Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter October 4, 2016

The ameliorating effect of Centella asiatica ethanolic extract on albino rats treated with isoniazid

  • Kavisa Ghosh EMAIL logo , N. Indra and G. Jagadeesan

Abstract

Background:

Isoniazid, also called isonicotinyl hydrazine (INH), is a commonly used drug for treating tuberculosis. The main drawback is its toxic side effects. Centella asiatica has long been used in the Ayurvedic system of medicine owing to its wide medicinal properties. This study was designed to examine the effectiveness of C. asiatica ethanolic leaf extract (CA) on INH-treated albino rats.

Methods:

The adverse effects induced by INH (50 mg/kg bw) administration on haematological parameters, oxidative status (thiobarbituric acid-reactive substances, superoxide dismutase, catalase, and reduced glutathione), liver and kidney function markers, and their amelioration by various concentrations of CA (20, 40, 60, and 100 mg/kg bw) or silymarin (SIL) (50 mg/kg bw, administered before 1 h of INH treatment for 30 days to rats) were studied. Moreover, histological studies were carried out in liver and kidney tissues of rats treated with the most effective concentration to further support the possible effectiveness of CA on INH-intoxicated rats.

Results:

All the affected parameters returned to near-normal levels, and the effective concentration of extract was found to be 100 mg/kg bw. The histology of both the liver and the kidneys subsequently supported the effectiveness of CA (100 mg/kg bw).

Conclusions:

Altogether, the results suggest that CA at 100 mg/kg bw can substantially reduce the toxic effects of INH.

Acknowledgments

The authors gratefully acknowledge financial support from the University Grants Commission (UGC), New Delhi, India [principal investigator: Dr. N. Indra, co-investigator: Dr. G. Jagadeesan; F. No. 42-595/2013(SR), dated 22.03.2013] and Annamalai University for infrastructural support for carrying out the research work.

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

  2. Research funding:UGC, New Delhi, India [F. No. 42-595/2013(SR), dated 22.03.2013].

  3. Employment or leadership:None declared.

  4. Honorarium:None declared.

  5. Competing interests:The funding organisation played no role in the study design or in the collection, analysis, and interpretation of the data; or in the writing of the report; or in the decision to submit the report for publication.

References

1. World Health Organization. Global tuberculosis report 2013. WHO, 2013.Search in Google Scholar

2. Adebayo AJ, Adetokunbo OA, Kehinde AJ, Olamide AE, Oluwatosin A. Microsomal lipid peroxidation, antioxidant enzyme activities in brain of male rats during long-term exposure to isoniazid. J Drug Metab Toxicol 2012;3:127.10.4172/2157-7609.1000127Search in Google Scholar

3. Zumla A, Nahid P, Cole ST. Advances in the development of new tuberculosis drugs and treatment regimens. Nat Rev Drug Discov 2013;12:388–404.10.1038/nrd4001Search in Google Scholar PubMed

4. Centers for Disease Control and Prevention, Division of Tuberculosis Elimination (DTBE). Tuberculosis: treatment. Online: http://www.cdc.gov/tb/topic/treatment/default.htm. Accessed: 8 Sep 2014.Search in Google Scholar

5. Mahapatra S, Woolhiser LK, Lenaerts AJ, Johnson JL, Eisenach KD, Joloba ML, et al. A novel metabolite of antituberculosis therapy demonstrates host activation of isoniazid and formation of the isoniazid-NAD+ adduct. Antimicrob Agents Chemother 2012;56:28–35.10.1128/AAC.05486-11Search in Google Scholar PubMed PubMed Central

6. Mattioni S, Zamy M, Mechai F, Raynaud JJ, Chabrol A, Aflalo V, et al. Isoniazid-induced recurrent pancreatitis. JOP J Pancreas 2012;13:314–6.Search in Google Scholar

7. Blair IA, Mansilla Tinoco R, Brodie MJ, Clare RA, Dollery CT, Timbrell JA, et al. Plasma hydrazine concentrations in man after isoniazid and hydralazine administration. Hum Toxicol 1985;4:195–202.10.1177/096032718500400210Search in Google Scholar PubMed

8. MMWR. Centers for Disease Control and Prevention. Severe isoniazid-associated liver injuries among persons being treated for latent tuberculosis infection – United States, 2004–2008. Morb Mortal Wkly Rep 2010;59:224–9.Search in Google Scholar

9. Luntz GR, Smith SG. Effect of isoniazid on carbohydrate metabolism in controls and diabetics. Br Med J 1953;1: 296–9.10.1136/bmj.1.4805.296Search in Google Scholar PubMed PubMed Central

10. Mukherjee S, Dugad S, Bhandare R, Pawar N, Jagtap S, Pawar PK, et al. Evaluation of comparative free-radical quenching potential of Brahmi (Bacopa monnieri) and Mandookparni (Centella asiatica). Ayu 2011;32:258–64.10.4103/0974-8520.92549Search in Google Scholar PubMed PubMed Central

11. Gohil KJ, Patel JA, and Gajjar AK. Pharmacological review on Centella asiatica: a potential herbal cure-all. Indian J Pharm Sci 2010;72:546–56.10.4103/0250-474X.78519Search in Google Scholar PubMed PubMed Central

12. Meena H, Pandey HK, Pandey P, Arya MC, Ahmed Z. Evaluation of antioxidant activity of two important memory enhancing medicinal plants Baccopa monnieri and Centella asiatica. Indian J Pharmacol 2012;44:114–7.10.4103/0253-7613.91880Search in Google Scholar PubMed PubMed Central

13. Yu QL, Duan HQ, Takaishi Y, Gao WY. A novel triterpene from Centella asiatica. Molecules 2006;11:661–5.10.3390/11090661Search in Google Scholar PubMed PubMed Central

14. Seevaratnam V, Banumathi P, Premalatha MR, Sundaram SP, Arumugam T. Functional properties of Centella asiatica (L.): a review. Int J Pharm Pharm Sci 2012;4:8–14.Search in Google Scholar

15. Ghosh K, Indra N. Phytochemistry, in vitro free radical scavenging, chelating and toxicity of Centela asiatica L. (Apiaceae) ethanolic leaf extract. Int J Pharm Sci Rev Res 2014;29:328–34.Search in Google Scholar

16. Santhosh S, Sini TK, Anandan R, Mathew PT. Hepatoprotective activity of chitosan against isoniazid and rifampicin-induced toxicity in experimental rats. Eur J Pharmacol 2007;572:69–73.10.1016/j.ejphar.2007.05.059Search in Google Scholar PubMed

17. Rana SV, Pal R, Vaiphei K, Ola RP, Singh K. Hepatoprotection by carotenoids in isoniazid-rifampicin induced hepatic injury in rats. Biochem Cell Biol NBC Res 2010;88:819–34.10.1139/O10-023Search in Google Scholar

18. Sasaki T, Matsy S, Sonae A. Effect of acetic acid concentration on the color reaction in the O-toluidine boric acid method for blood glucose estimation. Rinsho Kagak 1972;1:346–53.Search in Google Scholar

19. Dacie JV, Lewis SN. Practical haematology, 6th ed. Edinburg: Churchill Livingstone, 1984.Search in Google Scholar

20. Hogberg J, Larson RE, Kristoferson A, Orrenius S. NADPH-dependent reductase solubilised from microsomes of peroxidation and its activity. Biochem Biophys Res Commun 1974;56:836–42.10.1016/0006-291X(74)90681-0Search in Google Scholar

21. Kakkar R, Mantha SV, Prasad RK, Kalra J. Increased oxidative stress in rat liver and pancrease during progression of streptozotocin induced diabetes. Clin Sci 1998;94:69–74.10.1042/cs0940623Search in Google Scholar

22. Sinha AK. Colorimetric assay of catalase. Anal Biochem 1972;47:389–94.10.1016/0003-2697(72)90132-7Search in Google Scholar

23. Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione-s-transferase activities in rat lung and liver. Biochem Biophys Acta 1979;582:67–78.10.1016/0304-4165(79)90289-7Search in Google Scholar

24. Lowry OH, Rosebrough NJ, Farn AL, Randall RJ. Protein measurement with the folic phenol reagent. J Biol Chem 1951;193:265–75.10.1016/S0021-9258(19)52451-6Search in Google Scholar

25. Doumas BT, Watson WA, Biggs HC. Albumin standards and management of serum albumin with bromocresol green. Clin Chim Acta 1971;31:87–96.10.1016/0009-8981(71)90365-2Search in Google Scholar

26. Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957;28:56–63.10.1093/ajcp/28.1.56Search in Google Scholar

27. King EJ, Armstrong AR. A convenient method for determining of serum and bile phosphatase activity. J Can Med Assoc 1934;31:376–81.Search in Google Scholar

28. Malloy E, Evelyn K. The determination of bilirubin with the photoelectric colorimeter. J Biol Chem 1937;119:481–5.10.1016/S0021-9258(18)74392-5Search in Google Scholar

29. Patton CJ, Crouch SR. Spectrophotometric and kinetics investigation of the Berthelot reaction for the determination of ammonia. Anal Chem 1977;49:464–9.10.1021/ac50011a034Search in Google Scholar

30. Antony B, Santhakumari G, Merina B, Sheeba V, Mukkadan J. Hepatoprotective effect of Centella asiatica (L) in carbon tetrachloride-induced liver injury in rats. Indian J Pharmaceut Sci 2006;68:772–6.10.4103/0250-474X.31013Search in Google Scholar

31. Abdulla MA, Al-Bayaty FH, Younis LT, Abu Hassan MI. Anti-ulcer activity of Centella asiatica leaf extract against ethanol-induced gastric mucosal injury in rats. J Med Plants Res 2010;4:1253–9.Search in Google Scholar

32. Pradhan SC, Girish C. Hepatoprotective herbal drug, SIL from experimental pharmacology to clinical medicine. Indian J Med Res 2006;124:491–504.Search in Google Scholar

33. Wilmink T, Frick TW. Drug-induced pancreatitis. Drug Safety 1996;14:406–23.10.2165/00002018-199614060-00006Search in Google Scholar PubMed

34. Pandey AS, Surana A. Isoniazid-induced recurrent acute pancreatitis. Trop Doct 2011;41:249–50.10.1258/td.2011.110127Search in Google Scholar PubMed

35. Tousif S, Singh DK, Ahmad S, Moodley P, Bhattacharyya M, Van Kaer L, et al. Isoniazid induces apoptosis of activated CD4+ T cells: implications for post-therapy tuberculosis reactivation and reinfection. J Biol Chem 2014;289:30190–5.10.1074/jbc.C114.598946Search in Google Scholar PubMed PubMed Central

36. Comstock GW, Baum C, Snider DE Jr. Isoniazid prophylaxis among Alaskan Eskimos: a final report of the bethel isoniazid studies. Am Rev Respir Dis 1979;119:827–30.Search in Google Scholar

37. Yilmaz HR, Uz E, Gökalp O, Ozçelik N, Ciçek E, Ozer MK. Protective role of caffeic acid phenethyl ester and erdosteine on activities of purine-catabolizing enzymes and level of nitric oxide in red blood cells of isoniazid-administered rats. Toxicol Ind Health 2008;24:519–24.10.1177/0748233708098128Search in Google Scholar PubMed

38. Huang SC, Benz EJ. Chapter 8: posttranscriptional factors influencing the hemoglobin content of the red cell. In: Steinberg MH, Higgs D, Nagel RL, editors. Disorders of hemoglobin: genetics, pathophysiology, and clinical management. Cambridge, UK: Cambridge University Press, 2001:146–73.Search in Google Scholar

39. Hutchison RE, McPherson RA, Schexneider KI. Chapter 30: basic examination of blood and bone marrow. In: McPherson RA, Pincus MR, editors. Henry’s clinical diagnosis and management by laboratory methods, 22nd ed. Philadelphia, PA: Elsevier Saunders, 2011.Search in Google Scholar

40. Singh A, Bhat TK, Sharma OP. Clinical biochemistry of hepatotoxicity. J Clinic Toxicol 2011;S4:001. doi:10.4172/2161-0495.S4-001.Search in Google Scholar

41. Hussain SM, Frazier JM. Cellular toxicity of hydrazine in primary rat hepatocytes Toxicol Sci 2002;69:424–32.10.1093/toxsci/69.2.424Search in Google Scholar PubMed

42. 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;19:517–22.10.1191/096032700674230830Search in Google Scholar PubMed

43. Lei XG, Cheng WH, McClung JP. Metabolic regulation and function of glutathione peroxidase-1. Annu Rev Nutr 2007;27:41–61.10.1146/annurev.nutr.27.061406.093716Search in Google Scholar PubMed

44. Rao RR. Mechanism of drug induced hepatotoxicity. Ind J Pharmacol 1973;5:313–8.Search in Google Scholar

45. Jaydeokar AV, Bandawane DD, Bibave KH, Patil TV. Hepatoprotective potential of Cassia auriculata roots on ethanol and antitubercular drug-induced hepatotoxicity in experimental models. Pharm Biol. 2014;52(3):344–55.10.3109/13880209.2013.837075Search in Google Scholar PubMed

46. Thapa BR, Walia A. Liver function tests and their interpretation. Indian J Pediatr 2007;74:663–71.10.5005/jp/books/12548_22Search in Google Scholar

47. Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, and Menzies D. Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. Am J Respir Crit Care Med 2003;167: 1472–7.10.1164/rccm.200206-626OCSearch in Google Scholar PubMed

48. Sharmila R, Sindhu G, Arockianathan PM. Nephroprotective effect of β-sitosterol on N-diethylnitrosamine initiated and ferric nitrilotriacetate promoted acute nephrotoxicity in Wistar rats. J Basic Clin Physiol Pharmacol 2016;27:473–82.10.1515/jbcpp-2015-0085Search in Google Scholar PubMed

49. Jadhav R, Mateenuddin M. Effect of Nigella sativa oil on hepatotoxicity induced by antitubercular drugs in albino rats. Indian Med Gazette 2013;147:145–51.Search in Google Scholar

50. Sankar M, Rajkumar J, Sridhar D. Hepatoprotective activity of heptoplus on isoniazid and rifampicin induced liver damage in rats. Indian J Pharm Sci 2015;77:556–62.10.4103/0250-474X.169028Search in Google Scholar PubMed PubMed Central

51. Hussein OE, Germoush MO, Mahmoud AM. Ruta graveolens protects against isoniazid/rifampicin-induced nephrotoxicity through modulation of oxidative stress and inflammation. Glob J Biotechnol Biomater Sci 2016;1:008–13.Search in Google Scholar

Received: 2016-4-16
Accepted: 2016-7-16
Published Online: 2016-10-4
Published in Print: 2017-1-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 6.6.2023 from https://www.degruyter.com/document/doi/10.1515/jbcpp-2016-0059/html
Scroll to top button