Experimental and Toxicologic Pathology 65 (2013) 327–334 Contents lists available at SciVerse ScienceDirect Experimental and Toxicologic Pathology jo u rn al h omepage: www.elsevier.de/etp Amelioration of CCl 4 -induced nephrotoxicity by Oxalis corniculata in rat Muhammad Rashid Khan ∗ , Hina Zehra Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 4400, Pakistan a r t i c l e i n f o Article history: Received 4 October 2010 Accepted 29 November 2011 Keywords: Oxalis corniculata Carbon tetrachloride Nephrotoxicity Oxidative stress Lipid peroxidation a b s t r a c t CCl 4 induces oxidative stress in various tissues by altering antioxidant enzymes defense system. In this study we investigated the chemical composition and protective role of Oxalis corniculata methanol extract (OCME) on CCl 4 -induced nephrotoxicity in rat. Presence of flavonoids, alkaloids, terpenoids, saponins, cardiac glycosides, phlobatannins and steroids was determined in OCME while tannins were absent. Total phenolic contents estimated were 7.76 ± 0.36 (mg gallic acid equivalents/g extract) while total flavonoid contents recorded were 6.92 ± 0.52 (mg rutin equivalents/g extract). Intraperitoneal injection of CCl 4 (1 ml/kg b.w., 20% in olive oil) once a day for seven days caused nephrotoxicity as evident by ele- vated levels of urinary specific gravity, RBCs, WBCs, creatinine, protein, urobilinogen and nitrite. Serum level of creatinine, urea, blood urea nitrogen were significantly increased while protein and creatinine clearance was decreased by CCl 4 treatment in kidney samples. Activity of antioxidant enzymes; cata- lase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and glutathione concentration was decreased whereas lipid peroxidation and protein contents were increased along with histopathological injuries. Treatment with OCME caused significant recovery in changed parameters. It could be concluded that OCME has a protective role against CCl 4 -induced oxidative stress in rat, due to antioxidant effects of phenolics. © 2011 Elsevier GmbH. All rights reserved. 1. Introduction Oxidative stress is commonly defined as an imbalance between oxidants and reductants (antioxidants) at the cellular or individual level and cause oxidative modification of cellular macromolecules, cell death by apoptosis or necrosis, as well as structural tissue damage (de Diego-Otero et al., 2009). Most free radicals in biolog- ical systems are derivatives of oxygen (“Reactive Oxygen Species”, ROS), but there are also derivatives of nitrogen (“Reactive Nitro- gen Species”, RNS). Various exogenous sources of ROS (ionizing and non-ionizing radiation, toxic gases, chemicals and toxins) also con- tribute directly or indirectly to the total oxidant load. The cellular macromolecules, in particular DNA, proteins and lipids, are natu- ral targets of oxidation. Numerous oxidative modifications to DNA have been characterized, which can lead to base misincorporations, mutations, single or double DNA strand breaks and eventually cell death (Poulsen, 2005). Carbon tetrachloride (CCl 4 ) is known to induce ROS, deplete antioxidant defenses; enzymes and substrates to cause oxidative stress in different tissues. CCl 4 in its first step of biotransforma- tion is catalyzed by cytochrome P450 enzymes (mainly CYP2E1), in to highly reactive trichloromethyl radical ( • CCl 3 ), which, in the ∗ Corresponding author. Tel.: +92 51 90643086; fax: +92 51 9205753. E-mail address: mrkhanqau@yahoo.com (M.R. Khan). presence of oxygen, is subsequently converted in to even more reactive trichloromethylperoxyl radical ( • OOCCl 3 ) and initiate the process of lipid peroxidation (Halliwell and Gutteridge, 2007). The use of certain antioxidants such as vitamin C and E may help to decrease the toxicity of chemical toxins. Recently, plant extracts rich in polyphenolics have also been used as antioxidants (Khan et al., 2010a). Oxalis corniculata is rich in niacin, vitamin C and -carotene. The juice of the plant, mixed with butter, is applied to muscu- lar swellings, boils and pimples (Manandhar, 2002). It is used as complementary medicine in wound healing, anemia, dys- pepsia, cancer, piles, dementia and convulsions (Taranalli et al., 2004; Madhavachetty et al., 2008). Other alternative uses are; anthelmintic, anti-inflammatory, astringent, depurative, diuretic, emmenagogue, febrifuge, lithontripic, stomachic and styptic. It is also used in the treatment of influenza, fever, urinary tract infec- tions, enteritis, diarrhea, traumatic injuries and sprains (Chopra et al., 1986). O. corniculata is also used as antiseptic, refrigerant, diaphoretic, diuretic and anti-diabetic. The juice of the plant is given in stomach troubles and in jaundice as well (Hussain et al., 2008). How- ever its antioxidant effects had not been tested in animals. The aim of the present investigation was to evaluate the protective effects of OCME on the urinary and serum biomarkers, histopathol- ogy and oxidative stress induced by CCl 4 in Sprague-Dawley rats. 0940-2993/$ – see front matter © 2011 Elsevier GmbH. All rights reserved. doi:10.1016/j.etp.2011.11.007