Amelioration of immobilization stress-induced biochemical and behavioral alterations and mitochondrial dysfunction by naringin in mice: Possible mechanism of nitric oxide modulation

Objective: The present study was undertaken to evaluate the effects of naringin on immobilization stress-induced biochemical-behavioral changes and mitochondrial dysfunction in mice. Methods: Mice were randomized and grouped based on body weights. Respective drug treatments were given for 14 d, and on the 15th day all the animals were subjected to a 6-hour immobilization stress; then all the animals were subjected to various behavioral paradigms and were sacrificed. Various biochemical parameters and mitochondrial functions were analyzed using brain homogenate. Results: The 6-hour acute immobilization stress significantly altered the behavioral (anxiety and memory) and biochemical parameters coupled with mitochondrial dysfunction in mice. Fourteen days pretreatment with naringin (50 and 100 mg/kg, per oral) significantly inhibited the behavioral and biochemical alterations and mitochondrial dysfunction caused by acute immobilization stress (P<0.05). Further, pretreatment with L-arginine (50 mg/kg, intraperitoneally), a nitric oxide precursor, reversed the protective effect of naringin (P<0.05). In addition, pretreatment with N ^G-nitro-L-arginine methyl ester (5 mg/kg, intraperitoneally) caused potentiation in the protective effect of naringin. Conclusion; These results suggest the possible involvement of nitrergic pathway in the protective effect of naringin against immobilization stress-induced behavioral, biochemical and mitochondrial dysfunctions in mice.