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

Abstract

The present study was undertaken to evaluate the effects of naringin on immobilization stress-induced biochemical-behavioral changes and mitochondrial dysfunction in mice. 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. 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 NG-nitro-L-arginine methyl ester (5 mg/kg, intraperitoneally) caused potentiation in the protective effect of naringin. 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.