Protective Effects of Carvedilol and Vitamin C against Azithromycin-Induced Cardiotoxicity in Rats via Decreasing ROS, IL1-β, and TNF-α Production and Inhibiting NF-κB and Caspase-3 Expression.
The Food and Drug Administration recently warned of the fatal cardiovascular risks of azithromycin in humans. In addition, a recently published study documented azithromycin-induced cardiotoxicity in rats. This study aimed to justify the exact cardiovascular events accompanying azithromycin administration in rats, focusing on electrocardiographic, biochemical, and histopathological changes. In addition, the underlying mechanisms were studied regarding reactive oxygen species production, cytokine release, and apoptotic cell-death. Finally, the supposed protective effects of both carvedilol and vitamin C were assessed. Four groups of rats were used: (1) control, (2) azithromycin, (3) azithromycin + carvedilol, and (4) azithromycin + vitamin C. Azithromycin resulted in marked atrophy of cardiac muscle fibers and electrocardiographic segment alteration. It increased the heart rate, lactate dehydrogenase, creatine phosphokinase, malondialdehyde, nitric oxide, interleukin-1 beta (IL1-β), tumor necrosis factor alpha (TNF-α), nuclear factor kappa beta (NF-κB), and caspase-3. It decreased reduced glutathione, glutathione peroxidase, and superoxide dismutase. Carvedilol and vitamin C prevented most of the azithromycin-induced electrocardiographic and histopathological changes. Carvedilol and vitamin C decreased lactate dehydrogenase, malondialdehyde, IL1-β, TNF-α, NF-κB, and caspase-3. Both agents increased glutathione peroxidase. This study shows that both carvedilol and vitamin C protect against azithromycin-induced cardiotoxicity through antioxidant, immunomodulatory, and antiapoptotic mechanisms.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Elkandarh, Jeddah 21589, Saudi Arabia; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Nagla A
NA
El-Shitany
Department of Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt.
Karema
K
El-Desoky
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D001205:Ascorbic Acid / Q000494:pharmacology*; D017963:Azithromycin / Q000633:toxicity*; D002227:Carbazoles / Q000494:pharmacology*; D066126:Cardiotoxicity / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D000077261:Carvedilol; D053148:Caspase 3 / Q000378:metabolism*; D004562:Electrocardiography / Q000187:drug effects; D053583:Interleukin-1beta / Q000096:biosynthesis; D008297:Male; D016328:NF-kappa B / Q000096:biosynthesis; D011412:Propanolamines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D002227:Carbazoles; D053583:Interleukin-1beta; D016328:NF-kappa B; D011412:Propanolamines; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000077261:Carvedilol; D017963:Azithromycin; D053148:Caspase 3; D001205:Ascorbic Acid