Sildenafil enhances the peripheral antinociceptive effect of ellagic acid in the rat formalin test.

OBJECTIVE: Ellagic acid (EA), a major polyphenolic compound of pomegranate juice, produces antinociceptive effects, which are mediated through opioidergic and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathways. The present study was conducted to elucidate the peripheral antinociceptive effect of EA alone and in combination with sildenafil in the rat formalin test. MATERIALS AND METHODS: Pain was produced by intraplantar injection of formalin (2.5%) in rats and nociceptive behavior was measured as the number of flinches every 5 min in 60 min after injection. RESULTS: Local administration of EA and sildenafil dose-dependently increased the nociception threshold in both phases of the test. Moreover, sub-effective doses of sildenafil (25 or 50 mcg/paw, i.p.) significantly and dose-dependently enhanced the antinociception induced by a sub-effective dose of EA (60 mcg/paw, i.pl.) in both phases of the test. The antinociception produced by these drugs alone, or in combination, was due to a peripheral site of action, since the administration in the contralateral paw was ineffective. CONCLUSION: Our results suggest that EA has local peripheral antinociceptive activity, and enhancement of this effect with sildenafil probably occurs through the inhibition of cGMP metabolism.

Protective effects of crocin on hemodynamic parameters and infarct size in comparison with vitamin E after ischemia reperfusion in isolated rat hearts.

Although reperfusion is a useful method for the survival of ischemic heart, harmful effects have been observed. This study was carried out to investigate the preconditioning and cardioprotective potential effects of crocin and vitamin E on the hemodynamic and infarct size in the ischemia-reperfusion model of isolated rat hearts. Animals were divided into a control group, an ischemia-reperfusion control group and three treatment groups: crocin (10, 20, and 40 mg/kg), vitamin E (100 mg/kg), and combination (crocin 40 mg/kg with vitamin E 100 mg/kg). The hearts were excised, quickly transferred to a Langendorff apparatus, and subjected to 30 min of global ischemia followed by 60 min of reperfusion. Left ventricular developed pressure, coronary perfusion pressure, left ventricular systolic pressure, myocardial contractility, rate pressure product, coronary flow, and infarct size were assessed. The successful induction of ischemia was determined by ST elevation on the electrocardiogram.The results showed that crocin significantly improved cardiac dysfunction and also reduced infarct size in the rat hearts. However, the combination of crocin 40 mg/kg and vitamin E 100 mg/kg had an even more significantly improved effect on the hemodynamic parameters and infarct size.Therefore, it can be suggested that the protective role of crocin may be due to the stability or reinforcement of antioxidant systems, and crocin could be useful for the treatment or prevention of cardiac dysfunction.

Neuroprotective effects of oral gallic acid against oxidative stress induced by 6-hydroxydopamine in rats.

Free radical-induced neural damage is implicated in neurodegenerative diseases and antioxidants have protective activity. In the present study, we examined the effect of gallic acid (GA; 50, 100 and 200mg/kg, p.o. for 10 days) on memory deficit and cerebral oxidative stress induced by 6-hydroxydopamine (6-OHDA; 8 µg/2 µL) injected into the medial forebrain bundle (MFB, full nigral lesion) as an animal model of Parkinson's disease (PD). The results showed that 6-OHDA significantly reduced the passive avoidance memory performance, non-enzymatic (total thiol) and enzymatic [glutathione peroxidase (GPx)] antioxidant contents and increased the level of malondialdehyde (MDA) in the hippocampus and striatum of vehicle-treated group as compared to sham-operated rats. Furthermore, oral administration of GA significantly increased the passive avoidance memory, total thiol and GPx contents and also decreased MDA levels in the above tissues. The results suggest that GA has neuroprotective activity against 6-OHDA-induced oxidative stress via enhancement of cerebral antioxidant defence.

Protective effects of crocin against cisplatin-induced acute renal failure and oxidative stress in rats.

BACKGROUND: The major side effect of cisplatin, used in some tumours, is nephrotoxicity. Reactive oxygen species and oxidative damage are the most important factors in cisplatin-induced acute renal failure. The main purpose of this study is to investigate the protective effects of crocin against cisplatin-induced acute renal failure and oxidative stress in rat. METHODS: In this study, animals were randomly divided into 5 groups (6 each). Group one received normal saline (2 ml/day, i.p.). Group two received a single dose of cisplatin (5 mg/kg, i.p.). Groups 3 to 5 received crocin (100, 200 and 400 mg/kg, i.p., respectively, for 4 consecutive days one hour before a single dose of cisplatin (5 mg/kg) only at the first day. Blood samples were taken out (on the fifth day) for measuring the level of urea and creatinine. The kidneys were removed for histopathological and biochemical examinations. Furthermore, 24-hour urinary factors were measured. RESULTS: Blood urea, creatinine and urinary glucose and protein concentrations in crocin-treated groups were significantly lower than those of cisplatin-treated group in a dose-dependent manner. Histopathological studies showed a massive damage in S3 segment of proximal tubules in cisplatin-treated group. No damage was observed in crocin-treated groups. Crocin treatment resulted in a significant and dose-dependent reduction in malondialdehyde concentration as compared to the cisplatin-treated group. Moreover, crocin produced a significant elevation in total thiol and glutathione peroxidase concentrations, as compared with cisplatin-treated group. CONCLUSION: The results of the present study suggest that crocin has a protective effect against cisplatin-induced acute renal failure and relative oxidative stress.