HEPATO-PROTECTIVE ROLE OF THE AQUEOUS AND N-HEXANE EXTRACTS OF NIGELLA SATIVA LINN. IN EXPERIMENTAL LIVER DAMAGE IN RATS

Farida Yesmin; Zaida Rahman; Jesmin Fouzia Dewan; Asadul Mazid Helali; Nor Iza A Rahman; Ahmed G. Alattraqchi; Arefuddin Ahmed; Rabeya Yousuf; Abdus Salam; Mainul Haque

Authors

Farida Yesmin Gonoshashthaya Samajvittik Medical College (GSSVMC), Dhaka, Bangladesh
Zaida Rahman Enam Medical College & Hospital, Savar, Dhaka, Bangladesh
Jesmin Fouzia Dewan Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag Dhaka, Bangladesh
Asadul Mazid Helali Gonoshashthaya Samajvittik Medical College (GSSVMC), Dhaka, Bangladesh
Nor Iza A Rahman Universiti Sultan Zainal Abidin (UniSZA), Terengganu, Malaysia
Ahmed G. Alattraqchi Universiti Sultan Zainal Abidin (UniSZA), Terengganu, Malaysia
Arefuddin Ahmed Universiti Sains Malaysia, Malaysia
Rabeya Yousuf Universiti Kebangsaan Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia
Abdus Salam Universiti Kebangsaan Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia
Mainul Haque Universiti Sultan Zainal Abidin (UniSZA), Terengganu, Malaysia

Abstract

Objective: Liver disease is associated with the formation of oxygen derived free radicals. Reactive oxygen species (ROS) as well as nitrogen species are responsible for nuclear DNA fragmentation and cell death. Active principle of thymoquinone (TQ) of Nigella sativa acts as a scavenger of superoxide anion. Current study was conducted to evaluate the hepatoprotective effect of Nigella sativa on rats.

Methods: The study was carried out at prime postgraduate medical University of Bangladesh. Liver damage and oxidative stress were evaluated by measuring serum alanine amino transferase (ALT), hepatic malondialdehyde (MDA) and hepatic Glutathione (GSH) levels. Aqueous extract of Nigella sativa and n-hexane extract of Nigella sativa were administered orally into two groups' of rats through intra-gastric tube for 28 days. Both the groups received paracetamol intraperitoneally on day 28^th and were sacrificed on day 30^th. Subsequently, the following parameters were studied: Serum ALT, hepatic MDA, and hepatic GSH.

Results: Hepatic damage was evaluated by significant increases in serum ALT (p<0.001) and hepatic MDA (p<0.001) concentration with depleted hepatic GSH (p<0.001) in paracetamol treated group. Pre-treated with aqueous extract of Nigella sativa significantly reduced serum ALT (p<0.001) and hepatic MDA (p<0.001) levels and also significantly associated with the increase in hepatic GSH (p<0.01). Pretreatment with n-hexane extracts of Nigella sativa decreased serum ALT (p<0.001), hepatic MDA (p<0.001) and increased hepatic GSH (p<0.001).

Conclusion: Hepatoprotective properties of Nigella sativa in liver damage of experimental rats by reducing oxidative stress is evident. Protection afforded by the n-hexane extract of Nigella Sativa in pre-treated group has also been validated.

KEY WORDS: Hepatoprotective, Liver-damage, Nigella sativa Linn.

Downloads

Download data is not yet available.

Author Biographies

Farida Yesmin, Gonoshashthaya Samajvittik Medical College (GSSVMC), Dhaka, Bangladesh

Assistant Professor, Department of Pharmacology & Therapeutics

Zaida Rahman, Enam Medical College & Hospital, Savar, Dhaka, Bangladesh

Associate Professor, Department of Pharmacology & Therapeutics

Jesmin Fouzia Dewan, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag Dhaka, Bangladesh

Professor, Department of Pharmacology

Asadul Mazid Helali, Gonoshashthaya Samajvittik Medical College (GSSVMC), Dhaka, Bangladesh

Assistant Professor, Department of Pharmacology & Therapeutics

Nor Iza A Rahman, Universiti Sultan Zainal Abidin (UniSZA), Terengganu, Malaysia

Medical Lecturer, Faculty of Medicine and Health Sciences

Ahmed G. Alattraqchi, Universiti Sultan Zainal Abidin (UniSZA), Terengganu, Malaysia

Medical Lecturer, Faculty of Medicine and Health Sciences

Arefuddin Ahmed, Universiti Sains Malaysia, Malaysia

Senior Lecturer, Medical Radiation Programme School of Health Sciences

Rabeya Yousuf, Universiti Kebangsaan Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia

Medical Officer, Blood Bank Unit, Department of Pathology

Abdus Salam, Universiti Kebangsaan Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia

Associate Professor, Department of Medical Education

Mainul Haque, Universiti Sultan Zainal Abidin (UniSZA), Terengganu, Malaysia

Professor, Faculty of Medicine and Health Sciences

References

Hasan M, Khan AA. Development of gastroenterology in Bangladesh. J Gastroenterol Hepatol. 1997; 12: S13-S14.

Satyanarayana U, Chakrapani U. Biochemistry. 3rd ed. Calcutta: Books and Allied (P) Ltd; 2008.

Di-Luzio NR. A mechanism of the acute ethanol-induced fatty liver and the modification of liver injury by antioxidants. Lab Invest. 1966; 15: 50-63.

Fernandez-Checa JC, Kaplowitz N. Hepatic mitochondrial glutathione: transport and role in disease and toxicity. Toxicol App Pharmacol. 2005; 204: 263-73.

Harsha SN, Latha BV. In vitro antioxidant and in vitro anti-inflammatory activity of ruta graveolens methanol extract. Asian J Pharm Clin Res. 2011; 5(1): 32-35.

Kageyama F, Kobayashi Y, Kawasaki T, Toyokuni S, Uchida K, Nakamura H. Successful interferon therapy reverses enhanced hepatic iron accumulation and lipid peroxidation in chronic hepatitis C. Am J Gastroenterol. 2000; 95: 1041-50.

Wu J, Zern MA. Hepatic stellate cells: a target for the treatment of liver fibrosis. J Gastroenterol 2000; 35: 665-72.

Troll W, Wiesner R. The role of oxygen radicals as a possible mechanism of tumor promotion. Ann Rev Pharmacol Toxicol 1985; 25: 509-28.

Gerson RJ, Casini A, Gilfor D, Serroni A, Farber JL. Oxygen-mediated cell injury in the killing of cultured hepatocytes by acetaminophen. Biochem Biophys Res Commun 1985; 126: 1129-37.

Mitchell JR, Jollow DJ, Potter WZ, Gillette JR, Brodie BB. Acetaminophen-induced hepatic necrosis, I. Role of drug metabolism. J Pharmacol Exp Ther 1973; 187:185-94.

Prescott LF, Wright N, Roscoe P, Brown SS. Plasma paracetamol half-life and hepatic necrosis in patients with paracetamol overdose. Lancet 1971; 1: 519-22.

Lee WM. Acetaminophen and the U.S. acute liver failure study group: lowering the risks of hepatic failure. Hepatology 2004; 40: 6-9.

Jollow DJ, Mitchell JR, Potter WZ, Davis DC, Gillette JR, Brodie BB. Acetamimnophen-induced hepatic necrosis, II. Role of covalent binding in vivo. J Pharmacol Exp Ther 1973; 187: 195-02.

Brahams D. Paracetamol over dose: timing the antidote. Lancet 1989; 1: 567-68.

Lake BH, Harris RA, Phillips JC, Gangoli SD. Studies on the effects of l-ascorbic acid on acetaminophen-induced hepatotoxicity. Toxicol Appl Pharmacol 1981; 60: 229-40.

Krishnamoorthy P, Sangeetha M. Hepatoprotective effect of vitamin C on sodium nitrite-induced lipid peroxidation in albino rats. Indian J Biochem Biophys 2008; 45: 206-08.

Chowdhury M. Studies of the effects of Andrographis paniculata (Kalmegh) and cimetidine on paracetamol-induced hepatotoxicity. University of Dhaka: M.Phill thesis; 1991. p. 1-76.

Momtaz S. Study of the effect of Spirulina on serum GPT and Got levels of normal and paracetamol-induced hepatotoxic rats. University of Dhaka: M.Phill thesis; 1991.p. 1-67.

Khan MAL. Study of effect of l-ascorbic acid and Cajanus indicus (Arhar) on paracetamol-induced hapatotoxicity in rats. University of Dhaka: M.Phill thesis; 1991. p. 1-59.

Saha DR. Effects of Phyllanthus niruri on paracetamol-induced hepatotoxicity in rat. Bangabandhu Sheikh Mujib Medical University, Dhaka : M.Phill thesis; 1999. p. 1-74.

Iqbal JM. Evaluation of hepatoprotective potential of four different extract of Phyllanthus niruri on paracetamol-induced hepatotoxicity in rat. Bangabandhu Sheikh Mujib Medical University, Dhaka : M.Phill thesis; 2001. p. 1-87.

Chowdhury RT. Study of the hepatoprotective fraction (s) of Phyllanthus niruri Linn. (Bhuiamla) and their comparison with l-ascorbic acid in hepatotoxic rats. Bangabandhu Sheikh Mujib Medical University, Dhaka : M.Phill thesis; 2008. p. 1-82.

Khadr ME, Mahdy KA, El-Shamy KA, Morsy FA, El-Zayat SR, Abd-Allah AA. Antioxidant activity and hepatoprotective potential of black seed, honey and silymarin on experimental liver injuries induced by CCl4 in rats, J Applied Sci 2007; 7: 3909-17.

Martinez-Calva I, Campos-Apaez A, Rosales-Vega E, Mourelle M. Vitamin E improve membrane lipid alterations induced by CCl4 intoxication. J Appl Toxicol 1984; 4: 270-72.

Fraga CG, Arias RF, Llesuy SF, Koch OR, Boveris A. Effect of vitamin E and selenium deficiency on rat liver chemiluminescence. Biochem J 1987; 242: 383-86.

Nadkarni KM. Indian Materia Medica. 3rd ed. Bombay: Popular prakashan; 1976.

Haq A, Lobo PI, Al-Tufail M, Rama NR, Al-Sedairy ST. Immunomodulatory effect of Nigella sativa proteins fractionated by ion exchange chromatography. Int J Immunopharmacol. 1999; 21: 283-95.

Uddin N. Effects of Nigella sativa Linn (Kalajira) on serum glucose concentration in streptozotocin-induced diabetic rats. M.Phill thesis. Bangabandhu Sheikh Mujib Medical University: 2002. Bangabandhu Sheikh Mujib Medical University, Dhaka: M.Phill thesis; 2002. p. 1-72.

Khanam M. Effects of n-hexane extract of Nigella sativa Linn. (kalajira) upon serum glucose concentration of streptozotocin-induced diabetic rats. Bangabandhu Sheikh Mujib Medical University, Dhaka: M.Phill thesis; 2007. p. 1-68.

Ramadan MF, Morsed JT. Characterization of phospholipid composition of black cumin (Nigella sativa) seed oil. Nahrung/ Food 2002; 46: 240-44.

Hanafy MS, Hatem ME. Studies on the antimicrobial activity of Nigella sativa seed (black cumin). J Ethnopharmacol 1991; 34: 275-78.

Khan MAU, Ashfaq MK, Zuberi HS, Mahmood MS, Gilani AH. The in vivo antifungal activity of the aqueous extract from Nigella sativa seeds. Phytother Res 2003; 17: 183-186.

Akhtar MS, Riffat S. Field trial of saussurea lappa roots against nematodes and Nigella sativa seeds against cestodes in children. J Pak Med Assoc 1991; 41: 185-87.

Abdel-Fattah AM, Matsumoto K, Watanabe H. Antinociceptive effects of Nigella sativa oil and its major component, thymoquinone, in mice. Eur J Pharmacol 2000; 400: 89-97.

Akhtar AH, Ahmed KO, Gilani SN. Antiulcer effect of aqueous extracts of Nigella sativa and pongamia pinnata in rats. Fitoterapia 1996; 67: 195-99.

El-Tahir KE, Ashour MM, Al-Harbi MM. The cardiovascular actions of the volatile oil of the black seed (Nigella sativa) in rats: elucidation of the mechanism of action. Gen Pharmacol. 1993; 24: 1123-31.

Zaoui A, Cherrah Y, Lacaille-Dubois MA, Settaf A, Amarouch H, Hassar M. Diuretic and hypotensive effects of Nigella sativa in the spontaneously hypertensive rat. Therapie 2000; 55: 379-82.

Nanjmi A, Nasiruddin M, Khan RA, Haque SF. Indigenous herbal product Nigella sativa proved effective as an antihypertensive in metabolic syndrome. Asian J Pharm Clin Res 2013; 6(1): 61-64.

Gilani AH, Aziz N, Khurram IM, Chaudhary KS, Iqbal A. Bronchodilator, spasmolytic and calcium antagonist activities of Nigella sativa seeds (Kalonji): a traditional herbal product with multiple medicinal uses. J Pak Med Assoc 2001; 51: 115-20.

Daba MH, Abdel-Rahman MS. Hepatoprotective activity of thymaoquinone in isolated rat hepatocytes. Toxicol Lett 1998; 95: 23-29.

Burits M, Bucar F. Antioxident activity of Nigella sativa essential oil. Phytother Res 2000; 14: 323-28.

Kanter M, Coskun O, Budancamanak M. Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats. World J Gastroenterol 2005; 11: 6684-88.

Sultan MT, Butt MS, Anjum FM, Jamil A, Akhtar S, Nasir M. Nutritional profile of indigenous cultivar of black cumin seeds and antioxidant potential of its fixed and essential oil. Pak J Bot 2009; 41: 1321-30.

Houghton PJ, Zarka R, Heras B, Hoult JR. Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes a membrane lipid peroxidation. Planta Med 1995; 61: 33-36.

Nagi M, Mansour M. Protective effect of thymoquinone against doxorubicin-induced cardio toxicity in rat. A Possible mechanism of protection. Pharm Res 2000; 41: 283-89.

Nagi MN, Alam K, Badary OA, Al-Shabanah OA, Al-Sawaf HA, Al-Bekairi AM. Thymoquinone protects against carbon tetrachloride hepatotoxicity in mice via an antioxidant mechanism. Biochem Mol Biol Int 1999; 47: 53-59.

Al-Ghamdi MS. Protective effect of Nigella sativa seeds against carbon tetrachloride-induced liver damage. Am J Chin Med 2003; 31: 721-28.

Schumann G, Klauke R. New IFCC reference procedures for the determination of catalytic activity concentrations of five enzymes in serum: Preliminary upper reference limits obtained in hospitalized subjects. Clinica Chimica Acta 2003; 327: 69-79.

Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959; 82: 70-77.

Plaser ZA, Cushman LL, Johnson BC. Estimation of product of lipid peroxidation (malondialdehyde) in biochemical systems. Anal Biochem 1966; 16: 359-64.

Meral I, Yener Z, Kahraman T, Mert N. Efect of Nigella sativa on glucose concentration lipid peroxidation, antioxidant defense system and liver damage in experimentally-induced diabetic rabbits. J Vet Med 2001; 48: 593-99.

Elhabib EM, Homeida MMA, Adam SEI. Effect of combined paracetamol and Cuminum cyminum or Nigella sativa use in Wister rats. J Pharmacol Toxicol 2007; 2: 653-59.

Al-Kubaisy K, Al-Noaemi M.A Protective role of Nigella sativa oil against the harmful effect of CCl4 on the liver cells. The internet journal of nutrition and wellness 2007; 3: 1-12.