Protective potential of curcumin in L-NAME-induced hypertensive rat model: AT1R, mitochondrial DNA synergy

Int J Physiol Pathophysiol Pharmacol. 2020 Oct 15;12(5):134-146. eCollection 2020.

Abstract

Background & objectives: Hypertension can be induced by inhibiting nitric oxide synthesis with L-NAME, which also has a role in oxidative stress. Curcumin has strong antioxidant property. Our aim was to examine the possible preventive role of curcumin on renal dysfunction secondary to hypertension.

Material & methods: Twenty-four adult male Albino rats were divided in four groups: normal (N); curcumin (C; received curcumin 100 mg/kg/day by oral gavage for 10 weeks); hypertensive (H; received L-NAME 40 mg/kg/day in their drinking water for 4 weeks); and hypertensive-curcumin (HC; received L-NAME and curcumin). Arterial blood pressure was evaluated non-invasively for 4 weeks. Rats were then sacrificed for assessment of oxidative stress (catalase, lipid peroxidase, reduced glutathione and superoxide dismutase), renal function and structure, and biomarkers of apoptosis (Bcl-2 and caspase-3). AT1R expression and renal mtDNA integrity were also assessed.

Results: Curcumin attenuated the effects of L-NAME on blood pressure and renal function. The renal histopathological changes observed in the L-NAME group were improved by curcumin administration. The expression of Bcl2 and caspase-3 was improved associated with downregulation of AT1R in curcumin treated groups. The antioxidant markers and mtDNA fragmentation show marked increase in hypertensive group which significantly decreased after curcumin treatment.

Conclusion: Curcumin improved blood pressure elevation renal dysfunction. These improvements mediated through anti-oxidant capabilities and downregulation of AT1R favoring reduced apoptosis and preserved mitochondrial DNA.

Keywords: AT1R; L-NAME; curcumin; mtDNA; oxidative stress; renal function.