Protective Effect of Neutral Electrolyzed Saline on Gentamicin-Induced Nephrotoxicity: Evaluation of Histopathologic Parameters in a Murine Model

Abstract

Background and Objectives: Gentamicin (GM) is a nephrotoxic aminoglycoside. Neutral electrolyzed saline (SES) is a compound with anti-inflammatory, antioxidant, and immunomodulatory properties. The objective of the present study was to evaluate whether kidney damage by GM can be prevented and/or reversed through the administration of SES. Materials and Methods: The study was carried out as a prospective, single-blind, five-arm, parallel-group, randomized, preclinical trial. The nephrotoxicity model was established in male BALB/c mice by administering GM at a dose of 100 mg/kg/day intraperitoneally for 30 days, concomitantly administering (+) SES or placebo (physiologic saline solution), and then administering SES for another 30 days after the initial 30 days of GM plus SES or placebo. At the end of the test, the mice were euthanized, and renal tissues were evaluated histopathologically. Results: The GM + placebo group showed significant tubular injury, interstitial fibrosis, and increased interstitial infiltrate of inflammatory cells compared with the group without GM. Tubular injury and interstitial fibrosis were lower in the groups that received concomitant GM + SES compared with the GM + placebo group. SES administration for 30 days after the GM administration periods (GM + placebo and GM + SES for 30 days) did not reduce nephrotoxicity. Conclusions: Intraperitoneal administration of SES prevents gentamicin-induced histologic nephrotoxicity when administered concomitantly, but it cannot reverse the damage when administered later.

Keywords: anti-inflammatory agents; gentamicin; hypochlorous acid; kidney; reactive oxygen species; toxicity.

Figure 1

Schematic representation of the study. GM: gentamicin, SES: neutral electrolyzed saline, IL-6: interleukin 6.

Figure 2

Effect of neutral electrolyzed saline (SES) on histopathologic changes in gentamicin (GM)-induced nephrotoxicity in the Balb/c mouse model. Placebo-after placebo group; GM + placebo-after placebo group; GM + placebo-after SES group; GM + SES-after SES group; and GM + SES-after placebo group. Yellow arrows show areas of tubular injury (flattening of the tubular epithelium, cellular fragments within their lumens, blebbing of the apical membrane into the tubular lumen, and loss of some nuclei), interstitial fibrosis, and interstitial inflammatory cell infiltration in the appropriate section. The GM + SES-after SES and GM + SES-after placebo groups showed less tubular injury and interstitial fibrosis compared with the GM + placebo-after placebo group. In addition, the GM + SES-after placebo and GM + SES-after SES groups had more interstitial inflammatory cell infiltrate than the GM + placebo-after placebo group. Tubular injury and interstitial inflammatory cell infiltrate: hematoxylin–eosin, x400; interstitial fibrosis: Masson’s trichrome, ×100; n = 53.