Abstract
Purpose: The aim of the study explores probable toxic effects of vancomycin on kidney and analysis of the probable protective effects of melatonin.
Materials and Methods: In this study, rats were randomly divided into 4 groups: the control group; the melatonin (10 mg/kg/day) group; the vancomycin-treated (200 mg/kg) group; and the vancomycin (200 mg/kg) + melatonin (10 mg/kg/day) group. Rats in the treatment group were given two doses of vancomycin a day with an interval of seven consecutive days and melatonin (10 mg/kg/day) once daily for seven consecutive days. The experiment was continued for 15 days. In each group, seven rats were grouped together. 15 days after the experiment, the rats were sacrificed under anesthesia and among all groups. Kidney tissues were collected and processed for further TNF- expression analysis, as well as histological analyses such as hematoxylin and eosin (H&E), Masson's tricrom, and Periodic acid schiff (PAS) staining to assess pathological severity. In addition, a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to evaluate apoptosis.
Results: While vancomycin upregulated TNF-α expression, melatonin reduced levels of TNF-α immunoreactivity intensity and clearly improved pathological severity in rat kidneys. Further, melatonin significantly inhibited vancomycin-induced TUNEL-positive cell numbers.
Conclusion: Melatonin has protective activity against vancomycin-induced pro-inflammatory and proapoptotic effects in kidneys during organ preservation time and improves kidney function.
Subject
General Earth and Planetary Sciences,General Environmental Science
Reference41 articles.
1. 1. Basarslan F, Yilmaz N, Ates S, Ozgur T, Tutanc M, Motor VK, et al. Protective effects of thymoquinone on vancomycin-induced nephrotoxicity in rats. Hum Exp Toxicol. 2012;31:726–733.
2. 2. Humanes B, Jado JC, Camano S, López-Parra V, Torres AM, Álvarez-Sala LA, et al. Protective effects of cilastatin against vancomycin-induced nephrotoxicity. Biomed Res Int. 2015;2015:704382.
3. 3. Álvarez R, López Cortés LE, Molina J, Cisneros JM, Pachón J. Optimizing the clinical use of vancomycin. Antimicrob Agents Chemother. 2016;60(5):2601–2609.
4. 4. Martin JH, Norris R, Barras M, Roberts J, Morris R, Doogue M, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of health-system pharmacists, the infectious diseases society of America, and the society of infectious diseases pharmacists. Clin Biochem Rev. 2010;31:21–24.
5. 5. Van Hal SJ, Paterson DL, Lodise TP. Systematic review and meta-analysis of vancomycin-induced nephrotoxicity asso- ciated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter. Antimicrob Agents Chemother. 2013; 57:734–744.