homogenate. Moreover, ACN-treated animals showed significant rise of mRNA of caspase-1 gene in their liver tissues. Pretreatment with paricalcitol prevented all the above parameters in the PC+ACN group. Paricalcitol pretreatment, also, down regulated the caspase-1 expression in the ACN-treated group but not in normal rats. Serum calcium and systolic blood pressure did not change significantly in all groups.
Conclusion: Vitamin D agonist paricalcitol has a protective effect against ACN-induced acute hepatic injury through antioxidant and anti-inflammatory actions. Moreover, it could down regulate caspase-1 gene expression in hepatic tissue with possible function as an anti-pyroptotic agent.