Abstract
Context: Celecoxib (Cele), a nonsteroidal anti-inflammatory drug (NSAID) is linked with a spectrum of hepatotoxic influences, however the underlying mechanism (s) by which this drug induces liver damage is still unexplored. Aims: To demonstrate the hepatotoxic mechanism (s) of Cele in rats and the prophylactic roles of melatonin (Mel) and/or quercetin (Qr). Methods: Rats were divided into eight groups, GI, served as control group; GII, Mel (12 mg/kg/day) treated group; GIII, Qr (10 mg/kg/day) treated group; GIV, Mel and Qr treated group; GV, Cele (50 mg/kg/day) treated group; GVI, Cele treated group concurrently with Mel GVII, Cele treated group concurrently with Qr; GVIII, Cele treated group concurrently with the combination of the two agents. The efficiency of Mel and/or Qr on hepatic histomorphology was also investigated. Results: Cele significantly reduced hepatic succinate dehydrogenase and adenosine triphosphate and increased adenosine diphosphate versus the control group. Cele also caused rising in hepatic malondialdehyde, nitric oxide, tumor necrosis factor-a, transforming growth factor-n, caspase-3 and hydroxyproline as well as DNA damage along with depletion in catalase and glutathione reductase. Alteration in serum liver function markers and its histologic architecture were also observed in Cele treated group. Co-treatment of Cele treated rats with Mel and/or Qr, effectively ameliorated the deteriorations in the studied parameters as well as the histomorphologic liver pictures. Conclusions: Mel and/or Qr could protect the liver from Cele, toxicity, which was more pronounced in rats treated with the combination of the two agents.