Effect of Non-Hexane Fraction of Ethanol Extract of Noni Fruit (Morinda citrifolia L.) on ALT Activities, Creatinine Levels and TCD4+/TCD8+ Cell Ratios in The Isoniazid-Induced Female Rats

Nuraini Ekawati

Abstract


     Isonicotinyl hydrazine (isoniazid) is the most effective drug for antituberculosis treatment. During the metabolism process of isoniazid, some reactive metabolites might be generated. Thus reactive metabolite possibly responsible for several side effect through the mechanism of oxidative stress. Some of the side effects are liver damage, kidney damage, and autoimmune disorder characterized by decreased TCD4+/TCD8+ cell ratio.

               Noni (Morinda citrifolia L.) contains phenolic compounds such as scopoletin, quercetin, and rutin, which have various biological activities including antioxidant, antiinflammatory, and hepatoprotective activities. The antioxidant activity of phenolic compounds is through the mechanism of radical scavenging, inhibit formation of free radicals, therefore tissue damage can be prevented.

The purpose of this study was to determine chemical constituens of non n-hexane fraction of Noni fruit extract (test sample) and to determine whether test sample can reduce the side effect of isoniazid by measuring ALT activity, creatinine level, and TCD4+/TCD8+ cell ratio. Total 35 Wistar rats, aged 6-8 weeks, were divided into 7 groups. Group I as normal control group received 0.25% DMSO, group II received isoniazid 150 mg/kgBW, group III received ethanol extract of Noni fruit 250 mg/kgBW, group IV received isoniazid 150 mg/kgBW + test sample 15 mg/kgBW, group V received isoniazid 150 mg/kgBW + test sample 30 mg/kgBW,  group VI received isoniazid 150 mg/kgBW + test sample 75 mg/kgBW, and group VII received test sample 75 mg/kgBW, each with a volume of 20 mL/kg per oral/day for 8 weeks. Blood samples was collected at weeks 0, 4, 6 and 8 to evaluate the ALT activity, creatinine level, and TCD4+/TCD8+ cell ratio taken. Chemical constituens of test sample was conducted using TLC method.

Qualitative analysis indicated that test sample contains alkaloid, phenolic, and flavonoid compound. Test sample could reduce ALT level and increase TCD4+/TCD8+ cell ratio, but couldn’t reduce creatinine level of isoniazide-induced female Wistar rat.

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References


Alitheen, N.B., Manaf, A.A., Yeap, S.K., Shuhaimi, M., Nordin, L., dan Mashitoh, A.R., 2010. Immunomodulatory Effects of Damnacanthal Isolated from Roots of Morinda elliptica. Pharmaceutical Biology, 48: 446–452.

Domitrovic, R., Jakovac, H., Vasiljev Marchesi, V., Vladimir-Knežević, S., Cvijanović, O., Tadić, Ž., dkk., 2012. Differential Hepatoprotective Mechanisms of Rutin and Quercetin in CCl4-intoxicated BALB/cN Mice. Acta Pharmacologica Sinica, 33: 1260–1270.

Evans, D.A., Bullen, M.F., Houston, J., Hopkins, C.A., dan Vetters, J.M., 1972. Antinuclear Factor in Rapid and Slow Acetylator Patients Treated with Isoniazid. Journal of medical genetics, 9: 53.

Fukino, K., Sasaki, Y., Hirai, S., Nakamura, T., Hashimoto, M., Yamagishi, F., dkk., 2008. Effects of N-acetyltransferase 2 (NAT2), CYP2E1 and Glutathione-S-transferase (GST) Genotypes on The Serum Concentrations of Isoniazid and Metabolites in Tuberculosis Patients. The Journal of Toxicological Sciences, 33: 187–195.

Hayes, J.L.K., Evelyn R., 1996. Farmakologi : Pendekatan Proses Keperawatan. EGC, Jakarta.

Huang, Y.-S., Chern, H.-D., Su, W.-J., Wu, J.-C., Lai, S.-L., Yang, S.-Y., dkk., 2002. Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug–induced hepatitis. Hepatology, 35: 883–889.

Kahkonen, M.P., Hopia, A.I., Vuorela, H.J., Rauha, J.-P., Pihlaja, K., Kujala, T.S., dkk., 1999. Antioxidant Activity of Plant Extracts Containing Phenolic Compounds. Journal of Agricultural and Food Chemistry, 47: 3954–3962.

Kang, S.Y., Sung, S.H., Park, J.H., dan Kim, Y.C., 1998. Hepatoprotective activity of scopoletin, a constituent ofSolanum lyratum. Archives of Pharmacal Research, 21: 718–722.

Krishnaiah, D., Nithyanandam, R., dan Sarbatly, R., 2012. Phytochemical Constituents and Activities of Morinda Citrifolia L. INTECH Open Access Publisher.

Lopez-Novoa, J.M., Quiros, Y., Vicente, L., Morales, A.I., dan Lopez-Hernandez, F.J., 2011. New Insights Into The Mechanism of Aminoglycoside Nephrotoxicity: An Integrative Point of View. Kidney International, 79: 33–45.

Manuele, M.G., Ferraro, G., Barreiro Arcos, M.L., López, P., Cremaschi, G., dan Anesini, C., 2006. Comparative immunomodulatory effect of scopoletin on tumoral and normal lymphocytes. Life Sciences, 79: 2043–2048.

Mohd Zin, Z., Abdul Hamid, A., Osman, A., Saari, N., dan Misran, A., 2007. Isolation and Identification of Antioxidative Compound from Fruit of Mengkudu (Morinda citrifolia L.). International Journal of Food Properties, 10: 363–373.

Padmavathy, S., Jeyachandran, R., dan Cindrella, L., 2009. Ethnopharmacological Importance of Morinda citrifolia L. African Journal of Traditional, Complementary and Alternative Medicines (AJTCAM), 6: 325.

Perl, A., 2013. Oxidative Stress in The Pathology and Treatment of Systemic Lupus Erythematosus. Nature Reviews Rheumatology, 9: 674–686.

Tostmann, A., Boeree, M.J., Aarnoutse, R.E., De Lange, W.C.M., Van Der Ven, A.J.A.M., dan Dekhuijzen, R., 2008. Antituberculosis drug-induced hepatotoxicity: Concise up-to-date review. Journal of Gastroenterology and Hepatology, 23: 192–202.

Vasoo, S., 2006. Drug-induced Lupus: An Update. Lupus Journal, 15: 757–761.

Windish, H.P., 2008. Regulation of Immunopathology in Mycobacterium Tuberculosis Infection. ProQuest, Ann Arbor.

Yew, W.W. dan Leung, C.C., 2006. Antituberculosis Drugs and Hepatotoxicity. Respirology, 11: 699–707.

Ziaee, A., Zamansoltani, F., Nassiri, A.M., HAdigol, T., dan Ghasemi, M., 2011. Study of The Hepatoprotective Effects of Rutin on Acetaminophen and Carbon Tetraclhoride-induced Liver Injury in Rats. Journal of Pharmaceutical Science, 17: 35–42.




DOI: http://dx.doi.org/10.20961/jpscr.v2i02.14388

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