JJBS Volume 11, Number 5,December 2018 ISSN 1995-6673 Pages 517 - 525 Jordan Journal of Biological Sciences Mitigation of Alpha-Cypermethrin-Induced Hepatotoxicity in Rats by Tribulus terrestris Rich in Antioxidant Compounds Sami I. Ali 1* , Alaa A. Gaafar 1 , Amr A. Abdallah 2 , Sherien M. El-Daly 3 , Mona El- Bana 3 , and Jihan Hussein 3 1 Plant Biochemistry Department, National Research Centre, Dokki, Giza, Egypt. P.O. 12622, ID: 60014618. 2 Mammalian Toxicology Department, Central Agricultural Pesticides Lab, Agricultural Research Center, Ministry of Agriculture, Egypt. 3 Medical Biochemistry Department, National Research Centre, Dokki, Giza, Egypt. P.O. 12622, ID: 60014618. Received April 19 , 2018; Revised May 17, 2018; Accepted May 20, 2018 Abstract Tribulus terrestris is used traditionally as a medicinal herb to improve the sexual functions. However, its hepatoprotective effects against alpha-cypermethrin (an insecticide) hepatotoxic effects are still not fully elucidated. The present study investigates for the first time the hepatoprotective effect of the T. terrestris extract against alpha-cypermethrin induced liver toxicity in addition to its phytochemical composition and in vitro antioxidant activity. Several phenolic and flavonoids’ compounds (ellagic and ferulic acid, hesperidin and quercetrin) were screened in the T. terrestris extract by HPLC. The T. terrestris extract exhibited in vitro antioxidant activity using DPPH • , ABTS •+ , and reducing power assays. The remarkable effects of the T. terrestris extract in the attenuation of hepatotoxicity induced by α-cypermethrin in rats are investigated for the first time in the current study. The administration of the T. terrestris extract decreased liver enzymes; alanine amino transferase (ALT), and aspartate amino transferase (AST). Also, it increased antioxidant; glutathione (GSH) and paraoxnase- 1(POX-1) enzyme, and decreased oxidant; malondialdehyde (MDA) and nitric oxide (NO). Furthermore, it decreased liver inflammatory markers; tumor necrosis factor alpha (TNF - α), adiponectin and lipocalin. The hepatoprotective effect of T. terrestris extract could be attributed to its ability to hunt free radicals and induce the antioxidant enzymes expression in addition to the down-regulation of pro-inflammatory markers in liver injuries. Keywords: α-Cypermethrin, Hepatotoxicity, HPLC, Polyphenolic compounds, Tribulus terrestris. * Corresponding author. e-mail: samiali.nrc@gmail.com. 1. Introduction Pesticides are toxic chemicals, which contaminate the entire environment including air, soil, water, and have been detected in human and animal tissue samples all over the world (Carvalho, 2017). Prolonged exposure to toxic pesticides has shown harmful effect to the skin, eyes, liver, the gastrointestinal tract, kidneys, the reproductive system, nervous system, cardiovascular system, blood and the endocrine system (IPCS, 2010). Liver is the main target organ for drugs, xenobiotics, and other toxic chemicals because of the liver’s complex anatomical texture, different metabolic functions, and direct association with the gastrointestinal tract. Pesticides including cypermethrin are aggressive chemicals that cause liver damage including hepatic fibrosis, cirrhosis, steatosis and inflammation (Cataudella et al., 2012). Alpha Cypermethrin (α-CYP), a synthetic type II pyrethroid insecticide, is used extensively in different countries for pest control, because of its high influence against a wide range of insects and because of its low toxicity to mammals (Abdou et al., 2012). Despite the low toxicity of α-CYP, its accumulation in various food chains and persistence in different mammalian tissues including the liver, kidney, and the brain are the reasons behind its higher toxic levels (Yavasoglu et al., 2006; Singh et al., 2012). It induces mitochondrial dysfunction and oxidative stress especially lipid peroxidation in animal models, resulting in both an elevation of oxidative stress markers and a reduction in antioxidant activities (El-Demerdash, 2011). Moreover, Yavasoglu et al. (2006) reported that α- CYP treatment increased the apoptotic index in the liver of rats, and it might cause hazardous effects in different levels to non-target organisms. Several studies have reported that the pretreatment with different plant extracts as a source for natural antioxidants can alleviate the side effects and toxicity of cypermethrin in rats (Sushma and Devasena, 2010; Abdou et al., 2012). Tribulus terrestris L. is an annual flowering creeping plant that belongs to the family Zygophylaceae, which is native to the Mediterranean region. However, it grows widely in the warm regions of Africa, Asia, America, Europe, and Australia (Qureshi et al., 2014). It is known by different Arabic names: Ders El-Agouz, Hasak, Qutiba and Al-Gutub (Al-Ali et al., 2003), with some common names such as caltrop, goat head, puncture vine, bull’s head, devil’s thorn, and ground burr nut (Kostova and