Hepatoprotective Effect of Citrus Sinensis Peel Extract Against Isoniazid and Rifampicin-induced Liver Injury in Wistar Rats

https://doi.org/10.22146/mot.45762

Edward Kosasih(1*), Linda Chiuman(2), I Nyoman Ehrich Lister(3), Edy Fachrial(4)

(1) Master of Biomedical Science, Faculty of Medicine, Universitas Prima Indonesia
(2) Master of Biomedical Science, Faculty of Medicine, Universitas Prima Indonesia
(3) Master of Biomedical Science, Faculty of Medicine, Universitas Prima Indonesia
(4) Laboratory of Biology Molecular, Faculty of Medicine, Universitas Prima Indonesia
(*) Corresponding Author

Abstract


Tuberculosis (TB) is one of the leading causes of death in developing countries. One of the problems in controlling TB disease is that most anti-tuberculosis drugs are hepatotoxic. Citrus sinensis peel extract is the rich source of secondary metabolites with high potential effectiveness as an antioxidant. In the present study, we evaluate the hepatoprotective effect of Citrus sinensis peel ethanolic extract (CSPEE) on isoniazid and rifampicin-induced liver injury in Wistar rats. Twenty five adult male Wistar rats were divided into 5 groups of 5 each : control,  (INH+RIF) (50 mg/kg bw once a day for 14 days), (INH+RIF) + various dose of CSPEE (300, 450, 600 mg/kg bw).  CSPEE was given orally once a day for 14 days followed by administration of INH + RIF suspension. The measurement of serum ALT and AST were carried out on the 15th day. Histopathologic examination of the liver was also performed. The Serum ALT and AST of the rats that induced with INH + RIF were increased significantly (P<0.001) compare to those of control groups, and the histopathologic slides showed steatosis, vacuolation and necrosis of hepatic cells. The serum ALT and AST in groups treated with CSPEE were not significantly different (p>0.05) with those of control groups. The serum ALT and AST and histopathological examination of the liver of the group that administered 600 mg/kg CSPEE were closest to normal rats. Citrus sinensis peel extract exhibits hepatoprotective effect on liver injury induced with INH + RIF in Wistar rats.


Keywords


citrus sinensis peel; drug-induced liver injury; isoniazid; rifampicin; Wistar rat

Full Text:

PDF


References

Abdel-Ghaffar,O., Mahmoud,S.T., Said,A.A., and Sanad,F.A-A.Y.,2017, ‘Hepato-protective Effect of Rutin Against Oxidative Stress of Isoniazid in Albino Rats’, Int. J. Pharmacol., 13 (6): 516-528. 

Chowdhury,A., Santra,A., Kundu,S., Mukherjee,A., Pandit,A., Chaudhuri,S., and Dhali,G.H., 2001, ‘Induction of oxidative stress in antitubercular drug-induced hepatotoxicity’. Indian Journal of Gastroenterology, vol 20 May-June.            

David,S dan Hamilton, J.P., 2010. Drug-induced Liver Injury. US Gastroenterol Hepatol Rev.6:73-80.

Delaney,J., Timbrell,J.A., 1995, ‘Role of cytochromeP450 in hydrazine toxicity in Isolated hepatocytes invitro’ [abstract]. Xenobiotica ;25:1399– 410.

Deck,D.H.,& Winston L.G., 2012. ‘Antimycobacterial Drugs’ in Katzung,B.G., Master,S.B., Trevor,A.J., (Eds.). Basic & Clinical Pharmacology, 12th ed. The McGraw-Hill Inc. New York.

Departemen kesehatan Republik Indonesia, 1995. Materia medika Indonesia. Jilid VI. Departemen Kesehatan R.I. Jakarta

Eminzade,S., Uras,F. and Izzettin,F.V., 2008, ‘Sylimarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals’, Nutrition & Metabolism, 5:18 doi:10.1186/1743-7075-5-18

Ernawita, Wahyuono,R.A., Hesse,J., Hipler, UC., Elsner,P. and Böhm,V., 2017 ‘In Vitro Lipophilic Antioxidant Capacity, Antidiabetic and Antibacterial Activity of Citrus Fruits Extracts from Aceh, Indonesia. Antioxidants 2017, 6, 11; doi:10.3390/antiox6010011. Available at: www.mdpi.com/journal/antioxidants

Finkel,R., Clark,M.A., and Cubeddu,L.X., (2009), ‘Lippincotts Illustrated Reviews: Pharmacology’. Edisi 4. Editor bahasa Indonesia: dr.Adhy Tjahyanto dan dr.Carolina Salim. Penerbit Buku Kedokteran EGC Jakarta. Hal.477.

Hasan,M., Tamanna,N. and Haque,A., 2017, ‘Biochemical and histopathological profiling of Wistar rat treated with Brassica napus as a supplementary feed’. Food science and human wellness 7 (2018)77-82.

Ikeokwu,A.L., 2014, ‘Studies on in-vivo Antioxidant and Hepatoprotective properties of Citrus sinensis (L.) Osbeck peel extract in wistar rats’, Thesis. Departement of Pharmacology and Therapeutic Faculty of Pharmaceutical sciences Ahmadu Bello University, Zaria,Negeria. Available online at http://kubanni.abu.edu.ng/

Kementerian Kesehatan Republik Indonesia, 2017. ‘Data dan Informasi Profil Kesehatan Indonesia 2017’. Available at: http://www.depkes.go.id/resources/download/pusdatin/profil-kesehatan-indonesia/Data-dan-Informasi_Profil-Kesehatan-Indonesia-2017.pdf

Mehmood,B., Khurshid Dar,K., Ali,S., Awan,U.A., Nayyer1,A.Q., Ghous,T. and Andleeb,S., 2015, ‘In vitro assessment of antioxidant, antibacterial and phytochemical analysis of peel of Citrus sinensis. Available online at:

https://www.researchgate.net/publication/257932280

Muhtadi, Haryoto, Azizah,T.,  Suhendi,A., Khong,H.Y., 2015. Antidiabetic and antihypercholes-terolemic activities of Citrus sinensis peel: in vivo study. Natl J Physiol Pharm Pharmacol 2015;5:382-385.


Available at:

https://www.ejmanager.com/mnstemps/28/281438068486.pdf?t=1536841 313

Nolan,C.M., Goldberg,S.V., Buskin,S.E.,1999, ‘Hepatotoxicity associated with isoniazid preven-tive therapy: a 7-year survey from a public health tuberculosis clinic’. JAMA; 281: 1014–18. 

Omodamiro,O.D. and Umekwe, J.C., 2013. Evaluation of anti-inflammatory, antibacterial and antioxidant properties of ethanolic extracts of Citrus sinensis peel and leaves. J. Chem. Pharm. Res., 2013, 5(5):56-66. Availaible online at www.jocpr.com

Ostapowicz,G., Fontana,R.J., Schiødt,F.V., Larson,A., Davern,T.J., Han,S.H.et.al.,2002, ‘Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States (Abstract)’, Ann Intern Med. ;137 (12): 947-54.

Pal,R., Vaiphei,K., Sikander,A., Singh,K., Rana, S.V., 2006, ‘Effect of garlic on isoniazid and rifampicin-induced hepatic injury in rats’. World J Gastroenterol 12: 636–639.

Putnik,P., Kovaˇcevi´c,D.B., Jambrak,A.R., Barba,F.J., Cravotto,G., Binello,A., et.al., 2017, ‘Innovative “Green” and Novel Strategies for the Extraction of Bioactive Added Value Compounds from Citrus Wastes—A Review’, Molecules, 22, 680; doi:10.3390  /molecules 22050680.     

Rekha,S.S. and Bhaskar,M., 2013, ‘In Vitro Screening and Identification of anti-oxidant activities of orange (citrus sinensis) peels extract in different solvents’. Int.J.Pharma Bio Sci,: Oct; 4(4): P(405-412).

Sarmak,G.R., Immanuel,C., Kailasam,S., Narayana,A.S., Venkatesan,P.,1986,’Rifampin-induced release of hydrazine from isoniazid. A possible cause of hepatitis during treatment of tuberculosis with regimens containing isoniazid and rifampin. Am Rev Respir Dis. 133(6):1072-5. 

Selmi,A., Rtibi,K., Grami,D., Sebai,H. and Lamjed Marzouki,L.,2017, ‘Protective effects of orange (Citrus sinensis L.) peel aqueous extract and hesperidin on oxidative stress and peptic ulcer induced by alcohol in rat. Lipids in Health and Disease16:152 DOI 10.1186/s12944-017-0546-y.


Selvi R.S., Kumar,R.Z.A., and Bhaskar,A., 2016, ‘Phytochemical investigation and in vitro anti-oxidant activity of Citrus sinensis peel extract’. Der Pharmacia Lettre, 8 (3):159-16.

Selvi R.S., Kumar,R.Z.A., and Bhaskar,A., 2016, ‘Phytochemical investigation and in vitro anti-oxidant activity of Citrus sinensis peel extract’. Der Pharmacia Lettre, 8 (3):159-16.

Shetty,S.B., Mahin-Syed Ismail,P., Varghese,S., Thomas-George,B., Kandathil-Tha-juraj,P., Baby,D., et al., 2015. Antimicrobial effects of Citrus sinensis peel extracts against dental caries bacteria: An in vitro study.  http://dx.doi.org/10.4317/jced.52493

Setyawati,I., Anggraeni,R., 2018. Effectiveness of Sweet Orange Peel Extract (Citrus sinensis) on the Improvement of Liver Functions of Animal Trials Induced by Cigarette Smoke. J Young Pharm, 2018; 10(2) Suppl: s132-s135. Available at: http://www.jyoungpharm.org/article/1242

Tasduq, S.A., Kaiser,P., Sharma,SC., Johri,R.K., 2007, ‘Potentiation of isoniazid-induced liver toxicity by rifampicin in a combinational therapy of antitubercular drugs (rifampicin, isoniazid and pyrazinamide) in Wistar rats : A toxicity profile study. (abstract)’. Hepatol Res.Oct;37(10):845-53.          

Tostman,A., Boeree,M.J., Aartnoutse,R.E., de Lange,W.C.M., van der Ven,  A.J.M.,  and Dekhuijzen,R., 2007, ‘Antituberculosis drug-induced hepatotoxicity: Concise up-to-date review’.  https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1440-1746.2007.05207

WHO, 2017. Global Tuberculosis Report 2017.  Available at:

             http://www.who.int/tb/publications/global_report/gtbr2017_main_text.pdf


 



DOI: https://doi.org/10.22146/mot.45762

Article Metrics

Abstract views : 228 | views : 223

Refbacks

  • There are currently no refbacks.




Copyright (c) 2019 Majalah Obat Tradisional

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

©Majalah Obat Tradisional (Trad.Med.J) 
Faculty of Pharmacy
Universitas Gadjah Mada