Protective effects of lutein against vancomycin-induced acute renal injury in mice via upregulation of peroxisome proliferatoractivated receptor gammauclear factor erythroid 2-related factor 2 and inhibition nuclear factor-kappaB/caspase 3
10.4196/kjpp.2021.25.4.321
- Author:
Promise M. EMEKA
1
;
Sahibzada T. RASOOL
;
Mohamed A. MORSY
;
Mohamed I. HAIRUL ISLAM
;
Muhammad S. CHOHAN
Author Information
1. Departments of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
- Publication Type:Original Article
- From:The Korean Journal of Physiology and Pharmacology
2021;25(4):321-331
- CountryRepublic of Korea
- Language:English
-
Abstract:
Vancomycin, an antibiotic used occasionally as a last line of treatment for methicillin-resistant Staphylococcus aureus, is reportedly associated with nephrotoxicity. This study aimed at evaluating the protective effects of lutein against vancomycin-induced acute renal injury. Peroxisome proliferator-activated receptor gamma (PPARγ) and its associated role in renoprotection by lutein was also examined. Male BALB/c mice were divided into six treatment groups: control with normal saline, lutein (200 mg/kg), vancomycin (250 mg/kg), vancomycin (500 mg/kg), vancomycin (250 mg/kg) with lutein, and vancomycin (500 mg/kg) with lutein groups; they were euthanized after 7 days of treatment. Thereafter, samples of blood, urine, and kidney tissue of the mice were analyzed, followed by the determination of levels of N-acetyl-β-D-glucosaminidase (NAG) in the urine, renal creatine kinase; protein carbonyl, malondialdehyde, and caspase-3 in the kidney; and the expression of PPARγ, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-kappaB (NF-κB) in renal tissue. Results showed that the levels of protein carbonyl and malondialdehyde, and the activity of NAG, creatine kinase and caspase-3, were significantly increased in the vancomycin-treatment groups. Moreover, the levels of Nrf2 significantly decreased, while NF-κB expression increased. Lutein ameliorated these effects, and significantly increased PPARγ expression. Furthermore, it attenuated vancomycin-induced histological alterations such as, tissue necrosis and hypertrophy. Therefore, we conclude that lutein protects against vancomycin-induced renal injury by potentially upregulating PPARγ/Nrf2 expression in the renal tissues, and consequently downregulating the pathways: inflammation by NF-κB and apoptosis by caspase-3.
