Abstract

Background: Colistin utilization has gradually increased worldwide with the rising of multidrug-resistant (MDR) gram-negative bacilli despite its nephrotoxicity. Lipid emulsion (LE) is widely used for the toxic overdose treatment of various drugs.

Objective: The aim of the present study is to evaluate the effect of lipid emulsion on the improvement of renal damage in colistin-induced nephrotoxicity with an experimental Sprague Dawley rat model.

Methods: Twenty-four male Sprague Dawley rats were initially assigned to 2 random groups. Sixteen rats were given a single dose of 20 mg/kg colistin, and eight rats received no medication (control group). Sixteen rats that were administered colistin were sub-divided into 2 groups. Group 1/LE rats (n = 8) were given 20 ml/kg solution of lipid emulsion, and group 2/S rats (n = 8) were given 20 ml/kg/day (i.p.) of 0.9% NaCl saline; both were administered for 10 days. Then tubular injury was evaluated histopathologically. Serum levels of blood urea nitrogen (BUN), Kidney Injury Molecule-1 (KIM-1), and creatinine were measured. Besides, malondialdehyde (MDA) levels were determined in tissue samples for the assessment of lipid peroxidation.

Results: The mean percent of tubular epithelial cell injury and tubular dilatation was found significantly higher in group 2/S than in control and group 1/LE (p < 0.0001 and < 0.001; respectively). KIM-1 and MDA levels were also statistically higher in group 2/S than in control and group 1/LE. (p < 0.0001 and < 0.0001; respectively). Additionally, serum BUN and creatinine levels of group 2/S were significantly greater than control and group 1/LE (p < 0.0001 and < 0.0001; respectively).

Conclusion: In this present study, we determined that colistin-induced proximal tubular damage was decreased histopathologically and serologically by the effect of lipid emulsion. Thus, our findings may guide future studies on the clinical use of colistin, particularly in MDR positive intensive care infections.

Keywords: Colistin, lipid emulsion, kidney injury molecule-1, nephrotoxicity, kidney/renal injury, rats.

Graphical Abstract