The Protective Effects And Mechanisms Of Meloxicam On Liver Injury In A Rat Model Of Chronic Aluminium Exposure

Objective: To study the protective effects and mechanisms of meloxicam on liver injury in a rat model of chronic aluminium exposure.Methods: SD rats were intragastrically(ig)administered aluminum gluconate(200 mg Al3+·kg-1) once a day, five days a week, for 20 weeks. The COX2 inhibitor meloxicam(0.3 and 1.0 mg·kg-1)was ig administrated 30 min after aluminum gluconate treatment. HE staining was used to observe pathological changes in rat liver tissue. The biochemical method was adopted to detect ALT, AST and ALP levels in rat serum as well as SOD activity and MDA content in rat liver. The expression of COX2,EPs and PKA was measured by immunohistochemistry and western blotting. The contents of PGE2,c AMP,TNF-α,IL-1β and IL-6 were detected by the method of ELISA.Results: Our results showed an obvious vacuolar degeneration, granular degeneration and spotty necrosis in chronic aluminium(Al)-overload rat hepatocytes. The levels of ALT, AST and ALP were significantly increased in Al-treated rat serum. SOD activity was significantly decreased, and the contents of MDA,PGE2,c AMP,TNF-α,IL-1β and IL-6 was significantly increased in Al-treated rat liver. The expressions of COX2,EP1,EP 2,EP 4 and PKA protein in Al-treated rat liver were significantly increased, while EP3 protein expression was significantly decreased. Administration of meloxicam significantly alleviated liver function injury, blunted the decrease of SOD activity and the increase of MDA content,and increased significantly the expression of EP1,2,3,4. The content of PGE2, c AMP, TNF-α, IL-1β and IL-6 were significantly decreased in meloxicam-treated group compared with that of Al-treated group.Conclusion: Meloxicam has a significantly protective effect on liver injury caused by chronic aluminium exposure in rats. Reconstruction of PGE2-EPs-c AMP/PKA signaling pathways balance and further reducing inflammation and oxidative stress contributes to the protective mechanisms of meloxicam against liver injury.