Expression profile of markers of oxidative stress, injury and apoptosis in anti‐tuberculosis drugs induced nephrotoxicity. Issue 7 (15th April 2019)

• Record Type: Journal Article
• Authors: Sharma, Radhika; Battu, Priya; Singla, Mandakini; Goyal, Neha; Sharma, Vijay L
• Is Part Of: Nephrology. Volume 24:Issue 7(2019)
• Page Start: 689
• Page End: 695
• Publication Date: 2019-04-15
• Subjects: antioxidants -- apoptosis -- drug induced nephrotoxicity -- histology -- kidney markers; Nephrology -- Periodicals; Kidneys -- Diseases -- Periodicals; Nephrologists -- Periodicals; 616.61; 616.61
• DOI: 10.1111/nep.13399
• Languages: English
• ISSNs: 1320-5358

Abstract

ABSTRACT: Aim: Isoniazid (INH), Rifampicin (RIF) and Pyrazinamide (PZA) are part of first‐line anti‐tuberculosis therapy used against infection caused by Mycobacterium tuberculosis . However, these drugs are known to be potentially harmful as these are associated with numerous side effects and when taken together their harmful outcomes are elevated in a synergistic manner. Identification of possible mechanism underlying RIF + INH + PZA induced nephrotoxicity may be advantageous in developing strategies to prevent their toxic implications. Methods: In this study rats were distributed in two groups of six each: Control (tap water) and Toxicant (INH + RIF + PZA) in dosage derived through extrapolation from human dosage for 28 days once in a day. Antioxidant activity and histology of kidney were examined. In addition, apoptosis was also studied using pro and anti‐apoptotic markers and TUNEL staining to check nephrotoxicity. Results: Findings indicated that combined (INH, RIF and PZA) 28 day exposure in Wistar rats caused increase in number of free radicals/ reactive oxygen species which further cause changes in levels of enzymatic antioxidants such as glutathione, Superoxide dismutase, Catalase, and Glutathione‐s‐transferase. Altered content of pro (BAD&BAX) and anti‐apoptotic genes (BCL‐2&BCL2L1) genes, TUNEL positive cells and DNA fragmentation emphasized involvement of apoptosis. Conclusion: This study concluded that nephrotoxicity is accompanied during combinational anti‐tuberculosis drug therapy. Summary at a Glance: The authors reported the mechanisms of nephrotoxicity induced by combination of anti‐tuberculosis drugs, Isoniazid (INH), Rifampicin (RIF) and Pyrazinamide (PZA), in experimental rats. The findings will contribute to a better understanding of the kidney toxicity caused by three common anti‐tuberculosis drugs.