Pak. J. Pharm. Sci., Vol.22, No.4, October 2009, pp.373-380 373 L-ARGININE AUGMENTS THE ANTIOXIDANT EFFECT OF GARLIC AGAINST ACETIC ACID -INDUCED ULCERATIVE COLITIS IN RATS GAMAL ELDIN I. HARISA 1 , OSAMA M. ABO-SALEM 2 , EL-SAYED M. EL-SAYED 3*, EHAB I. TAHA 4 AND NERMIN EL-HALAWANY 5 1 Biochemistry Department, 2&3 Pharmacology and Toxicology Department & 4 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy (boys), Al-Azhar University, Nasr City, Cairo, Egypt 5 Department of Cell Biology, National Research Center, Dokki, Giza, Egypt ABSTRACT Garlic contains many sulfhydryl compounds that act as antioxidants. However, the role of nitric oxide (NO) in inflammation is controversial. The aim of the present study is to investigate the possible protective effect of garlic against acetic acid-induced ulcerative colitis in rats, as well as the probable modulatory effect of L- arginine (NO precursor) on garlic activity. Intra-rectal inoculation of rats with 4% acetic acid for 3 consecutive days caused a significant increase in the colon weight and marked decrease in the colon length. In addition, acetic acid induced a significant increase in serum levels of nitrate as well as colonic tissue content of malondialdehyde (MDA). Moreover, colonic tissue contents of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were markedly reduced. On the other hand, pre-treatment of rats with garlic (0.25g/kgbwt, orally) for 4 consecutive weeks and 3days during induction of colitis significantly reduced the increase in the colon weight induced by acetic acid and ameliorated alterations in oxidant and antioxidant parameters. Interestingly, oral co-administration of garlic (0.25g/kgbwt) and L-arginine (625mg/kgbwt) for the same period of garlic administration mitigated the changes in both colon weight and length induced by acetic acid and increased garlic effect on colon tissue contents of MDA and GSH. In conclusion, L-arginine can augment the protective effect of garlic against ulcerative colitis; an effect that might be mainly attributed to its NO donating property resulting in enhancement of garlic antioxidant effect. Further studies will be needed to determine which one of the active ingredients of garlic has the main antioxidant effect to be used with L-arginine. Keywords: Garlic; L-arginine; colitis, antioxidant. INTRODUCTION Ulcerative colitis is a chronic inflammatory disease of the colon and rectum. The exact cause remains unknown. Possible etiological factors, including genetic, immunological, reactive oxygen species (ROS) and environmental factors have been implicated (Kirsner and Shorter, 1982; Jewell and Patel, 1985; Millar et al., 1996). The main sources of ROS in the inflammed mucosa are activated leukocytes and neutrophils which are capable of producing superoxide and cascade of various reactive species leading to the formation of reactive hydroxyl radicals and peroxides. These products cause impairment in cell membrane function via lipid peroxidation in inflammatory bowel disease. Those intermediate products of oxygen metabolism (superoxide, hydroxyl radicals and H 2 O 2 ) are controlled by various cellular enzymes including superoxide dismutase (SOD), catalase (CAT) and non-enzymes as reduced glutathione (GSH) (Buffinton and Doe, 1995; Furrie et al., 2004). There is substantial evidence for the involvement of oxidative stress and profound alterations in the biosynthesis of the labile free radical nitric oxide ( . NO) from L-arginine in the pathogenesis of colitis (Myers et al., 1997; Aguilar-Nascimento et al., 1999; Barbosa et al., 2003; La et al., 2003). . NO is believed to participate in the regulation of the oxidation/reduction potential of various cells and may be involved in either the protection against or the induction of oxidative stress within various tissues depending on its concentration. Emerging evidence suggests that some diseases are related to either an inadequate or excessive production of . NO (Moncada and Higgs, 1993). The use of medicinal plants or their active components has become an increasingly attractive approach for the treatment of ulcerative colitis.Garlic as an antioxidant, has shown an inhibitory effect on lipid peroxidation and can enhance induction of endogenous antioxidants in rat kidney and liver (Banerjee et al., 2001; Khanum et al., 2004). Hence, this work was designed to study the possible protective effect of garlic against ulcerative colitis induced by acetic acid in rats, as well as the probable modulatory effect of L-arginine (NO precursor) on garlic activity. *Corresponding author: e-mail: elsayed200_1956@yahoo.com