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- Title
Vitamin C prevents zidovudine-induced NAD(P)H oxidase activation and hypertension in the rat
- Authors
Papparella, Italia; Ceolotto, Giulio; Berto, Laura; Cavalli, Maurizio; Bova, Sergio; Cargnelli, Gabriella; Ruga, Ezia; Milanesi, Ornella; Franco, Lorenzo; Mazzoni, Martina; Petrelli, Lucia; Nussdorfer, Gastone G.; Semplicini, Andrea
- Abstract
Abstract: Objective: Cardiovascular risk is increased among HIV-infected patients receiving antiretroviral therapy due to the development of hypertension and metabolic abnormalities. In this study, we investigated the effects of long-term treatment with zidovudine (AZT) and vitamin C, alone and in combination, on blood pressure and on the chain of events linking oxidative stress to cardiac damage in the rat. Methods: Six adult Wistar Kyoto rats received AZT (1 mg/ml) in the drinking water for 8 months, six vitamin C (10 g/kg of food) and AZT, six vitamin C alone, and six served as controls. Results: AZT increased systolic blood pressure, expression of gp91phox and p47phox subunits of NAD(P)H oxidase, and protein kinase C (PKC) δ activation and reduced antioxidant power of plasma and cardiac homogenates. AZT also caused morphological alterations in cardiac myocyte mitochondria, indicative of functional damage. All of these effects were prevented by vitamin C. Conclusion: Chronic AZT administration increases blood pressure and promotes cardiovascular damage through a NAD(P)H oxidase-dependent mechanism that involves PKC δ. Vitamin C antagonizes these adverse effects of AZT in the cardiovascular system.
- Subjects
WATER-soluble vitamins; VITAL signs; HIV-positive persons; PROTEIN kinases
- Publication
Cardiovascular Research, 2007, Vol 73, Issue 2, p432
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1016/j.cardiores.2006.10.010