Protective effects of thiamine pyrophosphate and cinnamon against oxidative liver damage induced by an isoniazid and rifampicin combination in rats.
Efectos protectores del pirofosfato de tiamina y la canela contra el daño hepático oxidativo inducido por la combinación de isoniazida y rifampicina en ratas.
Keywords:
isoniazid, rifampicin, thiamine pyrophosphate, cinnamon extract, oxidative stress, inflammation
Abstract
Isoniazid and rifampicin (IRC) have been shown to cause hepatotoxicity in both clinical and preclinical studies. Oxidative stress and inflammation have been held responsible for the pathogenesis of IRC-induced hepatotoxicity. Antioxidative and anti-inflammatory effects of thiamine pyrophosphate (TPP) and cinnamon extract (CE) have been shown in previous studies. Therefore, our study investigated the protective effects of TPP and CE on possible liver damage caused by IRC treatment in rats. Twenty-four albino Wistar rats were categorized into four groups: a healthy group (HG), an IRC group (IRG), a TPP+IRC group (TIRG), and a CE+IRC group (CIRG). TPP (25 mg/kg) was administered intraperitoneally to TIRG, while CE (100 mg/kg) was administered orally to CIRG. In IRG, TIRG, and CIRG, isoniazid (50 mg/kg) and rifampicin (50 mg/kg) were administered orally one hour after these treatments. For seven days, this procedure was repeated once a day. After this period, blood samples were taken from the tail veins, and the rats were sacrificed. The removed liver tissues were analyzed for oxidant, antioxidant, and proinflammatory cytokines and subjected to histopathological evaluation. Serum alanine aminotransferase and aspartate aminotransferase activities were also measured. An increase in malondialdehyde, nuclear factor kappa B, tumor necrosis factor-alpha, interleukin 1 beta, and interleukin-6 levels, a decrease in total glutathione levels, superoxide dismutase and catalase activities, and an increase in alanine aminotransferase and aspartate aminotrans-ferase activities were found with IRC treatment (p<0.001). The histopatho-logical analysis of the IRG suggested hepatotoxicity (p<0.001). TPP and CE administered with IRC inhibited the biochemical changes (p<0.001). In the TIRG, this inhibition was higher than in the CIRG (p<0.05). Histological damage was inhibited by TPP (p<0.001). CE prevented biochemical changes but not histological changes except inflammatory cell infiltration. Therefore, TPP may be better than CE in preventing IRC-induced hepatotoxicity.
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References
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Suárez I, Fünger SM, Kröger S, Rademacher J, Fätkenheuer G, Rybniker J. The diagnosis and treatment of tuberculosis. Dtsch Arztebl Int 2019;116:729-735.
Forget EJ, Menzies D. Adverse reactions to first-line antituberculosis drugs. Expert Opin Drug Saf 2006;5:231-249.
Yew WW, Chang KC, Chan DP. Oxidative stress and first-line antituberculosis drug-induced hepatotoxicity. Antimicrob Agents Chemother 2018;62:e02637-17
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Ahadpour M, Eskandari MR, Mashayekhi V, Haj Mohammad Ebrahim Tehrani K, Jafarian I, Naserzadeh P, Hosseini MJ. Mitochondrial oxidative stress and dysfunction induced by isoniazid: study on isolated rat liver and brain mitochondria. Drug Chem Toxicol 2016;39:224-232.
Shuhendler AJ, Pu K, Cui L, Uetrecht JP, Rao J. Real-time imaging of oxidative and nitrosative stress in the liver of live animals for drug-toxicity testing. Nat Biotechnol 2014;32:373-380.
Askgaard DS, Wilcke T, Døssing M. He patotoxicity caused by the combined action of isoniazid and rifampicin. Thorax 1995;50:213-214.
Sica DA. Loop diuretic therapy, thiamine balance, and heart failure. Congest Heart Fail 2007;13:244-247.
Altuner D, Cetin N, Suleyman B, Aslan Z, Hacimuftuoglu A, Gulaboglu M, Isaoglu N, I Demiryilmaz I, Suleyman H. Effect of thiamine pyrophosphate on ischemia-reperfusion induced oxidative damage in rat kidney. Indian J Pharmacol 2013;45:339-343.
Acun Delen L, Korkmaz Dişli Z, Taş HG, Kuyrukluyildiz U, Yazici GN, Süleyman B, Kuzucu M, Gürsu C, Suleyman H. The effects of thiamine pyrophosphate on propofol-induced oxidative liver injury and effect on dysfunction. Gen Physiol Biophys 2022;41:63-70.
Turan MI, Cayir A, Cetin N, Suleyman H, Siltelioglu Turan I, Tan H. An investigation of the effect of thiamine pyrophosphate on cisplatin-induced oxidative stress and DNA damage in rat brain tissue compared with thiamine: thiamine and thiamine pyrophosphate effects on cisplatin neuro-toxicity. Hum Exp Toxicol 2014;33:14-21.
Yanakiev S. Effects of cinnamon (Cinnamomum spp.) in dentistry: A review. Molecules 2020;25:4184.
Gruenwald J, Freder J, Armbruester N. Cinnamon and health. Crit Rev Food Sci Nutr 2010;50:822-834.
Dorri M, Hashemitabar S, Hosseinzadeh H. Cinnamon (Cinnamomum zeylanicum) as an antidote or a protective agent against natural or chemical toxicities: a review. Drug Chem Toxicol 2018;41:338-351.
Ho SC, Chang KS, Chang PW. Inhibition of neuroinflammation by cinnamon and its main components. Food Chem 2013;138:2275-2282.
Góth L. A simple method for determination of serum catalase activity and revision of reference range. Clin Chim Acta 1991;196(2-3):143-151.
Tostmann A, Boeree MJ, Aarnoutse RE, de Lange WC, van der Ven AJ, Dekhuijzen R. Antituberculosis drug-induced hepato-toxicity: concise up-todate review. J Gastroenterol Hepatol 2008;23(2):192-202.
Enriquez-Cortina C, Almonte-Becerril M, Clavijo-Cornejo D, Palestino-Domínguez M, Bello-Monroy O, Nuño N, López A, Bucio L, Souza V, Hernández-Pando R, Muñoz L, Gutiérrez-Ruiz MC, Gómez- Quiroz LE. Hepatocyte growth factor protects against isoniazid/rifampicin-induced oxidative liver damage. Toxicol Sci 2013;135:26-36.
Aynaoglu Yildiz G, Yapca OE, Dinc K, Gursul C, Gundogdu B, Aktas M, Suleyman Z, Bulut S, Suleyman H. Stress-associated ovarian damage, infertility, and delay in achieving pregnancy and treatment options. Invest Clin 2023;64:513-523. doi. org/10.54817/IC.v64n4a08
Zhuang X, Li L, Liu T, Zhang R, Yang P, Wang X, Dai L. Mechanisms of isoniazid and rifampicin-induced liver injury and the effects of natural medicinal ingredients: A review. Front Pharmacol 2022;13:1037814.
Pelapelapon AA, Rohmawaty E, Herman H. Evaluation of the hepatoprotective effect of Plantago major extract in a rifampicin-isoniazid induced hepatitis rat model. Trends in Sciences 2023;20:6331- 6331.
Sarandol E, Tas S, Serdar Z, Dirican M. Effects of thiamine treatment on oxidative stress in experimental diabetes. Bratislavske Lekarske Listy 2020;121:235-241.
Bedir Z, Erdem KTO, Can A, Çiçek B, Gülaboğlu M, Süleyman Z, Gürsul C, Mokhtare B, Özçiçek F, Süleyman H. Effect of thiamine pyrophosphate upon possible metamizole-induced liver injury in rats. Int J Pharmacol 2023;19:139-146.
Moselhy SS, Ali HK. Hepatoprotective effect of cinnamon extracts against carbon tetrachloride induced oxidative stress and liver injury in rats. Biol Res 2009;42:93-98.
Naji KM, Al-Khatib BY, Al-Haj NS, D’souza MR. Hepatoprotective activity of melittin on isoniazid-and rifampicin-induced liver injuries in male albino rats. BMC Pharmacol Toxicol 2021;22:1-11.
Zhang G, Zhu J, Zhou Y, Wei Y, Xi L, Qin H, Rao Z, Han M, Ma Y, Wu X. Hesperidin alleviates oxidative stress and upregulates the multidrug resistance protein 2 in isoniazid and rifampicin‐induced liver injury in rats. J Biochem Mol Toxicol 2016;30:342-349.
Sanjay S, Girish C, Toi PC, Bobby Z. Gallic acid attenuates isoniazid and rifampicin-induced liver injury by improving hepatic redox homeostasis through influence on Nrf2 and NF-κB signalling cascades in Wistar Rats. J Pharm Pharmacol 2021;73:473- 486.
El-Kholy M, Faried A, Ghada M. Role of cinnamon extract in the protection against amoxicillin/clavulanate-induced liver damage in rats. IOSR-JPBS. 2019;14:14- 21.
Kaya A, Ceylan AF, Kavutcu M, Santa-maria A, Šoltésová Prnová M, Stefek M, Karasu Ç. A dual-acting aldose reductase inhibitor impedes oxidative and carbonyl stress in tissues of fructose-and strep tozotocin-induced rats: comparison with antioxidant stobadine. Drug ChemToxicol 2023;5:1-11.
He X, Song Y, Wang L, Xu J. Protective effect of pyrrolidine dithiocarbamate on isoniazid/rifampicin‑induced liver injury in rats. Mol Med Rep 2020;21:463-469.
Yang J, Li G, Bao X, Suo Y, Xu H, Deng Y, Feng T, Deng G. Hepatoprotective effects of phloridzin against isoniazid-rifampicin induced liver injury by regulating CYP450 and Nrf2/HO-1 pathway in mice. Chem Pharm Bull 2022;70:805-811.
Wang N, Jiang D, Zhou C, Han X. Alpha-solanine inhibits endothelial inflammation via nuclear factor kappa B signaling pathway. Adv Clin Exp Med. 2023;32:909- 920.
Ozer M, Ince S, Gundogdu B, Aktas M, Uzel K, Gursul C, Suleyman H, Suleyman Z. Effect of thiamine pyrophosphate on cyclophosphamide-induced oxidative ovarian damage and reproductive dysfunction in female rats. Adv Clin Exp Med 2022;31:129-137.
Li B, Li J, Hu S. Cinnamon could improve hepatic steatosis caused by a high‐fat diet via enhancing hepatic beta‐oxidation and inhibiting hepatic lipogenesis, oxidative damage, and inflammation in male rats. J Food Biochem 2022;46:e14077.
Zhai H, Yang B, Fu Y, Zhang D, Li Y, Huang J. Effects of somatostatin in combination with early hemoperfusion on inflammatory, hemorheological and oxidative parameters during the treatment of acute pancreatitis. Invest Clín. 2023;64:41-52.
Wang Y, Che M, Xin J, Zheng Z, Li J, Zhang S. The role of IL -1β and TNF-α in intervertebral disc degeneration. Biomed Pharmacother 2020;131:110660.
Patel S, Chaturvedi A, Dubey N, Shrivastava A, Ganeshpurkar A. Ascorbic acid ameliorates isoniazid-rifampicin-induced hepatocellular damage in rats. iLIVER. 2022;1:72-77.
Ucak T, Karakurt Y, Tasli G, Cimen FK, Icel E, Kurt N, Ahiskali I, Süleyman H. The effects of thiamine pyrophosphate on ethanol induced optic nerve damage. BMC Pharmacol Toxicol 2019;20:40.
Kanuri G, Weber S, Volynets V, Spruss A, Bischoff SC, Bergheim I. Cinnamon extract protects against acute alcohol-induced liver steatosis in mice. J Nutr 2009;139:482-487.
Hussain S, Ashafaq M, Alshahrani S, Siddiqui R, Ahmed RA, Khuwaja G, Islam F. Cinnamon oil against acetaminophen-induced acute liver toxicity by attenuating inflammation, oxidative stress and apoptosis. Toxicol Rep 2020;7:1296-1304.
Yilmaz I, Demiryilmaz I, Turan M, Cetin N, Gul M, Süleyman H. The effects of thiamine and thiamine pyrophosphate on alcohol-induced hepatic damage biomarkers in rats. Eur Rev Med Pharmacol Sci 2015;19:664-670.
Uysal HB, Dağlı B, Yılmaz M, Kahyaoğlu F, Gökçimen A, Ömürlü İK, Demirci B. Biochemical and histological effects of thiamine pyrophosphate against acetaminophen‐induced hepatotoxicity. Basic Clin Pharmacol Toxicol 2016;118:70-76.
Eidi A, Mortazavi P, Bazargan M, Zaringhalam J. Hepatoprotective activity of cinnamon ethanolic extract against CCI4- induced liver injury in rats. Excli Journal. 2012;11:495.
Suárez I, Fünger SM, Kröger S, Rademacher J, Fätkenheuer G, Rybniker J. The diagnosis and treatment of tuberculosis. Dtsch Arztebl Int 2019;116:729-735.
Forget EJ, Menzies D. Adverse reactions to first-line antituberculosis drugs. Expert Opin Drug Saf 2006;5:231-249.
Yew WW, Chang KC, Chan DP. Oxidative stress and first-line antituberculosis drug-induced hepatotoxicity. Antimicrob Agents Chemother 2018;62:e02637-17
Song L, Zhang ZR, Zhang JL, Zhu XB, He L, Shi Z, Gao L, Li Y, Hu B, Feng FM. MicroRNA-122 is involved in oxidative stress in isoniazid-induced liver injury in mice. Genet Mol Res 2015;14:13258-13265.
Ahadpour M, Eskandari MR, Mashayekhi V, Haj Mohammad Ebrahim Tehrani K, Jafarian I, Naserzadeh P, Hosseini MJ. Mitochondrial oxidative stress and dysfunction induced by isoniazid: study on isolated rat liver and brain mitochondria. Drug Chem Toxicol 2016;39:224-232.
Shuhendler AJ, Pu K, Cui L, Uetrecht JP, Rao J. Real-time imaging of oxidative and nitrosative stress in the liver of live animals for drug-toxicity testing. Nat Biotechnol 2014;32:373-380.
Askgaard DS, Wilcke T, Døssing M. He patotoxicity caused by the combined action of isoniazid and rifampicin. Thorax 1995;50:213-214.
Sica DA. Loop diuretic therapy, thiamine balance, and heart failure. Congest Heart Fail 2007;13:244-247.
Altuner D, Cetin N, Suleyman B, Aslan Z, Hacimuftuoglu A, Gulaboglu M, Isaoglu N, I Demiryilmaz I, Suleyman H. Effect of thiamine pyrophosphate on ischemia-reperfusion induced oxidative damage in rat kidney. Indian J Pharmacol 2013;45:339-343.
Acun Delen L, Korkmaz Dişli Z, Taş HG, Kuyrukluyildiz U, Yazici GN, Süleyman B, Kuzucu M, Gürsu C, Suleyman H. The effects of thiamine pyrophosphate on propofol-induced oxidative liver injury and effect on dysfunction. Gen Physiol Biophys 2022;41:63-70.
Turan MI, Cayir A, Cetin N, Suleyman H, Siltelioglu Turan I, Tan H. An investigation of the effect of thiamine pyrophosphate on cisplatin-induced oxidative stress and DNA damage in rat brain tissue compared with thiamine: thiamine and thiamine pyrophosphate effects on cisplatin neuro-toxicity. Hum Exp Toxicol 2014;33:14-21.
Yanakiev S. Effects of cinnamon (Cinnamomum spp.) in dentistry: A review. Molecules 2020;25:4184.
Gruenwald J, Freder J, Armbruester N. Cinnamon and health. Crit Rev Food Sci Nutr 2010;50:822-834.
Dorri M, Hashemitabar S, Hosseinzadeh H. Cinnamon (Cinnamomum zeylanicum) as an antidote or a protective agent against natural or chemical toxicities: a review. Drug Chem Toxicol 2018;41:338-351.
Ho SC, Chang KS, Chang PW. Inhibition of neuroinflammation by cinnamon and its main components. Food Chem 2013;138:2275-2282.
Góth L. A simple method for determination of serum catalase activity and revision of reference range. Clin Chim Acta 1991;196(2-3):143-151.
Tostmann A, Boeree MJ, Aarnoutse RE, de Lange WC, van der Ven AJ, Dekhuijzen R. Antituberculosis drug-induced hepato-toxicity: concise up-todate review. J Gastroenterol Hepatol 2008;23(2):192-202.
Enriquez-Cortina C, Almonte-Becerril M, Clavijo-Cornejo D, Palestino-Domínguez M, Bello-Monroy O, Nuño N, López A, Bucio L, Souza V, Hernández-Pando R, Muñoz L, Gutiérrez-Ruiz MC, Gómez- Quiroz LE. Hepatocyte growth factor protects against isoniazid/rifampicin-induced oxidative liver damage. Toxicol Sci 2013;135:26-36.
Aynaoglu Yildiz G, Yapca OE, Dinc K, Gursul C, Gundogdu B, Aktas M, Suleyman Z, Bulut S, Suleyman H. Stress-associated ovarian damage, infertility, and delay in achieving pregnancy and treatment options. Invest Clin 2023;64:513-523. doi. org/10.54817/IC.v64n4a08
Zhuang X, Li L, Liu T, Zhang R, Yang P, Wang X, Dai L. Mechanisms of isoniazid and rifampicin-induced liver injury and the effects of natural medicinal ingredients: A review. Front Pharmacol 2022;13:1037814.
Pelapelapon AA, Rohmawaty E, Herman H. Evaluation of the hepatoprotective effect of Plantago major extract in a rifampicin-isoniazid induced hepatitis rat model. Trends in Sciences 2023;20:6331- 6331.
Sarandol E, Tas S, Serdar Z, Dirican M. Effects of thiamine treatment on oxidative stress in experimental diabetes. Bratislavske Lekarske Listy 2020;121:235-241.
Bedir Z, Erdem KTO, Can A, Çiçek B, Gülaboğlu M, Süleyman Z, Gürsul C, Mokhtare B, Özçiçek F, Süleyman H. Effect of thiamine pyrophosphate upon possible metamizole-induced liver injury in rats. Int J Pharmacol 2023;19:139-146.
Moselhy SS, Ali HK. Hepatoprotective effect of cinnamon extracts against carbon tetrachloride induced oxidative stress and liver injury in rats. Biol Res 2009;42:93-98.
Naji KM, Al-Khatib BY, Al-Haj NS, D’souza MR. Hepatoprotective activity of melittin on isoniazid-and rifampicin-induced liver injuries in male albino rats. BMC Pharmacol Toxicol 2021;22:1-11.
Zhang G, Zhu J, Zhou Y, Wei Y, Xi L, Qin H, Rao Z, Han M, Ma Y, Wu X. Hesperidin alleviates oxidative stress and upregulates the multidrug resistance protein 2 in isoniazid and rifampicin‐induced liver injury in rats. J Biochem Mol Toxicol 2016;30:342-349.
Sanjay S, Girish C, Toi PC, Bobby Z. Gallic acid attenuates isoniazid and rifampicin-induced liver injury by improving hepatic redox homeostasis through influence on Nrf2 and NF-κB signalling cascades in Wistar Rats. J Pharm Pharmacol 2021;73:473- 486.
El-Kholy M, Faried A, Ghada M. Role of cinnamon extract in the protection against amoxicillin/clavulanate-induced liver damage in rats. IOSR-JPBS. 2019;14:14- 21.
Kaya A, Ceylan AF, Kavutcu M, Santa-maria A, Šoltésová Prnová M, Stefek M, Karasu Ç. A dual-acting aldose reductase inhibitor impedes oxidative and carbonyl stress in tissues of fructose-and strep tozotocin-induced rats: comparison with antioxidant stobadine. Drug ChemToxicol 2023;5:1-11.
He X, Song Y, Wang L, Xu J. Protective effect of pyrrolidine dithiocarbamate on isoniazid/rifampicin‑induced liver injury in rats. Mol Med Rep 2020;21:463-469.
Yang J, Li G, Bao X, Suo Y, Xu H, Deng Y, Feng T, Deng G. Hepatoprotective effects of phloridzin against isoniazid-rifampicin induced liver injury by regulating CYP450 and Nrf2/HO-1 pathway in mice. Chem Pharm Bull 2022;70:805-811.
Wang N, Jiang D, Zhou C, Han X. Alpha-solanine inhibits endothelial inflammation via nuclear factor kappa B signaling pathway. Adv Clin Exp Med. 2023;32:909- 920.
Ozer M, Ince S, Gundogdu B, Aktas M, Uzel K, Gursul C, Suleyman H, Suleyman Z. Effect of thiamine pyrophosphate on cyclophosphamide-induced oxidative ovarian damage and reproductive dysfunction in female rats. Adv Clin Exp Med 2022;31:129-137.
Li B, Li J, Hu S. Cinnamon could improve hepatic steatosis caused by a high‐fat diet via enhancing hepatic beta‐oxidation and inhibiting hepatic lipogenesis, oxidative damage, and inflammation in male rats. J Food Biochem 2022;46:e14077.
Zhai H, Yang B, Fu Y, Zhang D, Li Y, Huang J. Effects of somatostatin in combination with early hemoperfusion on inflammatory, hemorheological and oxidative parameters during the treatment of acute pancreatitis. Invest Clín. 2023;64:41-52.
Wang Y, Che M, Xin J, Zheng Z, Li J, Zhang S. The role of IL -1β and TNF-α in intervertebral disc degeneration. Biomed Pharmacother 2020;131:110660.
Patel S, Chaturvedi A, Dubey N, Shrivastava A, Ganeshpurkar A. Ascorbic acid ameliorates isoniazid-rifampicin-induced hepatocellular damage in rats. iLIVER. 2022;1:72-77.
Ucak T, Karakurt Y, Tasli G, Cimen FK, Icel E, Kurt N, Ahiskali I, Süleyman H. The effects of thiamine pyrophosphate on ethanol induced optic nerve damage. BMC Pharmacol Toxicol 2019;20:40.
Kanuri G, Weber S, Volynets V, Spruss A, Bischoff SC, Bergheim I. Cinnamon extract protects against acute alcohol-induced liver steatosis in mice. J Nutr 2009;139:482-487.
Hussain S, Ashafaq M, Alshahrani S, Siddiqui R, Ahmed RA, Khuwaja G, Islam F. Cinnamon oil against acetaminophen-induced acute liver toxicity by attenuating inflammation, oxidative stress and apoptosis. Toxicol Rep 2020;7:1296-1304.
Yilmaz I, Demiryilmaz I, Turan M, Cetin N, Gul M, Süleyman H. The effects of thiamine and thiamine pyrophosphate on alcohol-induced hepatic damage biomarkers in rats. Eur Rev Med Pharmacol Sci 2015;19:664-670.
Uysal HB, Dağlı B, Yılmaz M, Kahyaoğlu F, Gökçimen A, Ömürlü İK, Demirci B. Biochemical and histological effects of thiamine pyrophosphate against acetaminophen‐induced hepatotoxicity. Basic Clin Pharmacol Toxicol 2016;118:70-76.
Eidi A, Mortazavi P, Bazargan M, Zaringhalam J. Hepatoprotective activity of cinnamon ethanolic extract against CCI4- induced liver injury in rats. Excli Journal. 2012;11:495.
Published
2024-08-20
How to Cite
Yeter, B., Mammadov, R., Koc, Z., Bulut, S., Tastan, T. B., Gulaboglu, M., & Suleyman, H. (2024). Protective effects of thiamine pyrophosphate and cinnamon against oxidative liver damage induced by an isoniazid and rifampicin combination in rats.: Efectos protectores del pirofosfato de tiamina y la canela contra el daño hepático oxidativo inducido por la combinación de isoniazida y rifampicina en ratas. Investigación Clínica, 65(3), 321-334. https://doi.org/10.54817/IC.v65n3a05
Section
Original Works
