Cardiac pathologic effects of azidothymidine (AZT) in Mg-deficient mice

Cardiovascular Toxicology
I Tong MakChristian C Haudenschild

Abstract

Treatment of HIV with AZT (zidovudine) may have toxic side effects as a result of multiple mechanisms. It is known that patients with AIDS may suffer from magnesium deficiency (MgD). We studied selected biochemical and histopathologic consequences of AZT administration (0.7 mg/mL in drinking water) with concurrent Mg-deficient (20% of normal) diet in male C57Bl/6N mice for 3 wk. Significant decreases in red blood cell glutathione (GSH) were evident in the Mg-deficient mice with or without AZT treatment, suggesting compromised antioxidant capacity in the blood. Although MgD alone led to a 1.9-fold increase in plasma thromboxane B(2) (TXB(2), derived from the highly vasoconstrictive TXA(2)), AZT + MgD increased the TXB(2) level 3.5-fold. AZT (+/-MgD) provoked prominent hepatic damage expressed by distortion of lobular architecture, nuclear and cellular swelling, and inflammatory lesions and loss of hepatocytes. AZT alone caused mild cardiac lesions, resulting in partial cardiac fibrosis, especially in the atrium. AZT + MgD caused only scattered small-size cardiac lesions consisting of microscopic foci of inflammatory infiltrates in the ventricles but led to more prominent lesions, fibrosis, and scars in the atrium. MgD or AZT alo...Continue Reading

Citations

Jun 2, 2009·Cardiovascular Toxicology·I Tong MakWilliam B Weglicki
Apr 29, 2009·Laboratory Investigation; a Journal of Technical Methods and Pathology·James J KohlerWilliam Lewis
Sep 21, 2013·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·I Tong MakWilliam B Weglicki

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