Curcumin Supplementation Alleviates Polymyxin E-Induced Nephrotoxicity

Abstract

Background

The last-line agent for gram-negative bacteria that have developed resistance towards commonly used antibiotics is polymyxin E (PolyE). The renal toxicity attributed to this agent limits its use, proper dosing, and eventually its clinical efficacy. Although the exact mechanism of PolyE-induced nephrotoxicity is not obvious, some investigations suggest the role of oxidative stress and its associated events in this complication. Curcumin (CUR) is a potent antioxidant molecule. The aim of the current investigation was the evaluation of the potential nephroprotective properties of CUR in PolyE-treated mice.

Materials and Methods

Mice were randomly allocated into five groups (n = 8 per group). PolyE (15 mg/kg/day, i.v, for 7 days) alone or in combination with CUR (10, 100 and 200 mg/kg, i.p) were administered to mice. Renal injury biomarkers, in addition to markers of oxidative stress and kidney histopathological alterations, were evaluated.

Results

Plasma creatinine (Cr) and blood urine nitrogen (BUN) significantly raised in PolyE group. Oxidative stress biomarkers consisting of reactive oxygen species (ROS) and lipid peroxidation (LPO) also increased, and concomitantly GSH and antioxidant capacity of renal cells significantly decreased following the use of PolyE. Interstitial nephritis, tissue necrosis, and glomerular atrophy were all induced by the use of PolyE in the mice kidney. CUR (10, 100, and 200 mg/kg, i.p) treatment alleviated PolyE-induced oxidative stress and histopathological alterations in the kidney tissue significantly.

Conclusion

According to the results of this study, CUR has a protective role against renal toxicity induced by PolyE. Hence, more research is necessary until this compound could be clinically applicable to alleviate PolyE-induced renal injury.

Keywords:

• antibiotics
• mitochondrial impairment
• nephrotoxicity
• oxidative stress

Acknowledgments

This investigation was financially supported by the Vice-Chancellor of Research Affairs of Shiraz University of Medical Sciences (Grant 14397/14823). Authors thank the Pharmaceutical Sciences Research Center (PSRC) of Shiraz University of Medical Sciences for providing technical facilities to carry out this study.

Author Contributions

AV and RH conceived and planned the experiments. RH and ZK performed the measurements and contributed to sample preparation. AV and RH were involved in the interpretation of the results. All authors contributed toward drafting and revising the paper, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that there is no conflict of interest.