The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Protective effects of lutein against vancomycin-induced acute renal injury in mice via upregulation of peroxisome proliferator-activated receptor gamma/nuclear factor erythroid 2-related factor 2 and inhibition nuclear factor-kappaB/caspase 3

  • Emeka, Promise M. (Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University) ;
  • Rasool, Sahibzada T. (Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University) ;
  • Morsy, Mohamed A. (Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University) ;
  • Islam, Mohamed I. Hairul (Department of Biological Sciences, College of Science, King Faisal University) ;
  • Chohan, Muhammad S. (Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University)
  • Received : 2020.10.26
  • Accepted : 2021.04.05
  • Published : 2021.07.01
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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.

Keywords

Acknowledgement

We hereby wish to thank Deanship of Scientific Research, King Faisal University, Saudi Arabia for supporting this research. Also we wish to acknowledge Mr. Tameem Alyahian, our Laboratory Supervisor, for his assistance. We also acknowledge Mr. Sami Al-Qaimi for helping us with the procurement of chemicals. This research project was funded by the Deanship of Scientific Research, King Faisal University, Saudi Arabia (grant number: 140237).

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