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AZT-Induced Oxidative Cardiovascular Toxicity: Attenuation by Mg-Supplementation

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Cardiovascular effects of chronic AZT treatment on SD male rats (185 g) fed either a normal Mg diet (0.1% MgO) or a high Mg diet (0.6% MgO) were examined. AZT treatment (1 mg/ml drinking water) for 3 weeks led to a 5.5-fold (0.88 ± 0.11 nmol/min/106 cells, P < 0.05) elevation in neutrophil basal activity of O2 − production versus controls (0.16 ± 0.03 nmol/min, assayed ex vivo as SOD-inhibitable cytochrome c reduction). Concomitantly, plasma 8-isoprostane and PGE2 levels rose 2.1-fold and 3-fold (both P < 0.05), respectively, compared to control; however, RBC GSH decreased 28% (P < 0.02) with GSSG content increased 3-fold, indicative of systemic oxidative stress. High Mg diet substantially attenuated the AZT-induced neutrophil activation by 70% (0.26 ± 0.05 nmol/min, P < 0.05); reduced plasma 8-isoprostane and PGE2 to levels comparable to normal; and RBC GSH was restored back to 92% of control. AZT alone caused moderate, but significant vascular inflammatory lesions in the heart (assessed by H&E staining). Immunohistochemical staining revealed significantly higher (about 4-fold) infiltration of CD11b positive cells (WBC surface marker) in the atria and ventricles of AZT-treated rats. However, these inflammatory pathological markers were minimal in samples of rats treated with AZT plus high Mg diet. Moreover, AZT alone significantly (P < 0.02) decreased rat weight gain by 21% at 3 weeks; Mg-supplementation completely prevented (P < 0.05) the weight gain loss due to AZT intake. It is concluded that high dietary Mg may provide beneficial effects against AZT toxicity due to its systemic antioxidative/anti-inflammatory properties.

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Acknowledgments

The authors wish to thank Kenny Landgraf for his excellent technical assistance. This study was supported by NIH R21-AT003993 & NIH RO1-HL-65178.

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  1. Department of Biochemistry & Molecular Biology, Division of Experimental Medicine, The George Washington University Medical Center, 2300 Eye Street, N.W. Ross Hall, Rm 443, Washington, DC, 20037, USA

    I. Tong Mak, Joanna J. Chmielinska, Jay H. Kramer & William B. Weglicki

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  1. I. Tong Mak
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Correspondence to I. Tong Mak.

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Mak, I.T., Chmielinska, J.J., Kramer, J.H. et al. AZT-Induced Oxidative Cardiovascular Toxicity: Attenuation by Mg-Supplementation. Cardiovasc Toxicol 9, 78–85 (2009). https://doi.org/10.1007/s12012-009-9040-8

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