Abrogation of cisplatin-induced nephrotoxicity in rats by Berne date extract through ameliorating oxidative stress, inflammation and apoptosis El-Sayed M. El-Sayed 1* , Ahmed M. Mansour 1 , and Mohamad Y. Ghobara 1 1 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt *E-mail: elsayed200_1956@hotmail.com Telephone: +201117154140 Abstract Our study aimed to investigate the possible protective effect of Berne date extract on cisplatin-induced nephrotoxicity. A single dose of cisplatin (6 mg/kg) was given intraperitoneally (i.p) to male rats produced significant elevation in serum urea, creatinine and TNF-α levels with significant reduction in serum albumin. It also increased kidney contents of lipid peroxides measured as malondialdehyde (MDA) and caspase-3 contents accompanied by a significant decrease in kidney contents of reduced glutathione (GSH) as well as enzymatic activities of catalase (CAT) and superoxide dismutase (SOD) compared to that of the control group. On the other hand, administrations of Berne date extract and vitamin E (a standard reference antioxidant drug) given per os (p.o) in doses of 300 mg/kg and 1g/kg, respectively for 14 days before cisplatin and 7 consecutive days after cisplatin injection ameliorated the cisplatin-induced nephrotoxicity as indicated by the restoration of kidney function and oxidative stress parameters. Furthermore, they reduced the histopathological changes induced by cisplatin. In conclusion, Berne date extract showed protective effect against cisplatin-induced nephrotoxicity; effects that may be attributed to antioxidant, anti-inflammatory and antiapoptotic activities. KEYWORDS: Antioxidant; Caspase-3; Cisplatin; Berne date extract. Introduction Cisplatin is still used as a fist-line chemotherapeutic agent for solid tumors such as nasopharyngeal cancer, lung cancer and ovarian cancer [1]. However, cisplatin has severe side effects such as gastrointestinal toxicity, bone marrow suppression, ototoxicity, neuropathy and nephrotoxicity. Nephrotoxicity is the major side effect that may restrict the therapeutic use of cisplatin [2-4]. The most severe nephrotoxicity of cisplatin is acute kidney injury, occurring in 20-30% of patients treated with cisplatin [5]. Nephrotoxicity is found in 28-36% patients who received a single dose (50 mg/m 2 ) of cisplatin [6]. In addition to direct tubular toxicity, cisplatin induces two models of cell death: apoptosis and necrosis. Necrosis has been mainly associated with high doses of cisplatin, whereas apoptosis is associated with therapeutic doses [7]. Also, inflammation has been implicated in the pathogenesis of cisplatin-induced nephrotoxicity [8]. Several studies have also reported that cisplatin-induced oxidative stress is involved in the development of renal tubule injury [3, 9]. The involvement of oxidative stress was further supported by the fact that free radical scavengers and antioxidants prevent cisplatin -induced nephrotoxicity [10, 11]. Because of the importance of cisplatin, many studies have focused on protective strategies targeting the cisplatin-induced nephrotoxicity. Hydration was developed to reduce the cisplatin-induced nephrotoxicity, however many hydration protocols for cisplatin are available; some components such as duration and volume of hydration remain controversial. Also, there is no standard regimen for cisplatin hydration [2, 12, 13]. Many antioxidant agents were investigated for their preventive abilities against cisplatin-induced nephrotoxicity. Some researches recommended the use of enriched diets with natural antioxidants like methionine, vitamin E and ascorbic acid [14, 15]. Others reported that the use of sulfhydryl-containing drugs, such as N-acetylcysteine, captopril, sodium thiosulfate and lipoic acid, could also exert antioxidant activity [16, 17]. The fruit of the date palm (Pheonix dactylifera L.) is an important commercial crop in many countries of Middle East. Dates are a good source of energy, vitamins, and elements [18]. Besides nutritional value, date fruits are rich in phenolic compounds possessing antioxidant activity. Several studies have reported such activity of date fruits from several countries [19-25]. These studies showed that fresh and dried dates varied quantitatively and qualitatively in their phenolic acids content. The antioxidant activity is attributed to the wide range of phenolic compounds in dates including ferulic, p-coumaric and sinapic acids, flavonoids and procyanidins [21-28]. El-Sayed M. El-Sayed et al./ International Journal of Pharma Sciences and Research (IJPSR) ISSN : 0975-9492 Vol 6 No 9 Sep 2015 1226