Biotechnol. Appl. Biochem. (2009) 52, 227–232 (Printed in Great Britain) doi:10.1042/BA20080086 227 Renal oxidative stress and nitric oxide production in streptozotocin-induced diabetic nephropathy in rats: the possible modulatory effects of garlic (Allium sativum L.) Amr D. Mariee* 1 , Gamil M. Abd-Allah* and Mohamad F. El-Yamany† *Biochemistry Department, College of Pharmacy, Al-Azhar University, Cairo, Egypt, and †Pharmacology Department, College of Pharmacy, Cairo University, Cairo, Egypt The purpose of the present study was to investig- ate the effects of garlic (Allium sativum L.) on the dia- betic nephropathy and oxidative stress induced by STZ (streptozotocin) in rats. Diabetes was induced in Male Sprague–Dawley rats by administering a single intraperitoneal injection of STZ (60 mg/kg of body weight). Administration of garlic, prepared as FGH (fresh garlic homogenate) significantly attenuated STZ-induced diabetic nephropathy as evaluated by assessment of serum glucose, insulin, total TAG (tri- acylglycerol), TC (total cholesterol) and Ccr (creatinine clearance) in control and STZ-induced diabetic rats. Urinary excretions of albumin and NAG (N-acetyl-β - D-glucosaminidase) were also reduced following the treatment with FGH. In addition, significant inhibition of TBARSs (thiobarbituric acid-reacting substances) with a marked improvement of GSH content in the kidney homogenates was also observed. Moreover, renal tissue content and urinary excretion of nitrites were markedly decreased in this model, and virtually enhanced to the same levels as in the non-diabetic kidney following FGH supplementation. These data revealed that FGH has the ability to ameliorate STZ- induced diabetic nephropathy possibly through parti- cipation in the inhibition of oxidative damage to kidney and/or increased kidney nitric oxide bioavailability. Introduction Diabetic nephropathy is one of the major late complications of diabetes mellitus, which occurs in 40 % of human diabetic cases [1]. Oxidative stress is regarded as an important factor in the initiation and development of diabetic complications [2,3]. Moreover, Honing et al. [4] reported that endogenous NO (nitric oxide) synthesis is diminished in diabetes and referred this impairment to the reduced availability of L-arginine, a precursor of NO, and increased consumption of NADPH, an essential co-factor for NOS (nitric oxide synthase) activity. Furthermore, excessive ROS (reactive oxygen species) and oxidative stress, which characterize prolonged hyperglycaemia. are found to be associated with subsequent NO breakdown [5]. STZ (streptozotocin), derived from a fermentation broth of Streptomyces achromogenes, was first isolated as a new antibiotic in 1956 and showed a significant antimicrobial action for a wide spectrum of organisms [6]. Studies of mur- ine tumours led to the discovery that STZ produced hyper- glycaemia, and further toxicology studies in dogs and rhesus monkeys demonstrated that STZ had a potent diabetogenic effect [7,8]. Ever since, STZ has been used as a diabeto- genic agent in experimental animals. Garlic (Allium sativum L., Liliaceae) is one of the most popular flavouring agents used worldwide. Garlic is stated to possess biologically active compounds which exert multi- ple therapeutic benefits that have been well established by epidemiological studies and animal experiments [9,10]. Garlic has also been reported to reduce free-radical- induced oxidative damage in experimental models and in humans [11,12]. Nevertheless, the therapeutic properties of garlic have only a little scientific support and have not yet been definitely explained. Garlic’s strong odour is largely due to sulfur-containing compounds, which are believed to account for most of its medicinal properties [13,14]. However, the lack of this characteristic smell in most of the pharmaceutically active preparations obtained from garlic brings the efficacy of those preparations into question [15]. Different trials to preserve the renal functions that have declined owing to prolonged hyperglycaemia have been car- ried out by various research groups [1,5,16,17]. Accordingly, in the present study, we have conducted a model of diabetic nephropathy in rats induced by STZ, to investigate the Key words: diabetes, garlic, nephropathy, nitric oxide, oxidative stress, streptozotocin. Abbreviations used: Ccr, creatinine clearance; FGH, fresh garlic homogenate; NAG, N-acetyl-β-D-glucosaminidase; NOS, nitric oxide synthase; ROS, reactive oxygen species; STZ, streptozotocin; TAG, triacylglycerol; TBARS, thiobarbituric acid-reacting substance; TC, total cholesterol. 1 To whom correspondence should be addressed (email amrmariee@yahoo.co.uk). C  2009 Portland Press Ltd