Protective effects of glycine against diclofenac-induced toxicity in isolated rat hepatocytes.

Abstract

Diclofenac (DIC) is a common cyclo-oxygenase inhibitor that has been linked to liver toxicity. Alternatively, glycine (GLY) has several beneficial actions, including direct cytoprotective, anti-inflammatory, anti-apoptotic, and antioxidant effects. Hence, this study investigated the ability of GLY to protect isolated rat hepatocytes against DIC-induced injury. Hepatocytes were isolated using a modified collagenase-based rat liver perfusion and digestion method. Assessment was conducted on trypan blue (TB) uptake, as well as, reduced glutathione (GSH), lipid peroxidation (LPO), nitric oxide (NO), nuclear factor kappa B (NF-κB), and tumor necrosis factor-alpha (TNF-α) levels. Caspase-3 activity was also measured. Pre-incubation of hepatocytes with GLY (40 mM) for 30 minutes prior to treatment with DIC (200 µM) significantly mitigated hepatocytotoxicity. Additionally, the DIC-depleted GSH level was restored following GLY pretreatment. Moreover, levels of LPO, NO, NF-κB, TNF-α, and caspase-3 activity were normalized and diminished relative to the DIC-intoxicated group. Therefore, GLY prevented DIC-induced hepatocyte toxicity, at least partly, by its cytoprotective, antioxidative, anti-inflammatory, and anti-apoptotic properties. Further research regarding the clinical pharmacologic and toxicologic effects of administering GLY to patients treated with high-dose DIC is thus recommended.