Original Article EFFECT OF THE JOINT SUPPLEMENTATION OF VITAMIN C AND VITAMIN E ON NICKEL HEAMATOTOXICITY AND NEPHROTOXICITY IN MALE SWISS ALBINO MICE FAOUZI DAHDOUH 1 , SALAH ATTALAH 2 , MOHAMED REDA DJABAR 1 , ZINE KECHRID 3 1 Laboratory of Toxicology, Department of Biology, Faculty of Sciences, Badji Mokhtar University, Annaba, Algeria, 2 Department of Animal Biology, Ethnobotany Palynology and Ethnopharmacology- Toxicology Laboratory; Faculty of Natural Science and Life, Montouri University Constantine, Algeria, 3 Laboratory of Biochemistry and Applied Microbiology, Department of Biochemistry, Badji Mokhtar University, Annaba, Algeria. Email: kechridzine@yahoo.fr Received: 28 Feb 2016 Revised and Accepted: 20 Apr 2016 ABSTRACT Objective: The aim of this study was to investigate the effect of vitamins C and E separately and in combination against nickel-induced alterations in haematological indices and kidney dysfunction. Methods: Male Swiss albino mice were divided into eight equal groups: Control, vitamin C (Vit C), vitamin E (Vit E), vitamin C and vitamin E (Vit C+Vit E), nickel (Ni), nickel and vitamin C (Ni+Vit C), nickel and vitamin E (Ni+Vit E), and nickel plus vitamins C and E (Ni+Vit C+Vit E). Vitamin C (1g/l) was given to mice through their drinking water. Vitamin E (1g/kg) and nickel as nickel sulfate (2.7 mg/kg) were supplemented in diet for four weeks. Results: Nickel caused a significant decrease in body weight, food and water consumption along with significant increase in the absolute and relative kidney weights. Haemoglobin, red blood cells count (RBC), hemoglobin (Hb) concentration, platelet counts (Plt) and packed cell volume (PCV) were significantly diminished, while white blood cells count (WBC) increased in nickel exposed mice. The renal damage induced by nickel was evidenced by a significant increase in the levels of serum urea, creatinine and uric acid. However, vitamins C and E in combination more significantly ameliorated the altered histopathological and biochemical changes in the kidney as well as hematological parameters of Ni intoxicated mice than either vitamin C or E. Conclusion: The study showed that vitamin C and E combination effectively attenuated Ni-induced heamatotoxicity and nephrotoxiicty in mice. Keywords: Nickel, Vitamins C, Vitamin E, Heamatotoxicity, Kidney injury, Histopathology © 2016 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) INTRODUCTION Nickel is a toxic metal that released into the environment by industrial activities, such as the production of batteries and paints, and also a by-product of metal alloys and medical implants. Thus nickel is an important material in industries, and hence, public health environmental problems become inevitable following exposure to nickel compounds via contaminated water and foodstuffs [1, 2]. Nickel cannot be metabolized and, therefore, accumulates in the body, where it can accumulate to high levels in certain organs, in particular, the liver and the kidney, leading to serious health effects [3]. The kidney is particularly predisposed to nickel-induced toxicity and carcinogenicity due to its involvement in nickel toxicokinetics and excretion through urine, as well as it serves as a major organ of Ni accumulation [4]. Several reports are available showing that nickel-induced nephrotoxicity is strongly related with histopathological and serum biochemistry alterations [5, 6]. Moreover, nickel is a known cytotoxic metal that induces kidney cell damages [7, 8]. Although the toxic mechanisms of nickel toxicity and carcinogenicity are still poorly understood. On the other hand, severe adverse heamtotoxic effects including disorders of the bone marrow, haematopoietic systems and the onset of anemia have been noticed in Ni exposed animals [9, 10]. The hematotoxic effect of nickel is basically due to over stimulation of metallothionein and subsequent inducing production of reactive oxygen species (ROS) that leads to oxidative damage in erythrocytes [11, 12]. Recently, the exogenous supplementation of antioxidant molecules such as vitamins C and E have received a wide attention due to their ability to quench reactive oxygen species (ROS) and thereby protecting cellular damage [13]. Vitamin E (dl-α-tocopherol) known as a lipid soluble antioxidant, improves antioxidant defense, prevents lipid peroxidation chain reactions and it can scavenge molecular oxygen, peroxide and hydroxyl radicals and atomic oxygen radicals [14],while vitamin C (ascorbic acid) is known as a potent antioxidant, belongs to the water soluble class of vitamins. Vitamin C has the ability to scavenge molecular oxygen and hydroxyl radicals and atomic oxygen radicals [15]. Numerous research workers have studied the beneficial effect of vitamin C or vitamin E against nickel toxicity following in vivo animal studies [16, 17] and in vitro studies [18] over the last few years. To our knowledge, this was the first study on the protective effect of vitamins C and E combination against nickel-induced nephrotoxicity and haematotoxicity in mice. MATERIALS AND METHODS Animals Sixty-four male Swiss albino mice weighing 29–33 g (Animal Unit of “Pasteur” Algiers Institute, Algeria) were used in this study. Animals were housed in plastic cages under a light-dark cycle 12/12 hour, a temperature 22±2 °C and humidity 40% with ad-libitum access to food and water. All experiments were carried out in accordance with ethical approval (AFRO. 123, 2009). Unless otherwise noted, all chemicals were obtained from Sigma Chemical Company (St Louis, France). Experimental design Mice were randomly divided into eight groups of eight mice each and subjected to various daily treatment regimes: Group I: (Control mice) animals fed a standard diet and given bidistilled drinking water. GroupII (Vit C): Mice received a standard diet and vitamin C in bidistilled drinking water (1g/l). Group III (Vit E): Animals received standard diet enriched with vitamin E (1g/kg of diet). Group IV (Vit C+Vit E): Mice received vitamin E (1g/kg of diet) and vitamin C (1g/l of bidistilled drinking water). Group V (Ni): Mice received standard diet supplemented with nickel sulfate (2,7g NiSO4/kg diet). International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 8, Issue 6, 2016