POTENTIAL ROLE OF ANNONA SQUAMOSA LINN EXTRACT AND N-ACETYL CYSTEINE IN MANAGEMENT OF RIFAMPICIN-INDUCED HEPATOXICITY IN RATS

Authors

  • BOSY AZMY ABD EL MOTELP Assistant Professor of Physiology at Zoology Department, Faculty of Women for Arts, Science and Education, Ain Shams University, Asmaa Fahmy Street Heliopolis, Cairo, Egypt
  • HADER FAWZY DARWISH Demonstrator at Zoology Department, Faculty of Women for Arts, Science and Education, Ain Shams University, Asmaa Fahmy Street Heliopolis, Cairo, Egypt
  • SAMIHA MOHAMED ABD ELDAYEM Professor of Physiology at Zoology Department, Faculty of Women for Arts, Science and Education Ain Shams University, Asmaa Fahmy Street Heliopolis, Cairo, Egypt
  • FATMA MOKHTAR FOUDA Assistant Professor of Physiology at Zoology Department, Faculty of Women for Arts, Science and Education, Ain Shams University, Asmaa Fahmy Street Heliopolis, Cairo, Egypt

DOI:

https://doi.org/10.22159/ijpps.2020v12i8.38424

Keywords:

Rifampicin, hepatotoxicity, Annona Squamosa, N-acetyl Cysteine, Inflammation, Apoptosis

Abstract

Objective: Rifampicin (RIF) could be a recognized therapeutic and preventive agent against tuberculosis. Still, high rates of many side effects and symptoms related to hepatotoxicity have identified during treatment. So, the current study was aimed to evaluate the antioxidant and hepatoprotective activity of methanolic extract of Annona Squamosa Linn (MEAS) and N-Acetyl Cysteine (NAC) against RIF induced hepatic injury in male rats.

Methods: The hepatoprotective effects of MEAS (500 mg/kg b.wt.) and NAC (100 mg/kg b.wt.) or co-treatment were assessed in a model of hepatotoxicity by RIF (300 mg/kg b. wt.) in male rats daily for 21 d. Moreover, bilirubin, total protein, albumin, ALT, AST, ALP, GGT, MDA, and GSH were estimated. In addition, the levels of IL-6, IL-10, 8(OH)dG, and Bcl2 were evaluated.

Results: The oral administration of MEAS and NAC or their combination resulted in significant reductions in the levels of bilirubin, albumin, hepato-specific markers namely ALT, AST, ALP, GGT, and MDA as compared to the RIF group. Furthermore, MEAS and NAC or the combination of MEAS and NAC treatment significantly up-regulated the levels of total protein, glutathione reductase with concomitant decrease in inflammatory marker level IL-6 and apoptotic marker level 8(OH)dG as well as increment the level of anti-inflammatory marker IL-10 and anti-apoptotic marker Bcl2 as compared to the RIF group. Histological examination of the liver tissue indicated that co-treatment with MEAS and NAC completely abolished the inflammation and degeneration in hepatocytes and restore the liver tissue to its normal structure.

Conclusion: The present findings demonstrated that a co-treatment of MEAS and NAC seems to be more productive and curative than alone MEAS or NAC treatment and strongly compensated the liver damage induced by RIF.

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Author Biographies

BOSY AZMY ABD EL MOTELP, Assistant Professor of Physiology at Zoology Department, Faculty of Women for Arts, Science and Education, Ain Shams University, Asmaa Fahmy Street Heliopolis, Cairo, Egypt

Department of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University.

HADER FAWZY DARWISH, Demonstrator at Zoology Department, Faculty of Women for Arts, Science and Education, Ain Shams University, Asmaa Fahmy Street Heliopolis, Cairo, Egypt

Zoology Department, Faculty of Women for Arts, Science and Education, Ain Shams University

SAMIHA MOHAMED ABD ELDAYEM, Professor of Physiology at Zoology Department, Faculty of Women for Arts, Science and Education Ain Shams University, Asmaa Fahmy Street Heliopolis, Cairo, Egypt

Zoology Department, Faculty of Women for Arts, Science and Education, Ain Shams University

FATMA MOKHTAR FOUDA, Assistant Professor of Physiology at Zoology Department, Faculty of Women for Arts, Science and Education, Ain Shams University, Asmaa Fahmy Street Heliopolis, Cairo, Egypt

Zoology Department, Faculty of Women for Arts, Science and Education, Ain Shams University, Asmaa Fahmy Street Heliopolis, Cairo, Egypt

References

Kumar V, Sharma A, Machawal L, Khan AA. the beneficial role of herbal hepatoprotectants: a novel approach to prevent hepatotoxicity due to antituberculosis treatment. J Biomed Pharm Res 2013;2:181-93.

WHO. Global TB report. 20th edition. World health organization; 2015.

Kishore PV, Palaian S, Paudel R, Mishra P, Prabhu M, Shankar PR. Drug-induced hepatitis with antitubercular chemotherapy: challenges and difficulties in treatment. Kathmandu Univ Med J 2007;5:256-60.

Baskaran UL, Sabina EP. Clinical and experimental research in antituberculosis drug-induced hepatotoxicity: a review. J Integr Med 2017;15:27–36.

Singh J, Garg PK, Tandon RK. Hepatotoxicity due to antituberculosis therapy. Clinical profile and reintroduction of therapy. J Clin Gastroenterol 1996;22:211-4.

Sodhi CP, Rana SV, Mehta SK, Vaiphei K, Attari S, Mehta S, et al. Study of oxidative-stress in isoniazid-rifampicin induced hepatic injury in young rats. Drug Chem Toxicol 1997;20:255-69.

Aruoma OI. Methodological considerations for characterizing potential antioxidant actions of bioactive components in food plants. Mutat Res 2003;920:523–24.

Suja SR, Latha PG, Pushpangadan P, Rajasekharan S. Aphrodisiac property of Helminthostachys zeylanica in mice. J Trop Med Plant 2002;3:191–5.

Mariod AA, Abdelwahab SI, Elkheir S, Ahmed YM, Fauzi PN, Chuen CS, et al. Antioxidant activity of different parts from Annona squamosa and Catunaregam nilotica methanolic extract. Acta Sci Pol Technol Aliment 2012;11:249-58.

Kaleem M, Asif M, Ahmed QU, Bano B. Antidiabetic and antioxidant activity of Annona Squamosa extract in streptozotocin-induced diabetic rats. Singapore Med J 2006;47:670-5.

Uduma MSTS, Sundarapandian R, Muthumanikkam A, Kalimuthu G, Parameswari A, Srinivas TRV, et al. Protective effect of methanolic extract of Annona Squamosa Linn in isonizid-rifampicin induced hepatoxicity in rats. Pak J Pharm Sci 2011;24:129-34.

Nakano H, Boudjema K, Jaeck D, Alexandre E, Imbs P, Chenard MP, et al. Amelioration of hepatocellular integrity and inhibition of sinusoidal oxidative stress by N-acetylcysteine pretreatment in cold ischemia-reperfusion injury of rat liver. Eur Surg Res 1996;28:245-55.

Tobwala S, Khayyat A, Fan W, Ercal N. Comparative evaluation of N-acetylcysteine and N-acetylcysteineamide in acetaminophen-induced hepatotoxicity in human hepatoma HepaRG cells. Exp Biol Med 2005;240:261–72.

Thampi A, Joy J, Kumar G, Sreekrishnan TP, Ajith V. N-acetylcysteine in non acetaminophen-related acute liver injury. Asian J Pharm Clin Res 2016;9:7-8.

Sen H, Deniz S, Yedekci AE, Inangil G, Muftuoglu T, Haholu A, et al. Effects of dexpanthenol and N-acetylcysteine pretreatment in rats before renal ischemia/reperfusion injury. Ren Fail 2014;36:1570–4.

Attri S, Rana SV, Vaiphei K, Sodhi CP, Katyal R, Goel RC, et al. Isoniazid-and rifampicin-induced oxidative hepatic injury protection by N-acetylcysteine. Hum Exp Toxicol 2000;19:517-22.

Lian Y, Zhao J, Xu P, Wang Y, Zhao J, Jia L, et al. Protective effects of metallothionein on isoniazid and rifampicin-induced hepatotoxicity in mice. PLoS One 2013;8:0-72058.

Rana SV, Attri S, Vaiphei K, Pal R, Attri A, Singh K. Role of N-acetylcysteine in the rifampicin-induced hepatic injury of young rats. World J Gastroenterol 2006;12:287-91.

Kaplan A. Bilirubin clin chem the C. V. mosby co. st louis. Toronto Princeton 1984;436,650:1238-41.

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951;193:265-75.

Doumas BT, Biggs HG. Standard methods of clinical chemistry, Academic Press, NY; 1976;7:175.

Tietz NW. Fundamentals of clinical chemistry. 2nd Edn. WB Saunders. Philadelphia; 1976. p. 878.

Belfield A, Goldberg DM. Revised assay for serum phenyl phosphatase activity using 4-amino antipyrine. Enzyme 1971;12:561-73.

Szasz G, Persijn JP. Method for γ–glutamyltransferase (γGT). Clin Chem Clin Biochem 1974;12:228.

Ohkawa H, Ohish N, Yagi K. Assay for lipid peroxidase in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.

Beutler E, Duron O, Kelly BM. Improved method of the determination of blood glutathione. J Lab Clin Med 1963;61:882-8.

Boulanger MJ, Chow D, Brevnova EE, Garcia KC. Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex. Science 2003;300:2101-4.

Eskdale J, Kube D, Tesch H, Gallagher G. Mapping of the human IL10 gene and further characterization of the 5' flanking sequence. Immunogenetics 1997;46:120–8.

Banchroft JD, Stevens A, Turner DR. Theory and practice of histological techniques. 4th ed. New York, London, San Francisco, Tokyo: Churchil Livingstone; 1996. p. 766.

Bedi O, Bijjem KRV, Kumar P, Gauttam V. Herbal induced hepatoprotection and hepatotoxicity: a critical review. Indian J Physiol Pharmacol 2016;60:6-21.

Rafiq S, Iqbal T, Jamil A, Khan FH. Pharmacokinetic studies of rifampicin in healthy volunteers and tuberculosis patients. Int J Agric Biol 2010;12:391–5.

Jadhav VB, Thakare VN, Suralkar AA, Deshpande AD, Naik SR. Hepatoprotective activity of Luffa acutangula. Indian J Exp Biol 2010;48:822-9.

Shabana MB, Ibrahim HM, Khadre SEM, Elemam MG. Influence of rifampicin and tetracycline administration on some biochemical and histological parameters in albino rats. J Basic Appl Zool 2012;65:299–308.

Kissler HJ, Hauffen J, Hennig R, Gepp H, Schwille PO. Glucose and lipid metabolism after liver transplantation in inbred rats: consequences of hepatic denervation. Metabolism 2005;54:881-90.

Saraswathy SD, Devi CSS. Modulating effect of Liv.100, an ayurvedic formulation on antituberculosis drug-induced alterations in rat liver microsomes. Phytother Res 2001;15:501–5.

Balakrishnan A, Menon PV. Effect of hesperdin on nicotine toxicity and histological studies. Toxicol Mechan Methods 2007;17:233-9.

Sheweita SA, Abd EM, Bastawy M. Carbon tetrachloride-induced changes in the activity of phase ii drug-metabolizing enzyme in the liver of male rats: role of antioxidants. Toxicology 2001;165:217-24.

Hussain T, Siddiqui HH, Fareed S, Vijiayakumar M, Rao CV. Evaluation of chemo-preventive effect of Fumaria indica against N-nitroso-diethylamine and CCL4-induced hepatocellular carcinoma in wistar rats. Asian Pac J Trop Med 2012;5:623-9.

Farrell GC. Drug-induced liver disease. Churchill Living Stone, London; 1995. p. 413–30.

Qader GI, Aziz RS, Ahmed ZA, Abdullah ZF, Hussain SA. Protective effects of quercetin against isoniazid and rifampicin induced hepatotoxicity in rats. Am J Pharmacol Sci 2014;2:56-60.

Farazi A, Sofian M, Jabbarias M. Efficacy of N-acetylcysteine on prevention of antituberculosis drug-induced hepatotoxicity. World J Med Sci 2015;12:413-8.

Ayala A, Munoz MF, Arguelles S. Lipid peroxidation: production, metabolism and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Med Cell Long 2014;6:360-438.

Abd El Dayem MS, Fouda MF, Ali HAE, Abd El Motelp BA. The antitumor effects of tetrodotoxin and/or doxorubicin on Ehrlich ascites carcinoma-bearing female mice. Toxicol Indus Health 2012:1-14. https://doi.org/10.1177/ 0748233711434955.

Serki E, Hemmati M, Pourtalebi Firoozabadi A. A preliminary study of comparison of the preventive and therapeutic effect of green and white tea against rifampicin-induced chronic hepatotoxicity in rats. Am J Clin Exper Med 2017;5:145-50.

Meister A. Glutathione deficiency produced by inhibition of its synthesis, and its reversal; applications in research and therapy. Pharmacol Ther 1991;51:155–94.

Kumar S, Gangulay NK, Kohli KK. Inhibition of cellular glutathione biosynthesis by rifampicin in Mycobacterium smegmatis. Biochem lnt 1992;26:468-76.

Nandhakumar E, Indumathi P. In vitro antioxidant activities of methanol and aqueous extract of Annona squamosa (L.) fruit pulp. J Acupunct Meridian Stud 2013;6:142-8.

Kalidindi N, Thimmaiah NV, Jagadeesh NV, Nandeep R, Swetha S, Kalidindi B, et al. Antifungal and antioxidant activities of organic and aqueous extracts of Annona squamosa Linn leaves. J Food Drug Anal 2015;23:795-802.

Hamid ZA, Tan HY, Chow PW, Harto KAW, Chan CY, Mohamed J, et al. The role of n-acetylcysteine supplementation on the oxidative stress levels, genotoxicity and lineage commitment potential of ex vivo murine hematopoietic stem/progenitor cells. Sultan Qaboos Univ Med J 2018;18:130-6.

Dash M, Maity M, Dey A, Perveen H, Khatun S, Jana L, et al. The consequence of NAC on sodium arsenite-induced uterine oxidative stress. Toxicol Rep 2018;5:278–87.

Chang C, Yen Fu C, Vin Cent W, Chin Chung S, Chih Hsin L, Jann Yuan W, et al. Acute kidney injury due to anti-tuberculosis drugs: a five-year experience in an aging population. BMC Infect Dis 2014;14:23.

Müller M, Wandel S, Colebunders R, Attia S, Furrer H, Egger M, et al. Immune reconstitution inflammatory syndrome in patients starting antiretroviral therapy for HIV infection: a systematic review and meta-analysis. Lancet Infect Dis 2010;10:251–61.

Nathiya S, Rajaram S, Abraham P. Hesperidin alleviates antitubercular drug induced oxidative stress, inflammation and apoptosis in rat liver. Internat J Biomed Res 2016;7:439-46.

Hoek JB, Pastorino JG. Ethanol, oxidative stress, and cytokine-induced liver cell injury. Alcohol 2002;27:63–8.

Reliene R, Schiestl RH. Antioxidant n-acetyl cysteine reduces the incidence and multiplicity of lymphoma in atm deficient mice. DNA Repair (Amst) 2006;5:852–9.

Liu B, Andrieu Abadie N, Levade T, Zhang P, Obeid LM, Hannun YA, et al. Glutathione regulation of neutral sphingomyelinase in tumor necrosis factor-alpha-induced cell death. J Biol Chem 1998;273:11313–20.

Kang R, Li R, Dai P, Li Z, Li Y, Li C, et al. Deoxynivalenol induced apoptosis and inflammation of IPEC-J2 cells by promoting ROS production. Environ Pollut 2019;251:689-69.

Abrar H, Naqvi SNH, Ahmed MR, Ali AB, Yasin H, Perveen R, et al. Effect of propranolol on hepatic blood flow for reduction of the hepatotoxicity of rifampicin in rabbits. Med Forum 2017;28:105-9.

Awodele O, Akintonwa A, Osunkalu VO, Coker HAB. Modulatory activity of antioxidants against the toxicity of rifampicin in vivo. Rev Inst Med Trop S Paulo 2010;52:43–6.

Published

01-08-2020

How to Cite

MOTELP, B. A. A. E., H. F. DARWISH, S. M. A. ELDAYEM, and F. M. FOUDA. “POTENTIAL ROLE OF ANNONA SQUAMOSA LINN EXTRACT AND N-ACETYL CYSTEINE IN MANAGEMENT OF RIFAMPICIN-INDUCED HEPATOXICITY IN RATS”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 12, no. 8, Aug. 2020, pp. 117-23, doi:10.22159/ijpps.2020v12i8.38424.

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