Effect of Ellagic Acid, Cilostazol and Their Combination on Amikacin Induced Nephrotoxicity in Rats
Abstract Amikacin(AK) has the largest spectrum of aminoglycosides. However, its use is limited due to nephrotoxicity and ototoxicity. Ellagic acid (EA) is a plant phenolic structure. it has antioxidant, anticarcinogenic and antimutagenic properities. Cilostazol (CTZ) is a PDE Ш inhibitor, it is a potent vasodilator and antiplatelet drug. This study aimed to determine if EA and cilostazol have a protective effect against nephrotoxicity caused AK. Forty nine rats were divided into seven equal groups: control normal; AK 400mg/kg; EA 10 mg/kg; CTZ 10mg/kg; AK 400mg/kg plus EA 10mg/kg; AK 400mg/kg plus CTZ 10mg/kg; AK 400mg/kg plus EA 10mg/kg and CTZ 10mg/kg. For seven days, Drugs were given orally one hour before intramuscular injection of AK. After twenty-four hours from the last dosage, samples of blood were obtained to determine blood urea nitrogen (BUN) and creatinine levels in serum, kidneys were extracted and longitudinally divided into two parts, part for measuring the following parameters: malondialdehyde (MDA), catalase (CAT), reduced glutathione (GSH), interleukin 6 (IL6), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNFα), nuclear factor kappa B (NFκB) and Bcl-2 associated x protein (Bax), the other part was placed in formaldehyde solution and examined under light microscopy for routine histopathologic examination. The results of the present study proved that EA, CTZ and their combination protected rats against AK - induced nephrotoxicity; This effect might be a result of the antioxidant, anti-inflammatory and anti-apoptotic properties of these compounds.
