Research Article | Volume: 5, Issue: 1, Jan-Feb, 2017

DNP induced oxidative stress on blood components ameliorated by Pyrrole derivative of Tinospora cordifolia

K. C. Rashmi H. S. Aparna   

Open Access   

Published:  Jan 20, 2017

DOI: 10.7324/JABB.2017.50110

The intoxications and deaths caused by 2, 4-dinitrophenol (DNP) exposure through drugs, food supplements have been frequently reported and no specific treatment has been implemented to the toxic effects of DNP in adults and children. In this study, the purified compound (TCCP), a bioactive molecule from Tinospora cordifolia exhibited radical scavenging activities. Hence, we investigated the in vitro effect of TCCP on oxidative stress induced by DNP. Blood samples from healthy donors were treated with DNP (100µM/ml) for 2h. The DNP induced oxidative damage and effect of TCCP pre-treatment were determined by assessing the serum levels of cytoplasmic, lysosomal and oxidative stress markers. TCCP effectively inhibited DNP-induced oxidative stress on blood components, which was evidenced by the levels of endogenously generated reactive oxygen species and hydrogen peroxide. In addition, the depletion of GSH (reduced glutathione) content in DNP-treated cells was prevented by TCCP. Also, experimental results reflected the decreased expression of inflammation marker such as lipid peroxidase, catalase, LDH (lactate dehydrogenase), and phosphatase levels in cells with TCCP pre incubated DNP treated group. Therefore, these studies suggest the use of TCCP as an antioxidant and anti-inflammatory agent.

Keyword:     Tinospora cordifolia Pyrrole DNP oxidative stress.


Rashmi KC, Aparna HS. DNP induced oxidative stress on blood components ameliorated by Pyrrole derivative of Tinospora cordifolia. J App Biol Biotech. 2017; 5 (01): 059-065. DOI: 10.7324/JABB.2017.50110

Copyright: Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike license.

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1. Yen M, Ewald MB. Toxicity of weight loss agents. Journal of medical toxicology. 2012;8:145-152.

2. Lee HCH, Law CY, Chen ML, Lam YH, Chan AYW, Mak TWL. 2, 4-Dinitrophenol: A threat to Chinese body-conscious groups. Journal of the Chinese Medical Association. 2014;77:443-445.

3. Colman E. Dinitrophenol and obesity: an early twentieth-century regulatory dilemma. Regulatory Toxicology and Pharmacology. 2007;48:115-117.

4. Petróczi A, Ocampo JAV, Shah I, Jenkinson C, New R, James RA, et al. Russian roulette with unlicensed fat-burner drug 2, 4-dinitrophenol (DNP): evidence from a multidisciplinary study of the internet, bodybuilding supplements and DNP users. Substance abuse treatment, prevention, and policy. 2015 Oct 14;10:39. doi: 10.1186/s13011-015-0034-1.

5. Tewari A, Ali A, O'Donnell A, Butt M. Weight loss and 2, 4-dinitrophenol poisoning. British Journal of Anaesthesia. 2009; 102: 566-567.

6. Grundlingh J, Dargan PI, El-Zanfaly M, Wood DM. 2, 4-dinitrophenol (DNP): a weight loss agent with significant acute toxicity and risk of death. Journal of medical toxicology. 2011;7:205-212.

7. Jiukun J, Zhihua Y, Weidong H, Jiezan W. 2, 4-dinitrophenol poisoning caused by non-oral exposure. Toxicology and industrial health. 2010:0748233710387004.

8. Macnab AJ, Fielden SJ. Successful treatment of dinitrophenol poisoning in a child. Pediatric emergency care. 1998;14:136-138.

9. Bartlett J, Brunner M, Gough K. Deliberate poisoning with dinitrophenol (DNP): an unlicensed weight loss pill. Emergency medicine journal. 2010;27:159-160.

10. Takahashi M, Sunaga M, Hirata‐Koizumi M, Hirose A, Kamata E, Ema M. Reproductive and developmental toxicity screening study of 2, 4‐dinitrophenol in rats. Environmental toxicology. 2009;24:74-81.

11. Hsiao AL, Santucci KA, Seo-Mayer P, Mariappan MR, Hodsdon ME, Banasiak KJ, et al. Pediatric fatality following ingestion of dinitrophenol: postmortem identification of a “dietary supplement”. Clinical Toxicology. 2005;43:281-285.

12. Ash-Bernal R, Wise R, Wright SM. Acquired methemoglobinemia. Medicine. 2004;83:265-273.

13. Saha S, Ghosh S. Tinospora cordifolia: One plant, many roles. Ancient science of life. 2012;31:151-159.

14. Choudhary N, Siddiqui M, Azmat S, Khatoon S. Tinospora cordifolia: ethnobotany, phytopharmacology and phytochemistry aspects. International Journal of Pharmaceutical Sciences and Research. 2013;4:891-899.

15. Upadhyay AK, Kumar K, Kumar A, Mishra HS. Tinospora cordifolia (Willd.) Hook. f. and Thoms.(Guduchi)-validation of the Ayurvedic pharmacology through experimental and clinical studies. International journal of Ayurveda research. 2010;1:112-121.

16. Vaghamshi R, Jaiswal M, Patgiri B, Prajapati P, Ravishankar B, Shukla V. A comparative pharmacological evaluation of Taila (oil) and Ghrita (ghee) prepared with Guduchi (Tinospora cordifolia). Ayu. 2010;31:504-508.

17. Stanely Mainzen Prince P, Menon VP. Antioxidant action of Tinospora cordifolia root extract in alloxan diabetic rats. Phytotherapy Research. 2001;15:213-218.

18. Patgiri B, Umretia BL, Vaishnav PU, Prajapati PK, Shukla VJ, Ravishankar B. Anti-inflammatory activity of Guduchi Ghana (aqueous extract of Tinospora Cordifolia Miers.). Ayu. 2014;35:108-110.

19. Sharma A, Singh R. Screening of anti-inflammatory activity of certain indigenous drugs on carrageenin induced hind paw oedema in rats. Bulletin of Medico-Ethno-Botanical Research. 1981; 1:262-271.

20. Wesley J, Christina A, Chidambaranathan N, Livingston R, Ravikumar K. Effect of alcoho; ic extract of Tinospora cordifolia on acute and subacute inflammation. Pharmacologyonline. 2008; 3:683-687.

21. Pendse V, Dadhich A, Mathur P, Bal M, Madan B. Antiinflammatory, immunosuppressive and some related pharmacological actions of the water extract of Neem Giloe (Tinospora cordifolia): A preliminary report. Indian journal of pharmacology. 1977; 9: 221-224.

22. Utpalendu J, Chattopadhyay RN, Badri PS. Preliminary studies on anti-inflammatory activity of Zingiber officinale Rosc., Vitex negundo Linn and Tinospora cordifolia (willid) Miers in albino rats. Indian journal of pharmacology. 1999;31:232-233.

23. Tiwari M, Dwivedi U, Kakkar P. Tinospora cordifolia extract modulates COX-2, iNOS, ICAM-1, pro-inflammatory cytokines and redox status in murine model of asthma. Journal of ethnopharmacology. 2014;153:326-337.

24. Pushp P, Sharma N, Joseph G, Singh R. Antioxidant activity and detection of (−) epicatechin in the methanolic extract of stem of Tinospora cordifolia. Journal of food science and technology. 2013;50:567-572.

25. Pulido R, Bravo L, Saura-Calixto F. Antioxidant activity of dietary polyphenols as determined by a modified ferric reducing/antioxidant power assay. Journal of agricultural and food chemistry. 2000;48:3396-3402.

26. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free radical biology and medicine. 1999;26:1231-1237.

27. Santhosh MS, Sundaram MS, Sunitha K, Kemparaju K, Girish K. Viper venom-induced oxidative stress and activation of inflammatory cytokines: a therapeutic approach for overlooked issues of snakebite management. Inflammation Research. 2013;62:721-731.

28. Driver AS, Kodavanti PRS, Mundy WR. Age-related changes in reactive oxygen species production in rat brain homogenates. Neurotoxicology and teratology. 2000;22:175-181.

29. Barja G. Minireview: the quantitative measurement of H2O2 generation in isolated mitochondria. Journal of bioenergetics and biomembranes. 2002;34:227-233.

30. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical biochemistry. 1979;95:351-358.

31. Chandrashekar K. d-Aspartic acid induced oxidative stress and mitochondrial dysfunctions in testis of prepubertal rats. Amino acids. 2010;38:817-827.

32. Aebi H. Catalase in vitro. Methods in enzymology. 1984;105:121-126.

33. Tenniswood M, Bird C, Clark A. Acid phosphatases: androgen dependent markers of rat prostate. Canadian journal of biochemistry. 1976;54:350-357.

34. Walter K, Schutt C. Alkaline phosphatase in serum. Methods of enzymatic analysis. 1974;2:860-864.

35. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J biol Chem. 1951;193:265-275.

36. Nur E, Biemond BJ, Otten HM, Brandjes DP, Schnog JJB. Oxidative stress in sickle cell disease; pathophysiology and potential implications for disease management. American journal of hematology. 2011;86:484-489.

37. Iuchi Y. Anemia caused by oxidative stress: INTECH Open Access Publisher; 2012.

38. Rana S. Free radical scavenging and metal chelation by Tinospora cordifolia, a possible role in radioprotection. Indian journal of experimental biology. 2002;40:727-734.

39. Daghman N, Elder G, Savage G, Winter P, Lappin T, Maxwell A. Erythropoietin production: evidence for multiple oxygen sensing pathways. Annals of hematology. 1999;78:275-278.

40. Zierle J, Bissinger R, Egler J, Lang F. Lapatinib Induced Suicidal Death of Human Erythrocytes. Cellular Physiology and Biochemistry. 2015;37:2275-2287.

41. Blokhina O, Virolainen E, Fagerstedt KV. Antioxidants, oxidative damage and oxygen deprivation stress: a review. Annals of botany. 2003;91:179-194.

42. Kelso GF, Porteous CM, Coulter CV, Hughes G, Porteous WK, Ledgerwood EC, et al. Selective targeting of a redox-active ubiquinone to mitochondria within cells antioxidant and antiapoptotic properties. Journal of Biological Chemistry. 2001;276:4588-4596.

43. Han YW, Kim SZ, Kim SH, Park WH. The changes of intracellular H 2 O 2 are an important factor maintaining mitochondria membrane potential of antimycin A-treated As4. 1 juxtaglomerular cells. Biochemical pharmacology. 2007;73:863-872.

44. Park WH, Han YW, Kim SH, Kim SZ. An ROS generator, antimycin A, inhibits the growth of HeLa cells via apoptosis. Journal of cellular biochemistry. 2007;102:98-109.

45. Stanely P, Prince M, Menon VP. Hypoglycaemic and other related actions of Tinospora cordifolia roots in alloxan-induced diabetic rats. Journal of ethnopharmacology. 2000;70:9-15.

46. Prince P, Kamalakkannan N, Menon VP. Restoration of antioxidants by ethanolic Tinospora cordifolia in alloxan-induced diabetic Wistar rats. Acta Pol Pharm. 2004;61:283-287.

47. Umamaheswari S, Prince PSM. Antihyperglycaemic effect of 'ilogen-excel', an ayurvedic herbal formulation in streptozotocin-induced diabetes mellitus. Acta Poloniae Pharmaceutica. 2007;64: 53-61.

48. Sharma V, Pandey D. Protective role of Tinospora cordifolia against lead-induced hepatotoxicity. Toxicology international. 2010;17:12-17.

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