Curcumin prevents HIV protease inhibitor ritonavir-induced vascular injury and superoxide anion production in porcine coronary arteries

Abstract

Introduction: HIV protease inhibitor ritonavir (RTV) may induce vascular dysfunction through oxidative stress. The objective of this study was to determine whether a dietary antioxidant curcumin could prevent coronary arteries from RTV-induced injury. Methods: Porcine coronary arteries were incubated with RTV and/or curcumin for 24 hours. Vasomotor function was studied with a myograph tension system in response to thromboxane A2 analogue U46619 (contraction), and bradykinin (endothelium-dependent relaxation). Superoxide anion levels were determined by lucigenin enhanced chemiluminescence. Results: In response to U46619, the control vessels showed a 71% reduction (p < 0.001, t-test). The combination of RTV and curcumin showed a vessel tension similar to controls. In response to bradykinin, the control vessel rings relaxed by 70.80%, while RTV treated vessels only relaxed by 29.25%, which showed a 59% reduction as compared to controls (p < 0.001, t-test). Curcumin plus RTV showed 54.20% of vasorelaxation, respectively. Superoxide anion level in the RTV-treated group was increased by 47%, as compared to controls (P < 0.05, t-test). Curcumin treatment significantly inhibited RTV induced superoxide anion production. Conclusions: HIV protease inhibitor RTV significantly decreases smooth muscle cell contractivity and endothelium-dependent vasorelaxation, but increases superoxide anion production in porcine coronary arteries. Curcumin can effectively inhibit RTV-induced vascular injury and oxidative stress.