ABSTRACT
Stroke is the third leading cause of death and disability around the globe. The aim of the present investigation was to evaluate the protective effect of hesperidin and its nitric oxide mechanism against cerebral ischemia reperfusion injury. Bilateral common carotid artery occlusion for 30 min followed by 24 h reperfusion was given to induce ischemia in rats. Animals were pretreated with hesperidin (50 and 100 mg/kg, po) for 7 days. Various behavioural tests, oxidative stress parameters, endogenous antioxidant system, antioxidant enzyme activity and mitochondrial enzyme complex (I, II, III and IV) dysfunctions in cortex and striatum were assessed subsequently. Hesperidin (50 and 100 mg/kg) significantly improved neurobehavioral alterations (neurological score, locomotor activity, resistance to lateral push and hanging wire latency), attenuated oxidative damage, restored antioxidant and mitochondrial complex enzyme activities in cortex and in striatum regions of the brain as compared to their respective controls. L-arginine (100 mg/kg) or L-NAME (10 mg/kg) pretreatment with lower dose of hesperidin (50 mg/kg) significantly reversed or potentiated its protective effect, respectively which was significant as compared to hesperidin (50 mg/kg). The results highlight the involvement of nitric oxide mechanism in the protective effect of hesperidin against ischemia reperfusion injury induced alterations.
ABSTRACT
Stress is an aversive stimulus which disturbs physiological homeostasis and is reflected on a variety of biological systems. The present study was designed to investigate the nitric oxide mechanism in neuroprotective effect of trazodone and citalopram against acute immobilization-induced behavioral and biochemical alteration in mice. Mice were immobilized for a 6 h. Acute immobilization stress caused anxiety, hyperalgesia, impaired locomotor activity and oxidative damage. Pre-treatment with trazodone and citalopram significantly reversed immobilized stress-induced behavioral and biochemical alterations. L-arginine, pretreatment with trazodone or citalopram significantly reversed their protective effects. However, L-NAME or methylene blue pretreatment with trazodone or citalopram significantly potentiated their protective effects alone. Results suggest the involvement of nitric oxide pathways in the protective effect of trazodone and citalopram against immobilization stress induced behavioral and biochemical alterations.
ABSTRACT
Sibutramine is one of the very few drugs that are approved for long-term treatment of obesity. Sibutramine is a racemic mixture (RS) containing two equal forms of the R(+) and S(-) enantiomers. In this paper, we have investigated comparative anorexic effect of sibutramine enantiomers and their recemate form in rats. After obtaining two days of baseline results, rats were administered orally either with (RS)-sibutramine or its enantiomers (R)- or (S)-sibutramine at dose levels of 5, 10, 20 mg/kg each for 4 days and body weight, food intake and water intake were measured daily. Locomotor activity score of each rat was also recorded on each day. R-Sibutramine and (RS)-sibutramine produced dose dependant decrease in the body weight and food intake. On the other hand, (S)-sibutramine was shown to increase in these parameters. Neither sibutramine nor it's enantiomers showed any consistent effects on spontaneous motor activity (SMA) scores. In conclusion, (R)-sibutramine is better anorexic than or (RS)-sibutramine or it's (S)-enantiomers.