Protective Effects of Ferulic Acid Against Isoniazid-
Induced Hepatotoxicity in Rats

Anani, Hossein; Karami-Mohajeri, Somayyeh; Sharififar, Fariba; ahmadipour, ahmad

Protective Effects of Ferulic Acid Against Isoniazid- Induced Hepatotoxicity in Rats

Ahmad AHMADIPOUR, (Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran)

Fariba SHARIFIFAR, (Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran)

Hussein ANANI, (Faculty of Allied Medical Sciences, Kerman University of Medical Sciences, Kerman, Iran)

Somayyeh KARAMI-MOHAJERI (Department of Pharmacology and Toxicology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran)

FABAD Journal of Pharmaceutical Sciences

32 9

Yıl: 2021 Cilt: 46 Sayı: 2 Sayfa Aralığı: 119 - 128 Metin Dili: İngilizce İndeks Tarihi: 29-05-2022

Protective Effects of Ferulic Acid Against Isoniazid- Induced Hepatotoxicity in Rats

Öz:

Isoniazid (INH) is an antibiotic that is used for the prevention and treatment of tuberculosis. The most common side effect of INH is seemingly hepatotoxicity through the induction of oxidative damage. Ferulic acid (FA) is an organic compound with antioxidant properties that is found abundantly in plant cell walls. The aim of this study was to evaluate the hepatoprotective effects of FA against hepatotoxicity induced by INH in Wistar rats. The rats were injected with INH (100 mg/kg/d for 21 days) with and without co-administration of FA (10 and 20 mg/kg/d) or silymarin (100 mg/kg/d) from day 11 to day 21. Then, the animals were sacrificed to evaluate the serum level of aminotransferases and total bilirubin, and liver histopathology and oxidative stress parameters. Co-administration of FA prevented the hepatotoxicity of INH according to the biochemical and histology findings. FA dose-dependently decreased level of lipid peroxidation in liver tissue. The activities of catalase, superoxide dismutase, and glutathione peroxidase in liver tissues of rats treated with FA were higher than those in non-treated INH-exposed rats. Taken together, the results demonstrated that FA could be used as a hepatoprotective supplement to prevent INH-induced hepatotoxicity

Anahtar Kelime:

Ferulik Asidin Sıçanlarda İzoniazidle İndüklenen Hepatotoksisiteye Karşı Koruyucu Etkileri

Öz:

İzoniazid (INH), tüberkülozun önlenmesi ve tedavisinde kullanılan bir antibiyotiktir. INH’nin en yaygın yan etkisi, oksidatif hasarın indüksiyonu yoluyla görülen hepatotoksisitedir. Ferulik asit (FA), bitki hücre duvarlarında bol miktarda bulunan antioksidan özelliklere sahip organik bir bileşiktir. Bu çalışmanın amacı, FA’nın Wistar sıçanlarda INH’nin neden olduğu hepatotoksisiteye karşı hepatoprotektif etkilerini değerlendirmektir. Sıçanlara, 11. günden 21. güne kadar sadece INH (21 gün boyunca 100 mg / kg / gün) ya da INH ile birlikte FA (10 ve 20 mg / kg / gün) veya silimarin (100 mg / kg / gün) enjekte edilmiştir. Daha sonra hayvanlar, serum aminotransferazlar ile total bilirubinin seviyesini, karaciğer histopatolojisini ve oksidatif stres parametrelerini değerlendirmek için ötanazi edilmiştir. Biyokimya ve histoloji bulgularına göre FA’nın birlikte uygulanması INH’nin hepatotoksisitesini önlemiştir. FA, doza bağlı olarak karaciğer dokusunda lipid peroksidasyon seviyesini düşürmüştür. FA uygulanan sıçanların karaciğer dokularındaki katalaz, süperoksit dismutaz ve glutatyon peroksidaz aktiviteleri, FA uygulanmayan INH’ye maruz kalan sıçanlara göre daha yüksek bulunmuştur. Birlikte ele alındığında sonuçlar, FA’nın INH’nin neden olduğu hepatotoksisiteyi önlemek için hepatoprotektif bir destek olarak kullanılabileceğini göstermiştir.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

Baradaran, A., Samadi, F., Ramezanpour, S. S., Yousefdoust, S. (2019). Hepatoprotective effects of silymarin on CCl4-induced hepatic damage in broiler chickens model. Toxicology Reports, 6, 788- 794. doi:10.1016/j.toxrep.2019.07.011
Bhadauria, S., Singh, G., Sinha, N., Srivastava, S. (2007). Isoniazid induces oxidative stress, mitochondrial dysfunction and apoptosis in Hep G2 cells. Cellular and Molecular Biology (Noisy-legrand), 53(1), 102-114.
Bhilare, N. V., Dhaneshwar, S. S., Mahadik, K. R., Dasgupta, A. (2020). Co-drug of isoniazid and sulfur containing antioxidant for attenuation of hepatotoxicity and treatment of tuberculosis. Drug and Chemical Toxicology, 1-11. doi:10.1080 /01480545.2020.1778021
Bumrungpert, A., Lilitchan, S., Tuntipopipat, S., Tirawanchai, N., Komindr, S. (2018). Ferulic acid supplementation improves lipid profiles, oxidative stress, and inflammatory status in hyperlipidemic subjects: a randomized, double-blind, placebo-controlled clinical trial. Nutrients, 10(6). doi:10.3390/nu10060713
Chang, T. E., Huang, Y. S., Chang, C. H., Perng, C. L., Huang, Y. H., Hou, M. C. (2018). The susceptibility of anti-tuberculosis drug-induced liver injury and chronic hepatitis C infection: A systematic review and meta-analysis. Journal of the Chinese Medical Association, 81(2), 111-118. doi:10.1016/j. jcma.2017.10.002
Dong, W. G., Liu, S. P., Yu, B. P., Wu, D. F., Luo, H. S., Yu, J. P. (2003). Ameliorative effects of sodium ferulate on experimental colitis and their mechanisms in rats. World Journal of Gastroenterology, 9(11), 2533-2538. doi:10.3748/wjg.v9.i11.2533
Gerin, F., Erman, H., Erboga, M., Sener, U., Yilmaz, A., Seyhan, H., Gurel, A. (2016). The effects of ferulic acid against oxidative stress and inflammation in formaldehyde-Induced hepatotoxicity. Inflammation, 39(4), 1377-1386. doi:10.1007/ s10753-016-0369-4
Goodman, Z. D. (2007). Grading and staging systems for inflammation and fibrosis in chronic liver diseases. Journal of Hepatology, 47(4), 598-607. doi:10.1016/j.jhep.2007.07.006
Graf, E. (1992). Antioxidant potential of ferulic acid. Free Radical Biology and Medicine , 13(4), 435-448. Harder, H., Tetens, I., Let, M. B., Meyer, A. S. (2004). Rye bran bread intake elevates urinary excretion of ferulic acid in humans, but does not affect the susceptibility of LDL to oxidation ex vivo. European Journal of Nutrition, 43(4), 230-236. doi:10.1007/ s00394-004-0463-5
Hassan, H. M., Guo, H. L., Yousef, B. A., Luyong, Z., Zhenzhou, J. (2015). Hepatotoxicity mechanisms of isoniazid: A mini-review. Journal of Applied Toxicology, 35(12), 1427-1432. doi:10.1002/ jat.3175
Hassan, H. M., Guo, H., Yousef, B. A., Guerram, M., Hamdi, A. M., Zhang, L., Jiang, Z. (2016). Role of inflammatory and oxidative stress, cytochrome P450 2E1, and bile acid disturbance in rat liver injury induced by isoniazid and lipopolysaccharide cotreatment. Antimicrobial Agents and Chemotherapy, 60(9), 5285-5293. doi:10.1128/AAC.00854-16
Jia, Z. L., Cen, J., Wang, J. B., Zhang, F., Xia, Q., Wang, X., ... Zhang, Y. (2019). Mechanism of isoniazid- induced hepatotoxicity in zebrafish larvae: Activation of ROS-mediated ERS, apoptosis and the Nrf2 pathway. Chemosphere, 227, 541-550. doi:10.1016/j.chemosphere.2019.04.026
Joshi, G., Perluigi, M., Sultana, R., Agrippino, R., Calabrese, V., Butterfield, D. A. (2006). In vivo protection of synaptosomes by ferulic acid ethyl ester (FAEE) from oxidative stress mediated by 2,2-azobis(2-amidino-propane)dihydrochloride (AAPH) or Fe(2+)/H(2)O(2): Insight into mechanisms of neuroprotection and relevance to oxidative stress-related neurodegenerative disorders. Neurochemistry International, 48(4), 318-327. doi:10.1016/j.neuint.2005.11.006
Kanski, J., Aksenova, M., Stoyanova, A., Butterfield, D. A. (2002). Ferulic acid antioxidant protection against hydroxyl and peroxyl radical oxidation in synaptosomal and neuronal cell culture systems in vitro: structure-activity studies. Journal of Nutritional Biochemistry, 13(5), 273-281.
Kargar Jahromi, H., Pourahmad, M., Abedi, H. A., Karimi, M., Kargar Jahromi, Z. (2018). Protective effects of salep against isoniazid liver toxicity in wistar rats. Journal of Traditional and Complementary Medicine, 8(1), 239-243. doi:10.1016/j. jtcme.2017.06.001
Kimura, T., Hayashida, H., Murata, M., Takamatsu, J. (2011). Effect of ferulic acid and Angelica archangelica extract on behavioral and psychological symptoms of dementia in frontotemporal lobar degeneration and dementia with Lewy bodies. Geriatrics & Gerontology International, 11(3), 309- 314. doi:10.1111/j.1447-0594.2010.00687.x
Kumar, S., Kumar, R., Dwivedi, A., Pandey, A. K. (2014). In vitro antioxidant, antibacterial, and cytotoxic activity and in vivo effect of Syngonium podophyllum and Eichhornia crassipes leaf extracts on isoniazid induced oxidative stress and hepatic markers. BioMed Research International, 2014, 459452. doi:10.1155/2014/459452
Mancuso, C., Santangelo, R. (2014). Ferulic acid: Pharmacological and toxicological aspects. Food and Chemical Toxicology, 65, 185-195. doi:10.1016/j.fct.2013.12.024
Mathew, S., Abraham, T. E. (2004). Ferulic acid: An antioxidant found naturally in plant cell walls and feruloyl esterases involved in its release and their applications. Critical Reviews in Biotechnology, 24(2-3), 59-83. doi:10.1080/07388550490491467
Metushi, I. G., Sanders, C., Acute Liver Study, G., Lee, W. M., Uetrecht, J. (2014). Detection of anti-isoniazid and anti-cytochrome P450 antibodies in patients with isoniazid-induced liver failure. Hepatology, 59(3), 1084-1093. doi:10.1002/hep.26564
Murray, J. C., Burch, J. A., Streilein, R. D., Iannacchione, M. A., Hall, R. P., Pinnell, S. R. (2008). A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation. The Journal of the American Academy of Dermatology, 59(3), 418-425. doi:10.1016/j. jaad.2008.05.004
Niu, C., Sheng, Y., Zhu, E., Ji, L., Wang, Z. (2016). Ferulic acid prevents liver injury induced by Diosbulbin B and its mechanism. BioScience Trends, 10(5), 386-391. doi:10.5582/bst.2016.01152 Noble, J. E., Bailey, M. J. (2009). Quantitation of protein. Methods in Enzymology, 463, 73-95. doi:10.1016/s0076-6879(09)63008-1
Paglia, D. E., Valentine, W. N. (1967). Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. Journal of Laboratory and Clinical Medicine, 70(1), 158-169. Pal, S. K., Shukla, Y. (2003). Herbal medicine: Current status and the future. Asian Pacific Journal of Cancer Prevention, 4(4), 281-288.
Palanisamy, N., Manian, S. (2012). Protective effects of Asparagus racemosus on oxidative damage in isoniazid-induced hepatotoxic rats: An in vivo study. Toxicology & Industrial Health, 28(3), 238- 244. doi:10.1177/0748233711410911
Prakash, D., Upadhyay, G., Pushpangadan, P., Gupta, C. (2011). Antioxidant and free radical scavenging activities of some fruits. Journal of Complementary and Integrative Medicine, 8. doi:10.2202/1553- 3840.1513
Raghu, R., Karthikeyan, S. (2016). Zidovudine and isoniazid induced liver toxicity and oxidative stress: Evaluation of mitigating properties of silibinin. Environmental Toxicology and Pharmacology, 46, 217-226. doi:10.1016/j.etap.2016.07.014
Ramappa, V., Aithal, G. P. (2013). Hepatotoxicity related to anti-tuberculosis drugs: Mechanisms and management. Journal of Clinical and Experimental Hepatology, 3(1), 37-49. doi:10.1016/j. jceh.2012.12.001
Roghani, M., Kalantari, H., Khodayar, M. J., Khorsandi, L., Kalantar, M., Goudarzi, M., Kalantar, H. (2020). Alleviation of liver dysfunction, oxidative stress and inflammation underlies the protective effect of ferulic acid in methotrexate-induced hepatotoxicity. Drug Design, Development and Therapy, 14, 1933-1941. doi:10.2147/DDDT.S237107
Rukkumani, R., Aruna, K., Suresh Varma, P., Padmanabhan Menon, V. (2004a). Hepatoprotective role of ferulic acid: A dose-dependent study. Journal of Medicinal Food , 7(4), 456-461. doi:10.1089/ jmf.2004.7.456
Rukkumani, R., Aruna, K., Varma, P. S., Menon, V. P. (2004b). Influence of ferulic acid on circulatory prooxidant-antioxidant status during alcohol and PUFA induced toxicity. Journal of Physiology and Pharmacology, 55(3), 551-561.
Sankar, M., Rajkumar, J., Sridhar, D. (2015). Hepatoprotective activity of heptoplus on isoniazid and rifampicin induced liver damage in rats. IIndian Journal of Pharmaceutical Sciences, 77(5), 556- 562. doi:10.4103/0250-474x.169028
Sodhi, C. P., Rana, S. F., Attri, S., Mehta, S., Yaiphei, K., Mehta, S. K. (1998). Oxidative-hepatic injury of isoniazid-rifampicin in young rats subjected to protein and energy malnutrition. Drug and Chemical Toxicology, 21(3), 305-317. doi:10.3109/01480549809002207
Sodhi, C. P., Rana, S. V., Mehta, S. K., Vaiphei, K., Attari, S., Mehta, S. (1997). Study of oxidative-stress in isoniazid-rifampicin induced hepatic injury in young rats. Drug Chem Toxicol, 20(3), 255-269. doi:10.3109/01480549709003881
Srinivasan, M., Sudheer, A. R., Menon, V. P. (2007). Ferulic Acid: therapeutic potential through its antioxidant property. Journal of Clinical Biochemistry and Nutrition, 40(2), 92-100. doi:10.3164/ jcbn.40.92
Sudheer, A. R., Chandran, K., Marimuthu, S., Menon, V. P. (2005). Ferulic Acid modulates altered lipid profiles and prooxidant/antioxidant status in circulation during nicotine-induced toxicity: A dose-dependent study. Toxicology Mechanisms and Methods, 15(6), 375-381. doi:10.1080/15376520500194783
Sun, Y., Oberley, L. W., Li, Y. (1988). A simple method for clinical assay of superoxide dismutase. Clinical Chemistry, 34(3), 497-500.
Tasduq, S. A., Kaiser, P., Sharma, S. C., 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. Hepatology Research, 37(10), 845-853. doi:10.1111/j.1872-034X.2007.00129.x
Tonomura, Y., Kato, Y., Hanafusa, H., Morikawa, Y., Matsuyama, K., Uehara, T., ... Torii, M. (2015). Diagnostic and predictive performance and standardized threshold of traditional biomarkers for drug-induced liver injury in rats. Journal of Applied Toxicology, 35(2), 165-172. doi:10.1002/jat.3053
Trombino, S., Cassano, R., Ferrarelli, T., Barone, E., Picci, N., Mancuso, C. (2013). Trans-ferulic acid- based solid lipid nanoparticles and their antioxidant effect in rat brain microsomes. Colloids Surf B Biointerfaces, 109, 273-279. doi:10.1016/j. colsurfb.2013.04.005
Viswanatha Swamy, A. H., Kulkarni, R. V., Thippeswamy, A. H., Koti, B. C., Gore, A. (2010). Evaluation of hepatoprotective activity of Cissus quadrangularis stem extract against isoniazid-induced liver damage in rats. Indian Journal of Pharmacology, 42(6), 397-400. doi:10.4103/0253-7613.71920
Wang, J. M., Sheng, Y. C., Ji, L. L., Wang, Z. T. (2014). Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo. Journal of Zheijang University SCIENCE B, 15(6), 540-547. doi:10.1631/jzus.B1300250
Wang, J. Y., Burger, R. M., Drlica, K. (1998). Role of superoxide in catalase-peroxidase-mediated isoniazid action against mycobacteria. Antimicrobial Agents and Chemotherapy, 42(3), 709-711.
Wasowicz, W., Neve, J., Peretz, A. (1993). Optimized steps in fluorometric determination of thiobarbituric acid-reactive substances in serum: importance of extraction pH and influence of sample preservation and storage. Clinical Chemistry, 39(12), 2522-2526.
Yang, Y., Jiang, L., Wang, S., Zeng, T., Xie, K. (2016). Diallyl trisulfide protects the liver against hepatotoxicity induced by isoniazid and rifampin in mice by reducing oxidative stress and activating Kupffer cells. Toxicological Research (Camb), 5(3), 954-962. doi:10.1039/c5tx00440c
Yew, W. W., Chang, K. C., Chan, D. P. (2018). Oxidative stress and first-line antituberculosis drug-induced hepatotoxicity. Antimicrobial Agents and Chemotherapy , 62(8), e02637-02617. doi:10.1128/ aac.02637-17
Yu, Y. C., Mao, Y. M., Chen, C. W., Chen, J. J., Chen, J., Cong, W. M., . . . Chinese Medical, A. (2017). CSH guidelines for the diagnosis and treatment of drug-induced liver injury. Hepatology International, 11(3), 221-241. doi:10.1007/s12072-017-9793-2
Yuan, J., Ge, K., Mu, J., Rong, J., Zhang, L., Wang, B., . . . Xia, G. (2016). Ferulic acid attenuated acetaminophen- induced hepatotoxicity though down-regulating the cytochrome P 2E1 and inhibiting tolllike receptor 4 signaling-mediated inflammation in mice. American Journal of Translational Research, 8(10), 4205-4214.
Yue, J., Dong, G., He, C., Chen, J., Liu, Y., Peng, R. (2009b). Protective effects of thiopronin against isoniazid-induced hepatotoxicity in rats. Toxicology, 264(3), 185-191. doi:10.1016/j.tox.2009.08.006 Yue, J., Peng, R. X., Yang, J., Kong, R., Liu, J. (2004). CYP2E1 mediated isoniazid-induced hepatotoxicity in rats. Acta Pharmaceutica Sinica, 25(5), 699-704.
Yue, J., Peng, R., Chen, J., Liu, Y., Dong, G. (2009a). Effects of rifampin on CYP2E1-dependent hepatotoxicity of isoniazid in rats. Pharmacological Research, 59(2), 112-119. doi:10.1016/j. phrs.2008.10.006
Zhao, Z., Moghadasian, M. H. (2008). Chemistry, natural sources, dietary intake and pharmacokinetic properties of ferulic acid: A review. Food Chemistry, 109(4), 691-702. doi:10.1016/j.foodchem. 2008.02.039

APA	ahmadipour a, Sharififar F, Anani H, Karami-Mohajeri S (2021). Protective Effects of Ferulic Acid Against Isoniazid- Induced Hepatotoxicity in Rats. , 119 - 128.
Chicago	ahmadipour ahmad,Sharififar Fariba,Anani Hossein,Karami-Mohajeri Somayyeh Protective Effects of Ferulic Acid Against Isoniazid- Induced Hepatotoxicity in Rats. (2021): 119 - 128.
MLA	ahmadipour ahmad,Sharififar Fariba,Anani Hossein,Karami-Mohajeri Somayyeh Protective Effects of Ferulic Acid Against Isoniazid- Induced Hepatotoxicity in Rats. , 2021, ss.119 - 128.
AMA	ahmadipour a,Sharififar F,Anani H,Karami-Mohajeri S Protective Effects of Ferulic Acid Against Isoniazid- Induced Hepatotoxicity in Rats. . 2021; 119 - 128.
Vancouver	ahmadipour a,Sharififar F,Anani H,Karami-Mohajeri S Protective Effects of Ferulic Acid Against Isoniazid- Induced Hepatotoxicity in Rats. . 2021; 119 - 128.
IEEE	ahmadipour a,Sharififar F,Anani H,Karami-Mohajeri S "Protective Effects of Ferulic Acid Against Isoniazid- Induced Hepatotoxicity in Rats." , ss.119 - 128, 2021.
ISNAD	ahmadipour, ahmad vd. "Protective Effects of Ferulic Acid Against Isoniazid- Induced Hepatotoxicity in Rats". (2021), 119-128.

APA	ahmadipour a, Sharififar F, Anani H, Karami-Mohajeri S (2021). Protective Effects of Ferulic Acid Against Isoniazid- Induced Hepatotoxicity in Rats. FABAD Journal of Pharmaceutical Sciences, 46(2), 119 - 128.
Chicago	ahmadipour ahmad,Sharififar Fariba,Anani Hossein,Karami-Mohajeri Somayyeh Protective Effects of Ferulic Acid Against Isoniazid- Induced Hepatotoxicity in Rats. FABAD Journal of Pharmaceutical Sciences 46, no.2 (2021): 119 - 128.
MLA	ahmadipour ahmad,Sharififar Fariba,Anani Hossein,Karami-Mohajeri Somayyeh Protective Effects of Ferulic Acid Against Isoniazid- Induced Hepatotoxicity in Rats. FABAD Journal of Pharmaceutical Sciences, vol.46, no.2, 2021, ss.119 - 128.
AMA	ahmadipour a,Sharififar F,Anani H,Karami-Mohajeri S Protective Effects of Ferulic Acid Against Isoniazid- Induced Hepatotoxicity in Rats. FABAD Journal of Pharmaceutical Sciences. 2021; 46(2): 119 - 128.
Vancouver	ahmadipour a,Sharififar F,Anani H,Karami-Mohajeri S Protective Effects of Ferulic Acid Against Isoniazid- Induced Hepatotoxicity in Rats. FABAD Journal of Pharmaceutical Sciences. 2021; 46(2): 119 - 128.
IEEE	ahmadipour a,Sharififar F,Anani H,Karami-Mohajeri S "Protective Effects of Ferulic Acid Against Isoniazid- Induced Hepatotoxicity in Rats." FABAD Journal of Pharmaceutical Sciences, 46, ss.119 - 128, 2021.
ISNAD	ahmadipour, ahmad vd. "Protective Effects of Ferulic Acid Against Isoniazid- Induced Hepatotoxicity in Rats". FABAD Journal of Pharmaceutical Sciences 46/2 (2021), 119-128.