Abstract

Nitric oxide (NO) synthase inhibition increases hypertension and causes renal injury. Ferula gummosa is used in Iranian traditional medicine for treatment of several diseases and has been reported to exert a potent anti-inflammatory and antioxidant action. The aim of this investigation was to evaluate the renoprotective effects of hydroalcoholic extract of Ferula gummosa (HEG) on N omega-nitro-L-arginine methyl ester (L-NAME)-induced oxidative stress and inflammation and explore the mechanisms that link NO deficiency with altered renal heat shock protein (HSP70). Rats were injected intraperitoneally with L-NAME (10 mg/kg) to induce renal injury. Simultaneously, HEG (90 mg/kg) was administered by gastric gavage to L-NAME-treated rats for 6 days/week during an 8-week period. Renal thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), HSP70, plasma NO and total antioxidant capacity (TAC) were evaluated. The administration of L-NAME significantly increased renal TBARS, TNF-alpha, IL-6, HSP70 levels and decreased renal SOD activity, that these changes were accompanied by the reduced plasma NO and TAC levels. HEG administration decreased TBARS, HSP70, TNF-alpha and IL-6 levels and increased SOD activity in the kidney tissues of L-NAME treated rats (p<0.05). Also, plasma TAC level and NO bioavailability have been elevated after administration of HEG (p<0.05). These findings support that NO deficiency induces renal stress oxidative and inflammation, which markedly increased renal HSP70 and HEG could protect kidney against these damaging effects via its anti-oxidative, anti-inflammatory action and modulate renal HSP70.