Pioglitazone attenuates kidney injury in an experimental model of gentamicin-induced nephrotoxicity in rats

• Published in: Scientific reports Vol. 9; no. 1; pp. 13689 - 10
• Main Authors: Medić, Branislava, Stojanović, Marko, Rovčanin, Branislav, Kekić, Dušan, Škodrić, Sanja Radojević, Jovanović, Gordana Basta, Vujović, Katarina Savić, Divac, Nevena, Stojanović, Radan, Radenković, Miroslav, Prostran, Milica
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.09.2019; Nature Publishing Group
• Subjects: 101/58; 13/51; 14/28; 631/45/881; 64; 692/308/2778; 96/63; Animals; Anti-Bacterial Agents - adverse effects; Antibiotics; Antioxidants; Catalase; Catalase - metabolism; Creatinine; Creatinine - metabolism; Gelatinase; Gentamicin; Gentamicins - adverse effects; Humanities and Social Sciences; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Kidney - drug effects; Kidney - metabolism; Kidney Diseases - chemically induced; Kidney Diseases - drug therapy; Kidney Diseases - metabolism; Kidneys; Lipocalin; Male; Malondialdehyde; Malondialdehyde - metabolism; multidisciplinary; Oxidation; Oxidative stress; Oxidative Stress - drug effects; Pioglitazone; Pioglitazone - pharmacology; Pioglitazone - therapeutic use; Protective Agents - pharmacology; Protective Agents - therapeutic use; Rats; Rats, Wistar; Renal failure; Science; Science (multidisciplinary); Superoxide dismutase; Superoxide Dismutase - metabolism; Urea; Urine
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-49835-1

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.