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Abstract
Gentamicin, belonging to the aminoglycosides, possesses the greatest nephrotoxic effect of all other antibiotics from this group. On the other hand, pioglitazone, which represents peroxisome proliferator-activated receptor γ (PPARγ) agonist recently showed antiinflamatory, antioxidative effects, amelioration of endothelial dysfunction etc. Therefore, the goal of our study was to investigate the effects of pioglitazone on kidney injury in an experimental model of gentamicin-induced nephrotoxicity in rats. These effects were observed by following values of biochemical (serum urea and creatinine) parametars, total histological kidney score, urine level of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) as well as parametars of oxidative stress (malondialdehyde, superoxide dismutase, catalase, total oxidant status, total antioxidant status, oxidative stress index and advanced oxidation protein products). It seems that pioglitazone protects the injured rat kidney in a U-shaped manner. Medium dose of pioglitazone (1 mg/kg, i.p.) was protective regarding biochemical (serum urea and creatinine), total histological score and the values of kidney injury molecule-1 (KIM-1) (P < 0.05 vs. control group, i.e. rats injected with gentamicin only). This finding could be of great importance for the wider use of aminoglycosides, with therapy that would reduce the occurrence of serious adverse effects, such as nephrotoxicity and acute renal failure.
Highlights
Aminoglycosides are a group of antibiotics, which are used for treatment of serious infections worldwide
When results were compared between gentamicin and the groups where gentamicin and pioglitazone were at the same time administrated, no difference was found (Fig. 1B)
Our study showed that the administration of gentamicin at the dose of 100 mg/kg/day for 7 days i.p., successfully induced nephrotoxicity in all treated animals
Summary
Aminoglycosides are a group of antibiotics, which are used for treatment of serious infections worldwide. The exact mechanism of gentamicin-induced renal damage has not been fully understood, but it seems that generation of reactive oxygen species (ROS) and inflammation have a crucial role in pathogenesis of kidney injury. For this reason, drugs with promising antiinflamatory, antioxidative and nephroprotective properties were in focus of examination in numerous preclinical and clinical studies in the past decade[4,5]. Recent study showed that pioglitazone reduced renal injury in experimental diabetic rats through its antiinflammatory actions, including inhibition of Nuclear factor kappa B (NF-κB) activation and macrophage infiltration in the kidney[8]. The goal of our study was to investigate the effects of pioglitazone on kidney injury in an experimental model of gentamicin-induced nephrotoxicity in rats
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