Vitamin C prevents zidovudine-induced NAD(P)H oxidase activation and hypertension in the rat

Papparella, Italia; Ceolotto, Giulio; Bertó, Laura; Cavalli, Maurizio; Bova, Sergio; Cargnelli, Gabriella; Ruga, Ezia; Milanesi, Ornella; Franco, Lorenzo; Mazzoni, Martina; Petrelli, Lucía; Nussdorfer, Gastone G.; Semplicini, Andrea

doi:10.1016/j.cardiores.2006.10.010

Cited by 40 publications

(31 citation statements)

References 43 publications

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“…For example, in rat models of hypertension and renal dysfunction, treatment with vitamins C and E prevented renal inflammation and decreased arterial pressure, thus improving renal function (323). However, vitamin E treatment in hemodialysis patients with chronic kidney disease did not reduce oxidative protein modifications and lipid peroxidation (181), although a reduction in oxidative stress markers (60,185) and improvements in endothelial function (356) inhibition of NADPH oxidase activity (230). In contrast, several clinical trials, such as the long-term trial performed by Sesso et al, have found that vitamins C and E have no preventive effect with regard to cardiovascular events, including coronary revascularization, non-lethal myocardial infarction, stroke, or CVD death (54,178,288).…”

Section: Non-targeted Antioxidant Treatmentsmentioning

confidence: 99%

Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

Apostolova

Víctor

2015

Antioxidants & Redox Signaling

231

147

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Mitochondrial function and specifically its implication in cellular redox/oxidative balance is fundamental in controlling the life and death of cells, and has been implicated in a wide range of human pathologies. In this context, mitochondrial therapeutics, particularly those involving mitochondria-targeted antioxidants, have attracted increasing interest as potentially effective therapies for several human diseases. For the past 10 years, great progress has been made in the development and functional testing of molecules that specifically target mitochondria, and there has been special focus on compounds with antioxidant properties. In this review, we will discuss several such strategies, including molecules conjugated with lipophilic cations (e.g., triphenylphosphonium) or rhodamine, conjugates of plant alkaloids, amino-acid-and peptide-based compounds, and liposomes. This area has several major challenges that need to be confronted. Apart from antioxidants and other redox active molecules, current research aims at developing compounds that are capable of modulating other mitochondria-controlled processes, such as apoptosis and autophagy. Multiple chemically different molecular strategies have been developed as delivery tools that offer broad opportunities for mitochondrial manipulation. Additional studies, and particularly in vivo approaches under physiologically relevant conditions, are necessary to confirm the clinical usefulness of these molecules. Antioxid. Redox Signal. 22, 686-729.

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Section: Non-targeted Antioxidant Treatmentsmentioning

confidence: 99%

Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

Apostolova

Víctor

2015

Antioxidants & Redox Signaling

231

147

View full text Add to dashboard Cite

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“…It is probable that the differences in the susceptibility to AZT among different cells accounts for these discrepancies. It is to be recalled that there is evidence that cytotoxic effects of AZT depend on the rise in the ROS production (10,12,(30)(31)(32). Accordingly, the treatment with the anti-oxidant vitamin C is able to prevent AZT-induced toxic lesions in rat cardiomyocytes (10,12).…”

Section: Discussionmentioning

confidence: 99%

“…It is to be recalled that there is evidence that cytotoxic effects of AZT depend on the rise in the ROS production (10,12,(30)(31)(32). Accordingly, the treatment with the anti-oxidant vitamin C is able to prevent AZT-induced toxic lesions in rat cardiomyocytes (10,12). The adrenal gland is one of the organs with the highest concentration of vitamin C in the mammalian body (33), which not only is a cofactor required for both steroid-hormone and catecholamine synthesis, but also prevents the destructive effects of lipid peroxidation on adrenocortical mitochondria cytocrome P450 (34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have shown that prolonged administration of AZT induces heart toxicity both in humans and experimental animals, mainly due to mitochondrial dysfunctions in myocardiocytes (8)(9)(10)(11)(12), but the effects of this drug on adrenal function have not yet been studied. Therefore, it seems important to investigate, in vivo and in vitro, the effects of AZT on the structure and function of the adrenal cortex in the rat, in order to evaluate the possibility that adrenal dysfunction occurring in HIV patients is, at least partly, a side-effect of the therapy with this antiretroviral drug.…”

Section: Introductionmentioning

confidence: 99%

“…Rats were divided into two equal groups. One group was treated with AZT (100 mg/kg per day) dissolved in drinking water (11,12) for 4 months, and the other group was untreated and served as a control. Animals were decapitated at 11:00 a.m., and their trunk blood was collected with apoprotin (70 mg/ml) and EDTA (1 mg/ml); plasma was separated and stored at -80˚C.…”

Section: Introductionmentioning

confidence: 99%

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Prolonged zidovudine administration induces a moderate increase in the growth and steroidogenic capacity of the rat adrenal cortex

Tortorella

Guidolin²,

Petrelli³

et al. 2009

Int J Mol Med

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Abstract. Zidovudine (AZT) is an antiretroviral drug widely used in the treatment of human immunodeficiency virus (HIV)-infected patients, whose prolonged administration was found to cause toxic lesions in cardiomyocytes in humans and experimental animals. Alterations in adrenocortical secretion were frequently observed in HIV patients, but it is not clear whether medication is involved in the production of these complications. Hence, we studied in vivo and in vitro, the effects of AZT on the rat adrenal cortex. The prolonged AZT administration (100 mg/kg per day for 4 months) did not cause overt qualitative morphological alterations of adrenocortical cells, which, however, underwent a net hypertrophy. Hypertrophy is associated with increases in the volume and surface area per cell of the mitochondrial compartment and smooth endoplasmic reticulum (where the enzymes of steroid synthesis are located), and a marked decrease in the volume of the lipiddroplet compartment (where cholesterol and its esters, the precursors of steroid hormones, are stored). AZT chronic treatment induced rises in the plasma concentrations of aldosterone and corticosterone, and in the basal and ACTHstimulated in vitro secretion of these hormones from adrenal slices. The 24-h exposure to AZT (10 -5 M) did not significantly affect either secretory activity or proliferation and apoptotic rates of cultured rat adrenocortical cells. Taken together, these findings suggest that AZT chronic treatment enhances the growth and steroidogenic capacity of rat adrenal cortex, probably by activating the central branch of the hypothalamicpituitary-adrenal axis. The toxic activity of AZT is thought to depend on increased production of ROS. On these grounds, it is likely that the lack of toxic effect of AZT on adrenocortical cells is due to their very elevated content in vitamin C, which prevents the deleterious effect of the AZT-induced increase in intracellular ROS production.

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An abnormal gene expression of the β-adrenergic system contributes to the pathogenesis of cardiomyopathy in cirrhotic rats

et al. 2008

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Decreased cardiac contractility and ␤-adrenergic responsiveness have been observed in cirrhotic cardiomyopathy, but their molecular mechanisms remain unclear. To study ␤-adrenergic-stimulated contractility and ␤-adrenergic gene expression patterns, 20 Wistar Kyoto rats were treated with carbon tetrachloride to induce cirrhosis and 20 rats were used as controls. Left ventricular contractility was recorded in electrically driven isolated hearts perfused at constant flow with isoproterenol (10 ؊10 to 10 ؊6 M). A cardiac gene expression profile was obtained using a microarray for the myocyte adrenergic pathway. The cardiac contractility maximal response to isoproterenol was significantly reduced in cirrhotic rats in comparison to control rats, whereas the half-maximal effective concentration was not different. In cirrhotic rats, cardiac gene expression analysis showed a significant overexpression of G protein alpha-inhibiting subunit 2 (G␣ i2 ), cyclic nucleotide phosphodiesterase (PDE2a), regulator of G-protein signaling 2 (RGS2), and down-expression of adenylate cyclase (Adcy3). These results indicate that overexpression of G␣ i2 , PDE2a, and RGS2 down-regulates the ␤-adrenergic signaling pathway, thus contributing to the pathogenesis of cirrhotic cardiomyopathy. (HEPATOLOGY 2008;48:1913-1923

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Vitamin C prevents zidovudine-induced NAD(P)H oxidase activation and hypertension in the rat

Abstract: Chronic AZT administration increases blood pressure and promotes cardiovascular damage through a NAD(P)H oxidase-dependent mechanism that involves PKC delta. Vitamin C antagonizes these adverse effects of AZT in the cardiovascular system.

Cited by 40 publications

References 43 publications

Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

Prolonged zidovudine administration induces a moderate increase in the growth and steroidogenic capacity of the rat adrenal cortex

An abnormal gene expression of the β-adrenergic system contributes to the pathogenesis of cardiomyopathy in cirrhotic rats

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