Original Article CLOVE OR GREEN TEA ADMINISTRATION ANTAGONIZES KHAT HEPATOTOXICITY IN RATS ENTSAR A. SAAD* 1 , EL-SHAHAT A. TOSON 1 , GALAL M. AHMED 1 1 Received: 20 Feb 2015 Revised and Accepted: 18 Mar 2015 Chemistry Department, Faculty of Science, Damietta University, Damietta, Egypt Email: entsarsaad@gmail.com ABSTRACT Objective: Khat consumption has become a common problem that affects the health aspects of life in Yemen and other parts in the world. The liver has been suspected to be particularly vulnerable to the harmful effects of khat use and until now khat hepatotoxicity effects are still controversial. This study was conducted to investigate the hepatoprotective effects of aqueous extracts of clove and green tea, as medicinal herbs with established antioxidant properties, against controversial hepatotoxicity effects of khat in rats. Methods: Rats received a daily oral dose of khat extract alone or in combination with green tea or clove extract for six weeks. To study the effects on liver cells, histopathology, routine liver function tests, malondialdehyde (MDA), total antioxidant capacity (TAC) and the activities of superoxide dismutase (SOD) and catalase (CAT) enzymes were investigated. Results: Khat administration showed marked liver injury; congestion in the portal vein with fibrous tissue proliferation, extended from the portal area and forming intralobular Porto-portal bridging fibrous septae. Besides significant routine liver function tests alterations, lipid peroxides elevation, and TAC reduction with significant inhibition of SOD and CAT activities. Conclusion: Combined administration of khat with clove or green tea protected hepatocytes via oxidative stress inhibition. They significantly counteracted the alterations in liver function tests, decreased lipid peroxidation and restored the antioxidant status to near normal levels. These results confirm khat hepatotoxicity and suggest that clove or green tea administration has strong hepatoprotective effects against khat induced hepatotoxicity in rats via antioxidant mediated mechanism. Keywords: Khat, Medicinal herbs, Hepatotoxic, Hepatoprotective. INTRODUCTION Khat (Catha edulis Forsk) is a shrub or small to medium sized evergreen tree that belongs to the Celastraceae family [1]. It is cultivated mainly in Yemen and East African Countries [2]. Its young shoots and leaves are chewed daily by over 20 000 000 people in these countries [3]. Khat spreads to other countries where East African communities are living [4]. Although there are more than 200 identified compounds in khat leaves, the phenylpropylamino alkaloids are primarily considered to be the addictive and reinforcing agents responsible for the continued chewing behavior [5]. The WHO reported that khat consumption has become a common problem that affects the health aspects of life [6]. Consumption of crude khat extract has been shown to produce oxidative stress in rats by altering activities of serum antioxidant enzymes [7]. The liver has been suspected to be particularly vulnerable to the harmful effects of khat use [8]. Some studies showed significant alterations in the hepatic biochemical and histological parameters throughout short-and long-term studies on khat toxicity [9] while other studies reported that there are no significant hepatic changes [10]. Liver function tests (LFTs) are commonly used to screen for liver disease, monitor the progression of known disease, and monitor the effects of potentially hepatotoxic drugs [11]. Increased levels of AST and ALT are an indicator of cellular infiltration and functional disturbance of the liver cell membranes [12]. ALP is a membrane bound and its alteration is likely to affect the membrane permeability and produce derangement in the transport of metabolites [13]. On the other hand, bilirubin and albumin values are associated with the secretory and synthetic functions of hepatic cells [14]. In the last few years there has been an exponential growth in the field of herbal medicine and these drugs are gaining popularity because of their natural origin and less side effects [15]. Currently diverse natural products have been evaluated for their hepatoprotective capacity in different models of hepatotoxicity [16- 19]. Syzygium aromaticum (clove) and Camellia sinensis (green tea) plants are commonly used traditionally in folk medicine and currently used as beverages by Egyptians. Clove flowers are also eaten in Egypt and some other countries [20]. Green tea extract contains polyphenols, tannin and caffeine. Its extract also includes pyroloquinoline quinone, a newly discovered vitamin [21]. Green tea catechins may reduce hepatic fibrosis by suppressing oxidative stress and controlling the transcription factor expression involved in stellate cell activation [22]. The antioxidant property of flavonoidal compounds of green tea extract contributes to decrease the hepatic oxidative stress and increase the levels of antioxidant enzymes [23]. Clove is one of the richest sources of phenolic compounds and possesses great potential for pharmaceutical, cosmetic, food and agricultural applications [24]. Since flavonoids are able to reduce xenobiotic-induced hepatotoxicity in animals and counteract the damaging effects of oxidative stress, cooperating with natural systems like endogenous protective antioxidant enzymes, clove shows antioxidant properties and its extracts could be used as food antioxidants [24, 25]. All of these encouraged us to estimate the probable SOD-like activity of clove and green tea aqueous extracts in vitro and to investigate their hepatoprotective effects as medicinal herbs with established antioxidant properties against both controversial pro oxidant and hepatotoxicity effects of khat in vivo. MATERIALS AND METHODS Plant materials Fresh khat leaves were harvested from private farm in Sana’a Governorate (Republic of Yemen). The leaves were washed, air dried, pulverized, stored in plastic bags and kept at 4 ˚C [26], then transported to Biochemistry Laboratory, Chemistry Department, Faculty of Science, Damietta University, Egypt. Clove dried flower buds and green tea dried leaves were purchased from the local market, Egypt. Preparation of plant extracts 100 g of dried khat leaves were soaked in 500 ml of distilled water for 24 h then heated for 30 min at 60 ˚C. The contents were filtered International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 7, Issue 6, 2015 Innovare Academic Sciences