CLOVE OR GREEN TEA ADMINISTRATION ANTAGONIZES KHAT HEPATOTOXICITY IN RATS
Keywords:Khat, Medicinal herbs, Hepatotoxic, Hepatoprotective
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.
Shewamene Z, Engidawork E. Subacute administration of crude khat (Catha edulis F.) extract induces mild to moderate nephrotoxicity in rats. BMC Complement Altern Med 2014;14:66.
Patel NB. Mechanism of action of cathinone: the active ingredient of khat (Catha edulis). East Afr Med J 2000;77:329â€“32.
Riyaz S, Imran M, Gleeson D, Karajeh MA. Khat (Catha Edulis) as a possible cause of autoimmune hepatitis. World J Hepatol 2014;6(3):150-4.
Masoud A, Al-Assar A, Abu-zeed H. Chewing Catha Edulis with amphetamine-like effect alters liver and kidney functions of female chewers. IJPSI 2014;3(2):34-9.
Feyissa AM, Kelly JP. A review of the neuropharmacological properties of khat. Prog Neuro-Psycho pharmacol Biol Psychiatry 2008;32:1147-66.
Kassim S, Islam S, Croucher R. Validity and reliability of a Severity of Dependence Scale for khat (SDS-khat). J Ethnopharmacol 2010;132(3):570â€“7.
Al-Qirim TM, Shahwan M, Zaidi KR, Uddin Q, Banu N. Effect of khat, its constituents and restraint stress on free radical metabolism of rats. J Ethnopharmacol 2002;83(3):245-50.
Cox G, Rampes H. Adverse effects of khat: a review. Adv Psychiatr Treat 2003;9:456-63.
Al-Habori M, Al-Aghbari A, Al-Mamary M, Baker M. Toxicological evaluation of Catha edulis leaves: a long term feeding experiment in animals. J Ethnopharmacol 2002;83(3): 209-17.
Al-Zubairi A, Ismail P, Pei CP, Rhmat A. Genotoxic effect of Catha edulis (khat) crude extract after sub-chronic administration in rats. Environ Toxicol Pharmacol 2008;25(3):298-303.
Abolfathi AA, Mohajeri D, Rezaie A, Nazeri M. Protective effects of green tea extract against hepatic tissue Injury in Streptozotocin-Induced diabetic rats. eCAM 2012;2012:10.
Drotman R, Lawhorn G. Serum enzymes as indicators of chemically induced liver damage. Drug Chem Toxicol 1978;1(2):163â€“71.
Mehana EE, Meki AR, Fazili KM. Ameliorated effects of green tea extract on lead induced liver toxicity in rats. Exp Toxicol Pathol 2012;64(4):291â€“5.
Muriel P, Garciapina T, Perez-Alvarez V, Mourelle M. Silymarin protects against paracetamol-induced lipid peroxidation and liver damage. J Appl Toxicol 1992;12(6):439â€“42.
Grover JK, Yadav S, Vats V. Medicinal plants of India with antidiabetic potential. J Ethnopharmacol 2002;81:81â€“100.
Madkour FF, Abdel-Daim MM. Hepatoprotective and antioxidant activity of dunaliella salina in paracetamol-induced acute toxicity in rats. Indian J Pharm Sci 2013;75(6):642-8.
Abdel-Daim MM. Pharmacodynamic interaction of Spirulina platensis with erythromycin in Egyptian Baladi bucks (Capra hircus). Small Ruminant Res 2014;120(2):234-41.
Madrigal-SantillÃ¡n E, Madrigal-Bujaidar E, Ãlvarez-GonzÃ¡lez I, Sumaya-MartÃnez MT, GutiÃ©rrez-Salinas J, Bautista M, et al. Review of natural products with hepatoprotective effects. World J Gastroenterol 2014;20(40):14787â€“804.
Abdel-Daim MM, Ghazy EW. Effects of Nigella sativa oil and ascorbic acid against oxytetracycline-induced hepato-renal toxicity in rabbits. IJBMS 2015;18(3):221-7.
Saad EA, Habib SA. Effect of crude extracts of some medicinal plants on the osmotic stability of human erythrocytes in vitro. J Free Radicals Antioxidants 2013;139:265-72.
Kasahara T, Kato T. Nutritional biochemistry: A new redox-cofactor vitamin for mammals. Nature 2003;422(6934):832.
Kobayashi H, Tanaka Y, Asakawa T, Tanikawa K, Kage M, Minoru Y. The antioxidant effect of green tea catechin ameliorates experimental liver injury. Phytomed 2010;17(3-4):197-202.
Hasanein MA, Abdel Gawad SH, Abd El-Megeid AA. Effect of water extract prepared from green tea, Black tea and cinnamon on obese rats suffering from diabetes. WASJ 2012;20(7):976-87.
Diego FR, Claudia RF, Wanderley PO. Clove (Syzygium aromaticum): a precious spice. Asian Pac J Trop Biomed 2014;4(2):90-6.
Kadarian C, Broussalis AM, MiÃ±o J, Lopez P, Gorzalczany S, Ferraro G, et al. Hepatoprotective activity of Achyrocline satureioides (Lam) DC. Pharm Res 2002;45(1):57-61.
Al-Medhar AA, El-Denshary ES, Abdel-Wahab M. Alpha lipoic acid and alpha-tocopherol counteract the oxidative stress and liver damage in rats sub-chronically treated with khat (Catha edulis) extract. GJP 2012;6(2):94-105.
Kalix P. Khat, an amphetamine-like stimulant. J Psychoact Drugs 1994;26(1):69-74.
Abozid MM, El-Syed SM. Antioxidant and protective effect of clove extracts and clove essential oil on hydrogen peroxide treated rats. Int J Chem Tech Res 2013;5(4):1477-85.
NIH [National Institutes of Health]. Guide for the care and use of laboratory animals. 7th ed. Washington, DC: National Academy Press; 1996.
Chapman MH, Kajihara M, Borges G, O'Beirne J, Patch D, Dhillon AP, et al. Severe, acute liver injury and khat leaves. N Engl J Med 2010;362:1642-4.
Widler P, Mathys K, Brenneisen R, Kalix P, Fisch H. Pharmacodynamics and pharmacokinetics of khat: a controlled study. Clin Pharmacol Ther 1994;55(5):556-62.
Kalix P. Pharmacological properties of the stimulant khat. Pharmacol Ther 1990;48(3):397-416.
Guyton AC, Hall JE. The liver as an organ. In: Guyton and Hall textbook of medical physiology. Philadelphia: Saunders/Elsevier; 2011. p. 837-42.
Targher G, Day CP. Liver enzymes, nonalcoholic fatty liver disease and incident cardiovascular disease. Hepatol 2011;53(1):375.
Thapa BR, Walia A. Liver function tests and their interpretation. Indian J Pediatr 2007;74(7):663-71.
Al-Zubairi AS, Ismail P, Pei Pei C, Wahab
SIA, Rahmat A. Biochemical effects of sub-chronic administration of Catha edulis (Khat) crude extract in rats. Res J Pharmacol 2007;1(4):84-90.
Kalix P. Catha edulis, a plant that has amphetamine effects. Pharm World Sci 1996;18(2):69-73.
Cullen JM. Mechanistic classification of liver injury. Toxicol Pathol 2005;33(1):6-8.
Schnee JM, Hsueh WA. Angiotensin II, adhesion, and cardiac fibrosis. Cardiovasc Res 2000;46(2):264-8.
Saad EA. Curative and protective effects of L-arginine on carbon tetrachloride-induced hepatotoxicity in mice. BBRC 2012;423(1):147-51.
Yin H, Xu L, Porter NA. Free radical lipid peroxidation: mechanisms and analysis. Chem Rev 2011;111(10):5944-72.
Al-Hashem FH, Bin-Jaliah I, Dallak MA, Nwoye LO, Al-Khateeb M, Sakr HF, et al. Khat (Catha edulis) extract increases oxidative stress parameters and impairs renal and hepatic functions in rats. BMB 2011;33(1):32-6.
Valko M, Leibfritz D, Moncol J, Cronin MTD, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007;39(1):44-84.
Ganga Rao B, Jaya raju N. Investigation of hepatoprotective activity of spondias PINNATA. IJPSR 2010;1(3):193-8.
Shekarforoush S, Aghababa H, Azizi M, Changizi-Ashtiyani S, Zarei A, Rezaei A, et al. A comparative study on the effects of glutathione and green tea extract (Camellia sinensis L) on thioacetamide-induced hepatotoxicity in male adult Wistar rats. Zahedan J Res Med Sci 2014;16(12):5-18.
Miyagawa C, Wu C, Kennedy DO. Protective effect of green tea extract and tea polyphenols against the cytotoxicity of 1, 4-naphthoquinone in isolated rat hepatocytes. Bio Sci Biotechnol Biochem 1997;61:1901-5.
Khorsandi LS, Javadnia F, Orazizadeh M, Abdolahi M. Effect of green tea (Camellia sinensis L.) extract on acetaminophen induced acute hepatotoxicity in mice. Persian Iran J Med Aromat Plants 2010;26(1):22-9.
Paquay B, Haenen GR, Stender G, Wiseman SA, Tijburg LBM, Bast A. Protection against nitric oxide toxicity by tea. J Agric Food Chem 2000;48:5768-72.
El-Beshbishy HA, Tork OM, El-Bab MF, Autifi MA. Antioxidant and antiapoptotic effects of green tea polyphenols against azathioprine-induced liver injury in rats. Pathophysiol 2011;18(2):125-35.
Sai K, Kai S, Umemura T, Tanimura A, Hasegawa R, Inoue T, et al. Protective effects of green tea on hepatotoxicity, oxidative DNA damage and cell proliferation in the rat liver induced by repeated oral administration of 2 nitropropane. Food Chem Toxicol 1998;36(12):1043-51.
Mehana EE, Meki AR, Fazili KM. Ameliorated effects of green tea extract on lead induced liver toxicity in rats. Exp Toxicol Pathol 2012;64(4):291-5.
Xu C, Shu WQ, Qiu ZQ, Chen JA, Zhao Q, Cao J. Protective effects of green tea polyphenols against subacute hepatotoxicity induced by mi-crocystin-LR in mice. Environ Toxicol Pharmacol 2007;24(2):140-8.
Ram P, Shakir A, Luqman AK. Hepatoprotective Effect of Syzygium aromaticum extract on acute liver injury induced by thioacetamide. Int J Pharm Clin Res 2010;2(2):68-71.