Pengaruh Pemberian Curcumin Terhadap Perbaikan Fungsi Hepar Tikus Putih (Rattus Novergicus) yang diinduksi Parasetamol Dosis Tinggi

Yolanda Esperanza, Sulistiana Prabowo, Fitri Handajani

Abstract


Paracetamol has analgesic properties comparable to NSAIDs, but paracetamol have minimal side effects. Paracetamol is metabolized via sulfation and glucuronidation conjugation which is then excreted in the urine. A small part of the paracetamol has been changed to NAPQI. NAPQI will be detoxified by gluthathione. In high doses, there in an increase in NAPQI and a decrease in glutathione levels that results in oxidative stress and liver cell necrosis. Curcumin is often used as a traditional medicine to treat liver disease where it contains phenolic groups capable to scavenge free radicals. Curcumin extract can improve cellular responses to oxidative stress such as increasing the expression of Nrf2, SOD, and gluthathione. The purpose of this research was to know the effect of curcumin on the improvement of liver function in white rats (Rattus novergicus) induced by high dose  paracetamol. The design of this research was a descriptive research using literature studies from at least 15 international journals indexed by Scimago or national journals indexed by Sinta published in 2015-2020. Based on the journals used in this research, giving curcumin at a dose of 200 mg/kg BW/day for 2 weeks was effective in significantly increasing gluthathione levels in rats receiving high dose paracetamol. Giving curcumin at a dose of 100 mg/kg BW/day for 7 days can reduce AST and ALT activity in rats receiving high dose paracetamol, but the dose of curcumin that was more effective in reducing AST and ALT activity was 200 mg/kg BW/day for 2 weeks. This is because of curcumin which functions as a hepatoprotector that bind directly to the toxic metabolite of paracetamol, thereby reducing the use of glutathione and quench free radicals, so that oxidative stress in the liver decreased and gluthathione levels increased, AST and ALT activity decreased.


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References


Agrawal, S., Dhiman, R. K. and Limdi, J. K. (2016) ‘Evaluation of abnormal liver function tests’, Postgraduate Medical Journal, pp. 223–234. doi: 10.1136/postgradmedj-2015-133715.

Ahmad, M. M., Rezk, N. A., Fawzy, A., and Sabry, M. (2019) ‘Protective effects of curcumin and silymarin against paracetamol induced hepatotoxicity in adult male albino rats’, Gene, 712, p. 143966. doi: 10.1016/j.gene.2019.143966.

Bayomy, N. A., Elshafey, S. H., Mosaed, M. M., and Hegazy, A. M. S. (2015) ‘Protective Effect of Curcumin versus N-acetylcystein on Acetaminophen Induced Hepatotoxicity in Adult Albino Rats’, Journal of Cytology & Histology, s3(2), pp. 1–8. doi: 10.4172/2157-7099.s3-018.

Brune, K., Renner, B. and Tiegs, G. (2015) ‘Acetaminophen/paracetamol: A history of errors, failures and false decisions’, European Journal of Pain (United Kingdom), pp. 953–965. doi: 10.1002/ejp.621.

Bunchorntavakul, C. and Reddy, K. R. (2018) ‘Acetaminophen (APAP or N-Acetyl-p-Aminophenol) and Acute Liver Failure’, Clinics in Liver Disease, pp. 325–346. doi: 10.1016/j.cld.2018.01.007.

Caparrotta, T. M., Antoine, D. J. and Dear, J. W. (2018) ‘Are some people at increased risk of paracetamol-induced liver injury? A critical review of the literature’, European Journal of Clinical Pharmacology, pp. 147–160. doi: 10.1007/s00228-017-2356-6.

El-Maddawy, Z. K. and El-Sayed, Y. S. (2018) ‘Comparative analysis of the protective effects of curcumin and N-acetyl cysteine against paracetamol-induced hepatic, renal, and testicular toxicity in Wistar rats’, Environmental Science and Pollution Research, 25(4), pp. 3468–3479. doi: 10.1007/s11356-017-0750-3.

Essawy, A., Alkhuriji, A. F. and Soffar, A. A. (2017) ‘Paracetamol overdose induces physiological and pathological aberrations in rat brain’, Journal of Applied Pharmaceutical Science, 7(9), pp. 185–190. doi: 10.7324/JAPS.2017.70925.

Fadil, H. A., Edress, N., Khorshid, N., Amin, N. (2019) ‘Protective Impact of Curcumin against Paracetamol-Induced Hepatotoxicity in Rats’, 8(1), pp. 84–94.

Farzaei, M. H., Zobeiri, M., Parvizi, F., El-Senduny, F. F., Marmouzi, I., Coy-Barrera, E., Naseri, R., Nabavi, S. M., Rahimi, R., Abdollahi, M. (2018) ‘Curcumin in liver diseases: A systematic review of the cellular mechanisms of oxidative stress and clinical perspective’, Nutrients, p. 855. doi: 10.3390/nu10070855.

Jayadi, T. and Widiasmoko, B. (2018) ‘Curcumin benefits as antioxidant, antiinflamation and antiapoptosis ameliorate paracetamol toxicity’, Asian Journal of Pharmaceutical and Clinical Research, 11(3), pp. 1–3. doi: 10.22159/ajpcr.2018.v11s3.29959.

Mazaleuskaya, L. L., Sangkuhl, K., Thorn, C. F., Fitzgerald, G. A., Altman, R. B., Klein, T. E. (2015) ‘PharmGKB summary: Pathways of acetaminophen metabolism at the therapeutic versus toxic doses’, Pharmacogenetics and Genomics, 25(8), pp. 416–426. doi: 10.1097/FPC.0000000000000150.

Mohanty, C. and Sahoo, S. K. (2017) ‘Curcumin and its topical formulations for wound healing applications’, Drug Discovery Today, pp. 1582–1592. doi: 10.1016/j.drudis.2017.07.001.

Nimse, S. B. and Pal, D. (2015) ‘Free radicals, natural antioxidants, and their reaction mechanisms’, RSC Advances, 5(35), pp. 27986–28006. doi: 10.1039/c4ra13315c.

Del Prado-Audelo, M. L., Caballero-Florán, I. H., Meza-Toledo, J. A., Mendoza-Muñoz, N., González-Torres, M., Florán, B., Cortés, H., Leyva-Gómez, G. (2019) ‘Formulations of curcumin nanoparticles for brain diseases’, Biomolecules, p. 56. doi: 10.3390/biom9020056.

Priyanka, R., Vasundhara, M. and Ah, M. R. (2019) ‘Chemo-profiling of Curcuma aromatica Salisbury rhizomes and leaves from South India’, 7(4), pp. 260–262.

Pulido-Moran, M., Moreno-Fernandez, J., Ramirez-Tortosa, C., Ramirez-Tortosa, M. C. (2016) ‘Curcumin and health’, Molecules, p. 264. doi: 10.3390/molecules21030264.

Rezania, V., Coombe, D. and Tuszynski, J. A. (2016) ‘A physiologically-based flow network model for hepatic drug elimination III: 2D/3D DLA lobule models’, Theoretical Biology and Medical Modelling, 13(9), pp. 1–22. doi: 10.1186/s12976-016-0034-5.

Sedky, R. A., Taha, N. M., Mandour, A. E. W., Lebda, M. A., Hashem, A. E. (2019) ‘Potential Protective Effect of Curcumin on Paracetamol Model of Liver Injury in Rats’, Alexandria Journal of Veterinary Sciences, 63(1), p. 77. doi: 10.5455/ajvs.63350.

Trefts, E., Gannon, M. and Wasserman, D. H. (2017) ‘The liver’, Current Biology, pp. 1147–1151. doi: 10.1016/j.cub.2017.09.019.

Vickers, A. E. M., Ulyanov, A. V. and Fisher, R. L. (2017) ‘Liver effects of clinical drugs differentiated in human liver slices’, International Journal of Molecular Sciences, 18(3), p. 574. doi: 10.3390/ijms18030574.

Wang, X., Wu, Q., Liu, A., Anadón, A., Rodríguez, J. L., Martínez-Larrañaga, M. R., Yuan, Z., Martínez, M. A. (2017) ‘Paracetamol: overdose-induced oxidative stress toxicity, metabolism, and protective effects of various compounds in vivo and in vitro’, Drug Metabolism Reviews, pp. 395–437. doi: 10.1080/03602532.2017.1354014.

Zahran, R. F., Geba, Z. M., Tabll, A. A., Mashaly, M. M. (2020) ‘Therapeutic potential of a novel combination of Curcumin with Sulfamethoxazole against carbon tetrachloride-induced acute liver injury in Swiss albino mice’, Journal of Genetic Engineering and Biotechnology, 18(1), p. 13. doi: 10.1186/s43141-020-00027-9.

Żur, J., Piński, A., Marchlewicz, A., Hupert-Kocurek, K., Wojcieszyńska, D., Guzik, U. (2018) ‘Organic micropollutants paracetamol and ibuprofen—toxicity, biodegradation, and genetic background of their utilization by bacteria’, Environmental Science and Pollution Research, pp. 21498–21524. doi: 10.1007/s11356-018-2517-x.




DOI: http://dx.doi.org/10.30742/jikw.v10i2.1250

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