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Scopoletin a potential phytochemical therapy for antitubercular treatment drug induced liver injury (ATT-DILI) model in Wistar rats

  • Swati Sharma , Vishal Sharma , Sunil Taneja , Alka bhatia , Aishwarya Anand , Amol N. Patil ORCID logo EMAIL logo and Dibyajyoti Banerjee
Published/Copyright: September 22, 2023

Abstract

Objectives

The hepatoprotective properties of scopoletin have been explored in carbon tetrachloride (CCl4) induced liver injury but not in drug-induced liver injury (DILI) scenarios. Only N-acetyl-cysteine (NAC) has proven efficacy in DILI treatment. Accordingly, we conducted a study to assess the hepatoprotective action of scopoletin in the anti-tubercular treatment (ATT)-DILI model in Wistar rats, if any.

Methods

A total of 36 rats were evaluated, with six in each group. A 36-day ATT at 100 mg/kg dose for isoniazid, 300 mg/kg for rifampicin and 700 mg/kg for pyrazinamide were fed to induce hepatotoxicity in rats. Group I and II–VI received normal saline and ATT, respectively. Oral scopoletin (1,5 and 10 mg/kg) and NAC 150 mg/kg were administered in groups III, IV, V and VI, respectively, once daily for the last 15 days of the experiment. LFT monitoring was performed at baseline, days 21, 28, and 36. Rats were sacrificed for the histopathology examination.

Results

Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin levels were significantly increased in group II (receiving ATT) compared to normal control on day 28 and day 36 (p<0.05). All three doses of scopoletin and NAC groups led to the resolution of AST, ALT, ALP, and bilirubin changes induced by ATT medications effect beginning by day 28 and persisting on day 36 (p<0.01). An insignificant effect was observed on albumin and total protein levels. The effect was confirmed with antioxidants and histopathology analysis.

Conclusions

The study confirms the hepatoprotective efficacy of scopoletin in a more robust commonly encountered liver injury etiology.


Corresponding author: Dr Amol N. Patil, Associate Professor, Department of Pharmacology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India, Phone: +91 9990245973, 7087008957 28, E-mail:

  1. Ethical approval: Study protocol was approved by the Animal Ethics Committee (761/IAEC/110-D) and all experiments complied with the ARRIVE (Animal Research: Reporting of In Vivo Experiments) 2.0 guidelines.

  2. Informed consent: Informed consent was not needed in this study.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Competing interests: Authors state no conflict of interest.

  5. Research funding: None declared.

  6. Data availability: Raw data can be availed from the corresponding author upon reasonable request.

References

1. Devarbhavi, H. An update on drug-induced liver injury. J Clin Exp Hepatol 2012;2:247–59. https://doi.org/10.1016/j.jceh.2012.05.002.Search in Google Scholar

2. Bessone, F, Hernandez, N, Tagle, M, Arrese, M, Parana, R, Méndez-Sánchez, N, et al.. Drug-induced liver injury: a management position paper from the Latin American Association for Study of the liver. Ann Hepatol 2021;24:100321. https://doi.org/10.1016/j.aohep.2021.100321.Search in Google Scholar

3. Sharma, S, Anand, A, Bhatia, A, Sharma, V, Singh, AK, Banerjee, D, et al.. Pharmacological evaluation of scopoletin in the carbon tetrachloride-induced hepatotoxicity model in Wistar rats. J Pharm BioAllied Sci 2022;14:201–6. https://doi.org/10.4103/jpbs.jpbs_333_22.Search in Google Scholar

4. Singh, AK, Verma, S, Kumar, MP, Soni, H, Sharma, S, Sharma, S, et al.. Appropriate chemopreventive strategy for anti-tubercular therapy related liver injury is unsettled: results from a systematic review and network meta-analysis. Expet Rev Clin Pharmacol 2020;13:1253–62. https://doi.org/10.1080/17512433.2020.1835468.Search in Google Scholar

5. Adhvaryu, MR, Reddy, NM, Vakharia, BC. Prevention of hepatotoxicity due to anti tuberculosis treatment: a novel integrative approach. World J Gastroenterol 2008;14:4753–62. https://doi.org/10.3748/wjg.14.4753.Search in Google Scholar

6. Garg, G, Patil, AN, Kumar, R, Bhatia, A, Kasudhan, KS, Pattanaik, S. Protective role of Convolvulus pluricaulis on lipid abnormalities in high-fat diet with low dose streptozotocin-induced experimental rat model. J Ayurveda Integr Med 2020;11:426–31. https://doi.org/10.1016/j.jaim.2020.06.011.Search in Google Scholar

7. Garg, G, Patil, A, Singh, J, Kaushik, N, Praksah, A, Pal, A, et al.. Pharmacological evaluation of Convolvulus pluricaulis as hypolipidaemic agent in Triton WR-1339-induced hyperlipidaemia in rats. J Pharm Pharmacol 2018;70:1572–80. https://doi.org/10.1111/jphp.13004.Search in Google Scholar

8. Subramanya, SB, Venkataraman, B, Meeran, MFN, Goyal, SN, Patil, CR, Ojha, S. Therapeutic potential of plants and plant derived phytochemicals against acetaminophen-induced liver injury. Int J Mol Sci 2018;19:3776. https://doi.org/10.3390/ijms19123776.Search in Google Scholar

9. Polavarapu, R, Spitz, DR, Sim, JE, Follansbee, MH, Oberley, LW, Rahemtulla, A, et al.. Increased lipid peroxidation and impaired antioxidant enzyme function is associated with pathological liver injury in experimental alcoholic liver disease in rats fed diets high in corn oil and fish oil. Hepatology 1998;27:1317–23. https://doi.org/10.1002/hep.510270518.Search in Google Scholar

10. Batra, GK, Anand, A, Sharma, S, Sharma, S, Bhansali, S, Patil, AN. Scopoletin improves glucose homeostasis in the high-fructose high-fat diet-induced diabetes model in Wistar rats. J Med Food 2023;26:270–4. https://doi.org/10.1089/jmf.2022.K.0153.Search in Google Scholar

11. Batra, GK, Mothsara, C, Sharma, S, Anand, A, Bhatia, A, Bhansali, S, et al.. Dose-response evaluation of scopoletin, a phytochemical, in a high-fructose high-fat diet-induced dyslipidemia model in Wistar rats. J Med Food 2023;26:319–27. https://doi.org/10.1089/jmf.2022.K.0120.Search in Google Scholar

12. Zhao, H, Wang, Y, Zhang, T, Wang, Q, Xie, W. Drug-induced liver injury from anti-tuberculosis treatment: a retrospective cohort study. Med Sci Mon 2020;26:e920350. https://doi.org/10.12659/MSM.920350.Search in Google Scholar

13. Attri, S, Rana, SV, Vaiphei, K, Sodhi, CP, Katyal, R, Goel, RC, et al.. Isoniazid- and rifampicin-induced oxidative hepatic injury--protection by N-acetylcysteine. Hum Exp Toxicol 2000;19:517–22. https://doi.org/10.1191/096032700674230830.Search in Google Scholar

14. Ruan, LY, Fan, JT, Hong, W, Zhao, H, Li, MH, Jiang, L, et al.. Isoniazid-induced hepatotoxicity and neurotoxicity in rats investigated by 1H NMR based metabolomics approach. Toxicol Lett 2018;295:256–69. https://doi.org/10.1016/j.toxlet.2018.05.032.Search in Google Scholar

15. Naik, SR, Panda, VS. Hepatoprotective effect of Ginkgoselect Phytosome in rifampicin induced liver injury in rats: evidence of antioxidant activity. Fitoterapia 2008;79:439–45. https://doi.org/10.1016/j.fitote.2008.02.013.Search in Google Scholar

16. Kovalenko, VM, Bagnyukova, TV, Sergienko, OV, Bondarenko, LB, Shayakhmetova, GM, Matvienko, AV, et al.. Epigenetic changes in the rat livers induced by pyrazinamide treatment. Toxicol Appl Pharmacol 2007;225:293–9. https://doi.org/10.1016/j.taap.2007.08.011.Search in Google Scholar

17. Zhao, H, Si, ZH, Li, MH, Jiang, L, Fu, YH, Xing, YX, et al.. Pyrazinamide-induced hepatotoxicity and gender differences in rats as revealed by a 1H NMR based metabolomics approach. Toxicol Res 2016;6:17–29. https://doi.org/10.1039/c6tx00245e.Search in Google Scholar

18. Breitbart, R, Abu-Kishk, I, Kozer, E, Ben-Assa, E, Goldstein, LH, Youngster, I, et al.. Intraperitoneal N-acetylcysteine for acute iron intoxication in rats. Drug Chem Toxicol 2011;34:429–32. https://doi.org/10.3109/01480545.2011.564176.Search in Google Scholar

19. Kalimeris, K, Briassoulis, P, Ntzouvani, A, Nomikos, T, Papaparaskeva, K, Politi, A, et al.. N-acetylcysteine ameliorates liver injury in a rat model of intestinal ischemia reperfusion. J Surg Res 2016;206:263–72. https://doi.org/10.1016/j.jss.2016.08.049.Search in Google Scholar

20. Walayat, S, Shoaib, H, Asghar, M, Kim, M, Dhillon, S. Role of N-acetylcysteine in non-acetaminophen-related acute liver failure: an updated meta-analysis and systematic review. Ann Gastroenterol 2021;34:235–40. https://doi.org/10.20524/aog.2021.0571.Search in Google Scholar

21. Eminzade, S, Uraz, F, Izzettin, FV. Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals. Nutr Metab 2008;5:18. https://doi.org/10.1186/1743-7075-5-18.Search in Google Scholar PubMed PubMed Central

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. https://doi.org/10.3390/molecules22040524.Search in Google Scholar PubMed PubMed Central

23. Sharma, V, Kaur, R, Sharma, VL. Ameliorative potential of Adhatoda vasica against anti-tubercular drugs induced hepatic impairments in female Wistar rats in relation to oxidative stress and xeno-metabolism. J Ethnopharmacol 2021;270:113771. https://doi.org/10.1016/j.jep.2020.113771.Search in Google Scholar PubMed

24. Rathod, R, Mohindra, R, Vijayakumar, A, Soni, RK, Kaur, R, Kumar, A, et al.. Essential oil nebulization in mild COVID-19(EONCO): early phase exploratory clinical trial. J Ayurveda Integr Med 2022;13:100626. https://doi.org/10.1016/j.jaim.2022.100626.Search in Google Scholar PubMed PubMed Central

Received: 2023-06-13
Accepted: 2023-08-28
Published Online: 2023-09-22

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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