Hepatoprotective Effect of Spondias pinnata in Isoniazid-Rifampicin-Induced Toxicity in Wistar rats
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Abstract
Anti-tubercular (TB) drugs can cause oxidative stress, leading to hepatotoxicity. Plant extracts have antioxidant effects that can reduce oxidative stress. One plant with a high antioxidant capacity is Spondias pinnata. This study attempts to demonstrate that Spondias pinnata leaf extract, at doses of 200, 400, and 600 mg/kg bw (body weight), can decrease oxidative stress in rats treated with isoniazid-rifampicin. Five treatment groups, normal control (K0), negative control (K1), treatment 1 (P1), treatment 2 (P2), and treatment 3 (P3) were included in this experiment. Male Wistar strain (8–12 weeks old) and weighed 200–220 g totalling 35 were used in this study. K1, P1, P2, and P3 rats were given isoniazid-rifampicin for 28 days. Rats in groups P1, P2, and P3 received Spondias pinnata leaf extract for 35 days (starting 7 days before induction). The ELISA method was used to assess oxidative damage through 8-hydroxy-2'-deoxyguanosin (8-OHdG) levels in rat liver tissue. In the rats' liver result, isoniazid and rifampicin cause DNA oxidative stress, as seen by an increase in 8-OHdG levels in K1 relative to K0. In comparison to K1, the administration of 200 mg/kg (P1), 400 mg/kg (P2), and 600 mg/kg (P3) of Spondias pinnata leaf extract lowered the amount of 8-OHdG in the liver of rats induced by isoniazid-rifampicin. This study shows that Spondias pinnata exhibited hepatoprotective effects, reducing 8-OHdG levels in isoniazid-rifampicin-induced rats.
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References
1. Fetensa G, Wirtu D, Etana B, Wakuma B, Tolossa T, Gugsa J, Gobena D, Fekadu G, Ragasa, MT, Ejeta E. Tuberculosis treatment delay and contributing factors within tuberculosis patients in Ethiopia: A systematic review and meta-analysis. Heliyon. 2024;10(7):1-23.
2. Zhang J, Takeuchi Y, Dong Y, Peng Z. Modelling the preventive treatment under media impact on tuberculosis: A comparison in four regions of China. Infect Dis Model. 2024;9(2):483–500.
3. Zhou C, Li T, Du J, Yin D, Li X, Li S. Toward tuberculosis elimination by understanding epidemiologic characteristics and risk factors in Hainan Province, China. Infect Dis Poverty. 2024;13(1):1–15.
4 Njiro BJ, Kisonga R, Joachim C, Sililo GA, Nkiligi E, Ibisomi L, Chirwa T, Francis JM. Epidemiology and treatment outcomes of recurrent tuberculosis in Tanzania from 2018 to 2021 using the National TB dataset. PLoS Negl Trop Dis 2024;18:1–19.
5. Holtgrewe LML, Johnson A, Nyhan K, Boffa J, Shenoi SV, Karat AS, Davis JL, Charalambous S. Burden of tuberculosis in underserved populations in South Africa: A systematic review and meta-analysis. PLOS Glob Public Heal. 2024;4(10):1–21.
6. Overton K, Varma R, Post JJ. Comparison of interferon-y release assays and the tuberculin skin test for diagnosis of tuberculosis in human immunodeficiency virus: A systematic review. Tuberc Respir Dis. 2018;81(1):59–72.
7. Rima DD, Legese D, Woldesemayat EM. Tuberculosis treatment delay and associated factors among pulmonary tuberculosis patients at public health facilities in Dale District and Yirgalem Town administration, Sidama Region, South Ethiopia. BMC Infect Dis. 2024;24(1):1–9.
8. Castle AC, HoeppnerI SS, Magodoro IM, Singh U, Moosa Y, Bassett IV. Wong EB, Siedner MJ, Team VS. Association between prior tuberculosis disease and dysglycemia within an HIV endemic, rural South African population. PLoS One. 2023;18(3):1–14.
9. Zinyakatira N, Ford N, Cox H. Association between HIV and acquisition of rifamycin resistance with first-line TB treatment: a systematic review and meta-analysis. BMC Infect Dis. 2024;24(1):1–13.
10. Pramana TY, Wasita B, Widyaningsih V, Cilmiaty R, Suroto, Mudigdo A, Purwanto B. The ethanol extract of Garcinia mangostana L peel reduces the isoniazid-induced liver damage in rats. Bali Med J. 2021;10:156–159.
11. Sahu S, Paul N, Ganeshpurkar A, Dubey N, Ganeshpurkar A. Catechin ameliorates hepatocellular damage caused by coadministration of isoniazid and rifampicin. Adv Redox Res. 2024;12:1-9.
12. Djabir YY, Arsyad A, Murdifin M, Tayeb R, Amir MN, Kamaruddin FAF, Najib NH. Kleinhovia hospita extract alleviates experimental hepatic and renal toxicities induced by a combination of antituberculosis drugs. J HerbMed Pharmacol. 2020;10:102–108.
13. Kargar JH, Pourahmad M, Abedi HA, Karimi M, Kargar JZ. Protective effects of salep against isoniazid liver toxicity in Wistar rats. J Tradit Complement Med. 2018;8(1):239–243.
14. Khan S, Mandal RK, Elasbali AM, Dar SA, Jawed A, Wahid M, Mahto H, Lohani M, Mishra BN, Akhter N, Rabaan AA, Haque S. Pharmacogenetic association between NAT2 gene polymorphisms and isoniazid induced hepatotoxicity: Trial sequence meta-analysis as evidence. Biosci Rep.
2019;39:1-15.
15. Mujahid M, Hussain T, Siddiqui HH, Hussain A. Evaluation of hepatoprotective potential of Erythrina indica leaves against antitubercular drugs induced hepatotoxicity in experimental rats. J Ayurveda Integr Med. 2017;8(1):7–12.
16. Rahman PH, Dwiwina RG, Pratiwi YS, Bashari MH. Curcuma longa L. prevents hepatotoxicity induced isoniazid and rifampicin: An experiment in Wistar rats model. Althea Med J. 2024;11(2):106–112.
17. Buabeid MA, Arafa ESA, Rani T, Ahmad FUD, Ahmed H, Hassan W, Murtaza G. Effects of Solanum lycopersicum L. (tomato) against isoniazid and rifampicin induced hepatotoxicity in Wistar albino rats. Brazilian J Biol. 2024;24:1-8.
18. Fayed AHM, Salama AAA, Ismaiel IE, Attia TA, Elbatran SA, Hassan A. Protective effects of Solanium nigrum methanolic extract against isoniazid/rifampicin induced hepatotoxicity in rats. J Appl Vet Sci. 2019;4(2):52–61.
19. Wali AF, Pillai JR, Al Dhaheri Y, Rehman MU, Shoaib A, Sarheed O, Jabnoun S, Razmpoor M, Rasool S, Paray BA, Ahmad P. Crocus sativus L. Extract containing polyphenols modulates oxidative stress and inflammatory response against anti-tuberculosis drugs-induced liver injury. Plants. 2020;9:1–14.
20. 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(39):1–11.
21. Dabadi P, AL-Suede FSR, Vm C, Shalavadi M, Gnanasekaran A. Hepatoprotective effect of hydro-alcohol extract of Mimusops elengi root against antitubercular drug-induced hepatotoxicity in rats. J Angiother. 2022;6(2):646–653.
22. Liu X, Zhao M, Mi J, Chen H, Sheng L, Li Y. Protective effect of bicyclol on anti-tuberculosis drug-induced liver injury in rats. Molecules. 2017;22(524):1–16.
23. Sahu N, Mishra G, Chandra HK, Nirala SK, Bhadauria M. Naringenin mitigates antituberculosis drugs induced hepatic and renal injury in rats. J Tradit Complement Med. 2020;10(1):26–35.
24. Ishtiaq S, Afridi MSK, Masood N. Amelioration of isoniazid and rifampicin-induced liver toxicity by Amaranthus graecizans subsp. Silvestris in rat. Bangladesh J Pharmacol. 2017;12(3):354–358.
25. Kosasih E, Chiuman L, Lister INE, Fachrial E. Hepatoprotective effect of citrus Sinensis peel extract against isoniazid and rifampicin-induced liver injury in Wistar rats. Maj Obat Tradis. 2019;24(3):197–203.
26. Mosa OF. Embelin mitigates hepatotoxicity induced by isoniazid and rifampicin in rats. Ukr Biochem J. 2024;96(3):48–56.
27. John P, Bhatia N, Kale P, Doshi G. Benefit of betaine in isoniazid-rifampicin-induced hepatotoxicity in rats. Iran J Toxicol. 2023;17(4):61–69.
28. Verma P, Srivastava S, Rao C V. Evaluation of “Leucas lanata” and assessment of its hepatoprotective effects on antitubercular drug-induced hepatic damage. Asian J Pharm Clin Res. 2018;11(6):451–456.
29. Iwo MI, Sjahlim SL, Rahmawati SF. Effect of Vernonia amygdalina del. Leaf ethanolic extract on intoxicated male Wistar rats liver. Sci Pharm. 2017;85(16):1-7.
30. Marianne M, Harahap U, Hasibuan PAZ, Thampati CM, Harefa HS. Hepatoprotective activity of the ethanol extract of Curcuma heyneana rhizome on isoniazid and rifampin-induced liver injury rats. J Herb Med Pharmacol. 2020;9(4):333–338.
31. Li G, Yang Y, Yang J, Suo Y, Xu H, Liu P, Wang J, Deng G, Feng T. Hepatoprotective effects of Malus hupehensis tea against isoniazid- and rifampicin-induced liver injury by regulating cytochrome P450 in mice. J Funct Foods. 2021;84:1-7.
32. Claudio SR, Gollucke APB, Yamamura H, Morais DR, Bataglion GA, Eberlin MN, Peres RC, Oshima CTF, Ribeiro DA. Purple carrot extract protects against cadmium intoxication in multiple organs of rats: Genotoxicity, oxidative stress, and tissue morphology analyses. J Trace Elem Med Biol. 2016;33:37–47.
33. Shabbir M, Afsar T, Razak S, Almajwal A, Khan MR. Phytochemical analysis and evaluation of hepatoprotective effect of Maytenus royleanus leaves extract against anti-tuberculosis drug-induced liver injury in mice. Lipids Health Dis. 2020;19(1):1–15.
34. Promprom W, Chatan W, Khambaione S, Somnate K, Munglue P. Effects of dietary supplementation of spray dried hog plum (Spondias pinnata Kurz) fruit powder on growth, digestive enzyme activity, and skin mucus immune parameters of climbing perch (Anabas testudineus (Bloch, 1972). Vet Integr Sci. 2024;22(1):315–334.
35. Laksemi DAAS. Biological activity of Spondias pinnata: A review. Indones J Biomed Sci. 2019;13(2):88–93.
36. Hazra B, Sarkar R, Mandal N. Spondias pinnata stem bark extract lessens iron-overloaded liver toxicity due to hemosiderosis in Swiss albino mice. Ann Hepatol. 2013;12(1):123–129.
37. Chaudhuri D, Ghate NB, Panja S, Mandal N. Role of phenolics from Spondias pinnata bark in amelioration of iron overload-induced hepatic damage in Swiss albino mice. BMC Pharmacol Toxicol. 2016;17(34):1–14.
38. Dóka O, Ficzek G, Simon G, Zsófi Z, Villangó S, Végvári G. Quantification of total polyphenol content in wine lees by conventional optical and photoacoustic spectroscopy. Oeno One. 2023;57(2):257–264.
39. Pai A, Rajendra MJ, Rao JS, Sudhakar M. Evaluation of anti-microbial, anti-oxidant activity and estimation of total flavonoid content in Sapindus trifoliatus seed extracts. Int J Pharm Pharm Sci. 2014;6(1):550–554.
40. Noipa T, Srijaranai S, Tuntulani T, Ngeontae W. New approach for evaluation of the antioxidant capacity based on scavenging DPPH free radical in micelle systems. Food Res Int. 2011;44(3):798–806.
41. Carmona JY, García-Moreno MV, Igartuburu JM, Garcia BC. Simplification of the DPPH assay for estimating the antioxidant activity of wine and wine by-products. Food Chem. 2014;165:198–204.
42. Li X, Zhang H, Xu L, Jin Y, Luo J, Li C, Zhao K, Zheng Y, Yu D, Zhao Y. miR-15a-3p Protects against isoniazid-induced liver injury via suppressing n-acetyltransferase 2 expression. Front Mol Biosci. 2021;8:1-12.
43. Kim J-H, Nam WS, Kim SJ, Kwon OK, Seung EJ, Jo JJ, Shresha R, Lee TH, Jeon TW, Ki SH, Lee HS, Lee S. Mechanism investigation of rifampicin-induced liver injury using comparative toxicoproteomics in mice. Int J Mol Sci. 2017;18(7):1-13.
44. Asare GA, Bronz M, Naidoo V, Kew MC. Interactions between aflatoxin B1 and dietary iron overload in hepatic mutagenesis. Toxicol. 2007;234(3):157–166.
45. Gomes de Moura CF, Pidone RFA, Lucke G, Boiago GAP, Fujiyama OCT, Ribeiro DA. Apple juice attenuates genotoxicity and oxidative stress induced by cadmium exposure in multiple organs of rats. J Trace Elem Med Biol. 2015;32:7–12.
46. Yew WW, Chang KC, Chan DP. Oxidative Stress and First-Line Antituberculosis Drug-Induced Hepatotoxicity. Antimicrob Agents Chemother. 2018;62(8):1-10.
47. Zentner I, Back H-M, Kagan L, Subbian S, Nagajyothi J, Srivastava S, Pasipanodya J, Gumbo T, Bisson GP, Vinnard C. Redox imbalance and oxidative DNA damage during isoniazid treatment of HIV-associated tuberculosis: a clinical and translational pharmacokinetic study. Front Pharmacol. 2020;11(1103):1-13.
48. Ayoub IM, El-Baset MA, Elghonemy MM, Bashandy SAE, Ibrahim FAA, Ahmed-Farid OAH, El Gendy AENG, Afifi SM, Esatbeyoglu T, Farrag ARH, Farag MA, Elshamy AI. Chemical profile of Cyperus laevigatus and its protective effects against thioacetamide-induced hepatorenal toxicity in rats. Molecules. 2022;27:1–23.
49. Laksemi DAAS, Arijana IGK, Sudarmaja IM, Ariwati NL, Tunas K, Damayanti PAA, Diarthini NLPE, Swastika IK, Wiryantini IAD. Ethanol extract of Spondias pinnata leaves reduces parasite number and increases macrophage phagocytosis capacity of mice infected by Plasmodium berghei. Indones Biomed J. 2021;13:40–47.
50. Wang X, Zhao J, Zhang R, Liu X, Ma C, Cao G, Wei Y, Yang P. Protective effect of Hedyotis diffusa Willd. Ethanol extract on isoniazid-induced liver injury in the zebrafish model. Drug Des Devel Ther. 2022;16:1995–2015.
51. Kuttiappan A, Chenchula S, Vanangamudi M, Bhatt S, Chikatipalli R, Shaila Bhanu P, Bandaru N. Hepatoprotective effect of flavonoid-rich fraction of Sesbania grandiflora: Results of In vivo, in vitro, and molecular docking studies. J Ayurveda Integr Med. 2024;15:1-13.
52. Chaudhuri D, Ghate NB, Panja S, Basu T, Shendge AK, Mandal N. Glycoside rich fraction from Spondias pinnata bark ameliorate iron overload-induced oxidative stress and hepatic damage in Swiss albino mice. BMC Complement Altern Med. 2016;16(1):1–12.
53. Dwita LP, Hikmawanti NPE, Husniah J, Hazraj M, Bela SN, Aryanti E. Plectranthus scutellarioides leaf extract protective effects against isoniazid and rifampicin-induced hepatotoxicity in Wistar rats. Trop J Nat Prod Res. 2022;6:1936–1940.
54. Ifidon OS, Oriakhi K. Effect of ethanol extract of Phyllantus niruri leaf on carbon tetrachloride-induced hepatotoxicity and oxidative stress in rats. Trop J Nat Prod Res. 2018;2:349–353.
55 Abubakar I, Kankara SS, Lawal U. Hepatoprotective effect of ethanol leaf extract of Ficus thonningii (Blume) against carbon tetrachloride (CCl4)-induced hepatotoxicity in Wistar rats. Trop J Nat Prod Res. 2022;6:406–410.