Atorvastatin prevents gentamicin-induced renal damage in rats through the inhibition of p38-MAPK and NF-kappaB pathways.
OBJECTIVE
Gentamicin (GM) is still considered to be an important antibiotic against life-threatening, gram-negative bacterial infections despite its known nephrotoxic effects. We aimed to evaluate the potential protective effect of atorvastatin (ATO) against GM-induced nephrotoxicity in rats.


METHODS
The rats were randomly divided into five groups of six animals each: control, GM (100 mg/kg/day), ATO (10 mg/kg/day), GM + ATO, and GM + Vehicle. Kidney function tests, tissue oxidative stress parameters, and histopathological and immunohistochemical studies clarified GM nephrotoxicity.


RESULTS
GM caused a marked reduction in renal functions and increased oxidative stress parameters. Histopathological examination revealed tubular necrosis especially in the renal cortex in GM rats. On immunohistochemical evaluation, GM rat showed more intense expressions of mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-kappaB), and inducible nitric oxide synthase (iNOS) compared with control. Kidney function tests and tissue oxidative stress parameters were normalized in the GM + ATO group. Histopathological and immunohistochemical pictures were also greatly ameliorated.


CONCLUSIONS
ATO acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GM via the inhibition of MAPK and NF-kappaB signaling pathways and iNOS expression.
Ozbek
Emin
E
Bezm-i Alem Valide Sultan Vakif Gureba Research and Education Hospital, Department of Urology, Istanbul, Turkey.
Cekmen
Mustafa
M
Ilbey
Yusuf Ozlem
YO
Simsek
Abdulmuttalip
A
Polat
Emre Can
EC
Somay
Adnan
A
D000704:Analysis of Variance; D000818:Animals; D000069059:Atorvastatin; D016009:Chi-Square Distribution; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000378:metabolism; D005839:Gentamicins / Q000494:pharmacology; D006538:Heptanoic Acids / Q000494:pharmacology*; D007150:Immunohistochemistry; D007677:Kidney Function Tests; D007683:Kidney Tubular Necrosis, Acute / Q000188:drug therapy* / Q000473:pathology* / Q000517:prevention & control; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011336:Probability; D011758:Pyrroles / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism
D016166:Free Radical Scavengers; D005839:Gentamicins; D006538:Heptanoic Acids; D016328:NF-kappa B; D011758:Pyrroles; D009569:Nitric Oxide; D000069059:Atorvastatin; D048051:p38 Mitogen-Activated Protein Kinases