Skip to main content
Intended for healthcare professionals
Free access
Research article
First published September 2006

Protective Effect of Andrographis paniculata and Andrographolide on Cyclophosphamide-Induced Urothelial Toxicity

K. Sheeja, MSc, and Girija Kuttan, PhDView all authors and affiliations
All Articles
https://doi.org/10.1177/1534735406291984

Abstract

The protective effect of Andrograhis paniculata and andrographolide (ANDLE) against cyclophosphamide (CTX)-induced urothelial toxicity was investigated in this study. Pretreatment of Swiss albino mice with A paniculata extract (10 mg/dose/animal intraperitoneally [ip]) and ANDLE (500 μg/dose/animal ip) could significantly reduce CTX (1.5 nmol/kg body weight)-induced urothelial toxicity. Morphological and histopathological analysis of urinary bladder of CTX-treated mice showed severe inflammation and dark coloration, whereas A paniculata and ANDLE-treated mice showed almost normal bladder morphology. Elevation of urinary protein level (7.33±0.3 g/L) by CTX administration was reduced by A paniculata (3.78 ± 0.4 g/L) and ANDLE treatment (4.19 ± 0.1 g/L). Urinary urea N2level, which was elevated after 48 hours of CTX administration (24.25 ± 0.2 g/L) was found to be reduced by the treatment with A paniculata (14.19 ± 0.5 g/L) and ANDLE (15.79 ± 0.4 g/L). A decreased level of reduced glutahione (GSH) content in liver (2.81 ± 0.1 nmol/mg protein) and bladder (1.20 ± 0.2 nmol/mg protein) after CTX administration was also increased by the treatment with A paniculata (liver: 5.78 ± 0.3 nmol/mg protein; bladder: 2.96 ± 0.2 nmol/mg protein) and ANDLE (liver: 5.14 ± 0.3 nmol/mg protein; bladder: 2.84 ± 0.2 nmol/mg protein). Production of the proinflammatory cytokine, tumor necrosis factor-α, which was elevated during CTX administration, was found to be inhibited by A paniculata and ANDLE treatment. The lowered level of interleukin-2 and interferon-γ during CTX treatment was elevated by the administration of A paniculata and ANDLE.

References

Morais MM, Belarmino-Filho JN, Brito GAC, Ribeiro RA. Pharmacological and histopathological study of cyclophosphamide-induced hemorrhagic cystitis—comparison of the effect of dexamethasone and Mesna. Braz J Med Biol Res. 1999;32:1211-1215.
Google Scholar
Fleming RE. An overview of cyclophosphamide and ifosfamide pharmacology. Pharmacotherapy. 1997;17:146s-154s.
Google Scholar
Mirkes PE. Cyclophosphamide teratogenesis: a review. Teratogen Carcinogen Mutagen. 1985;5:75-88.
Google Scholar
Foad BSI, Hess EV. Urinary bladder complication with therapy. Arch Intern Med. 1976;136:616-619.
Google Scholar
Boddy AV, Yule SM. Metabolism and pharmacokinetics of oxazaphosphorines. Clin Pharmacokinet. 2000;38:291-304.
Google Scholar
Cox PJ. Cyclophosphamide cystitis—identification of acrolein as the causative agent. Biochem Pharmacol. 1979;28:2045-2049.
Google Scholar
Berlin L, MuHugh SL, eds. Physician’s Drug Handbook. 8th ed. Spring House, Pa: Spring House; 1999.
Google Scholar
Trigg ME, O’Reilly J, Rumelhart S, Morgan D, Holida M, De Alarcon P. Prostaglandin E1 bladder instillations to control severe hemorrhagic cystitis. JUrol. 1990;143:92-94.
Google Scholar
Mohiuddin J, Prentice HG, Schey S, Blacklock H, Dandona P. Treatment of cyclophosphamide-induced cystitis with prostaglandin E2. Ann Intern Med. 1984;101:142-142.
Google Scholar
Shurafa M, Shumaker E, Cronin S. Prostaglandin F2-alpha bladder irrigation for control of intractable cyclophosphamide induced hemorrhagic cystitis. J Urol. 1987;137:1230-1231.
Google Scholar
Grinberg-Funes DJ, Sheldon C, Weiss M. The use of prostaglandin F2-alpha for the prophylaxis of cyclophosphamide-induced cystitis in rats. J Urol. 1990;28:1500-1504.
Google Scholar
Kumar KBH, Kuttan R. Chemoprotective activity of an extract of Phyllanthus amarus against cyclophosphamide-induced toxicity in mice. Phytomedicine. 2005;12:495-500.
Google Scholar
Bin-Hafeez B, Ahmad I, Haque R, Raisuddin S. Protective effect of Cassia occidentalis L. on cyclophosphamide-induced suppression of humoral immunity in mice. J Ethnopharmacol. 2001;75:13-18.
Google Scholar
Haque R, Bin-Hafeez B, Ahmad I, Parvez S, Pandey S, Raisuddin S. Protective effect of Emblica officinalis Gaertn. in cyclophosphamide-treated mice. Human Exp Toxicol. 2001;20:643-650.
Google Scholar
Sharma N, Trikha P, Athar M, Raisuddin S. Inhibitory effect of Emblica officinalis on the in vivo clastogenicity of benzo[a]pyrene and cyclophosphamide in mice. Human Exp Toxicol. 2000; 19:377-384.
Google Scholar
Xu X, Malave A. Protective effect of berberine on cyclophosphamide-induced haemorrhagic cystitis in rats. Pharmacol Toxicol. 2001;88:232-237.
Google Scholar
Davis L, Kuttan G. Effect of Withania somnifera on cyclophosphamide-induced urotoxicity. Cancer Lett. 2001;148:9-17.
Google Scholar
Manesh C, Kuttan G. Alleviation of cyclophosphamide-induced urotoxicity by naturally occurring sulphur compounds. J Exp Clin Cancer Res. 2002;24:509-517.
Google Scholar
Manesh C, Kuttan G. Effect of naturally occurring isothiocyanates in the inhibition of cyclophosphamide-induced urotoxicity. Phytomedicine. 2005;12:487-493.
Google Scholar
Gupta AK, ed. Review on Indian Medicinal Plants. Vol 1. New Delhi, India: (Ard-Alli)-ICMR; 2004.
Google Scholar
Zhang XF, Tan BK. Anti-diabetic property of ethanolic extract of Andrographis paniculata in streptozotocin-diabetic rats. Acta Pharmacol Sin. 2000;21:1157-1164.
Google Scholar
Kanniappan M, Mathuram LN, Natrajan R. A study of the antipyretic effect of Chiretta (Andrographis paniculata). Ind Vet J. 1991;68:314-316.
Google Scholar
Trivedi N, Rawal UM. Hepatoprotective and toxicological evaluation of Andrographis paniculata on severe liver damage. Ind J Pharmacol. 2000;32:288-293.
Google Scholar
Madav S, Tripathi HC, Tandon SK, Mishra SK. Analgesic, antipyretic and antiulcerogenic effects of andrograpgholide. Ind J Pharmaceut Sci. 1994;57:121-125.
Google Scholar
Shen YC, Chen CF, Chiou WF. Andrographolide prevents oxygen radical production by human neutrophils: possible mechanism(s) involved in its anti-inflammatory effect. Br J Pharmacol. 2002;2:399-406.
Google Scholar
Handa SS, Sharma A. Hepatoprotective activity of andrographolide from Andrographis paniculata against carbon tetrachloride. Ind J Med Res. 1990;92:276-283.
Google Scholar
Moron MA, De Pierre JW, Mannerrick B. Levels of glutathione-s-transferase activities in rat liver. Biochem Biophys Acta. 1979;582:67-68.
Google Scholar
Lowry OH, Rosenbrough NJ, Farr AL. Protein measurement with the folin phenol reagent. J Biol Chem. 1951;193:265-275.
Google Scholar
Markus L, Jorg AK, Ralph AR. Immunostimulatory effects of low dose cyclophosphamide are controlled by inducible nitric oxide synthase. Cancer Res. 2005;12:5027-5030.
Google Scholar
Berrigan MJ, Marinello AJ, Pavelic ZP, Williams CJ, Struck RF, Gurtoo HL. Protective role of thiols in cyclophosphamide-induced urotoxicity and depression of hepatic drug metabolism. Cancer Res. 1982;42:3688-3695.
Google Scholar
Ozcan A, Korkmaz A, Oter S, Coskun O. Contribution of flavonoid antioxidants to the protective effect of mesna in cyclophosphamide-induced cystitis in rats. Arch Toxicol. 2005; 8:461-465.
Google Scholar
Haque R, Bin-Hafeez B, Parvez S, Sayeed I, Ali M, Raisuddin S. Aqueous extract of walnut (Juglans regia L.) protects mice against cyclophosphamide-induced biochemical toxicity. Human Exp Toxicol. 2003;22:473-480.
Google Scholar
Xu X, Cubeddu LX, Malave A. Expression of inducible nitric oxide synthase in primary culture of rat smooth muscle cells by plasma from cyclophosphamide-treated rats.Eur J Pharmacol. 2001:416:1-9.
Google Scholar
McCafferty DM, Mudgett JS, Swain MG, Kubes P. Inducible nitric oxide synthase plays a critical role in resolving intestinal inflammation. Gastroenterology. 1997;112:1022-1027.
Google Scholar
Parkinson JE, Mitrovic B, Merrill JE. The role of nitric oxide in multiple sclerosis. J Mol Med. 1997;75:174-186.
Google Scholar
Bagasra O, Michaels FH, Zheng YM, et al. Activation of inducible form of nitric oxide synthase in the brain of patients with multiple sclerosis. Proc Natl Acad Sci U S A. 1995;92:12041-12045.
Google Scholar
Zhang H, Chen X, Teng X, Snead C, Catravas JD. Molecular cloning and analysis of the rat inducible nitric oxide synthase gene promoter in aortic smooth muscle cells. Biochem Pharmacol. 1998;55:1873-1880.
Google Scholar
Busse R, Mulsch A. Induction of nitric oxide synthase by cytokines in vascular smooth muscle cell. FEBS Lett. 1990; 275:87-90.
Google Scholar
Galea E, Feinstein DL, Reis DJ. Induction of calcium-independent nitric oxide synthase activity in primary rat glial cultures.Proc Natl Acad Sci U S A. 1992;89:10945-10949.
Google Scholar
Kaprowski H, Zheng YM, Heber-Katz E, et al. In vivo expression of nitric oxide synthase in experimentally induced neurological disease. Proc Natl Acad Sci U S A. 1993;90:3024-3027.
Google Scholar
Souza-Filho MVP, Lima MVA, Pompeu MML, Ballejo G, Cunha FQ, Ribeiro RA. Involvement of nitric oxide in the pathogenesis of cyclophosphamide-induced hemorrhagic cystitis. Am J Pathol. 1997;150:247-256.
Google Scholar
Batkhuu J, Hattori K, Takano F, Fushiya S, Oshiman K, Fujimiya Y. Suppression of NO production in activated macrophages in vitro and ex vivo by neoandrographolide isolated from Andrographis paniculata. Biol Phar Bull. 2002;9: 1169-1174.
Google Scholar

Cite article

Cite article

Cite article

OR

Download to reference manager

If you have citation software installed, you can download article citation data to the citation manager of your choice

Share options

Share

Share this article

Share with email
EMAIL ARTICLE LINK
Share on social media

Share access to this article

Sharing links are not relevant where the article is open access and not available if you do not have a subscription.

For more information view the Sage Journals article sharing page.

Information, rights and permissions

Information

Published In

Volume 5, Issue 3
Pages: 244 - 251
Article first published: September 2006
Issue published: September 2006

Keywords

  1. Andrographis paniculata
  2. andrographolide
  3. cyclophosphamide
  4. urothelial toxicity
  5. MESNA
  6. cytokines

Rights and permissions

Request permissions for this article.
PubMed: 16880430

Authors

Affiliations

K. Sheeja, MSc
Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India, [email protected]
View all articles by this author
Girija Kuttan, PhD
Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India.
View all articles by this author

Metrics and citations

Metrics

Journals metrics

This article was published in Integrative Cancer Therapies.

VIEW ALL JOURNAL METRICS

Article usage*

Total views and downloads: 614

*Article usage tracking started in December 2016

Altmetric

See the impact this article is making through the number of times it’s been read, and the Altmetric Score.
Learn more about the Altmetric Scores


Articles citing this one

Receive email alerts when this article is cited

Web of Science: 27 view articles Opens in new tab

Crossref: 29

  1. Natural products as IL‐6 inhibitors for inflammatory diseases: Synthet...
    Go to citation Crossref Google Scholar
  2. Immunomodulatory Effects of Microcin C7 in Cyclophosphamide-Induced Im...
    Go to citation Crossref Google Scholar
  3. Protective effect of rosuvastatin on cyclophosphamide-induced oral tox...
    Go to citation Crossref Google Scholar
  4. Uroprotective and Hepatoprotective Potential of Anagallis arvensis aga...
    Go to citation Crossref Google Scholar
  5. The Adroitness of Andrographolide as a Natural Weapon Against Colorect...
    Go to citation Crossref Google Scholar
  6. Protection by ginseng saponins against cyclophosphamide‐induced liver ...
    Go to citation Crossref Google Scholar
  7. The Role of Adaptogens in Prophylaxis and Treatment of Viral Respirato...
    Go to citation Crossref Google Scholar
  8. Pithecellobium dulce fruit extract mitigates cyclophosph...
    Go to citation Crossref Google Scholar
  9. Adaptogens in chemobrain (Part I): Plant extracts attenuate cancer che...
    Go to citation Crossref Google Scholar
  10. Adaptogens in chemobrain (Part III): Antitoxic effects of plant extrac...
    Go to citation Crossref Google Scholar
  11. Andrographis paniculata: From Traditional to Nano Drug for Cancer Ther...
    Go to citation Crossref Google Scholar
  12. Morphological and chemical studies of artificial Andrographis panicula...
    Go to citation Crossref Google Scholar
  13. Ex-situ conservation of medicinal Plants and its therapeutic in mine i...
    Go to citation Crossref Google Scholar
  14. Andrographolide attenuates LPS-stimulated up-regulation of C-C and C-X...
    Go to citation Crossref Google Scholar
  15. Protective effect of extract of Mauremys mutica ...
    Go to citation Crossref Google Scholar
  16. Andrographis paniculata (Burm. f.) Wall. ex Nees: A Revi...
    Go to citation Crossref Google Scholar
  17. A 35kD Phyllanthus niruri protein modulates iron mediated oxidative im...
    Go to citation Crossref Google Scholar
  18. How to use the monographs
    Go to citation Crossref Google Scholar
  19. Tinospora cordifolia ameliorates urotoxic effect of cyclophosphamide b...
    Go to citation Crossref Google Scholar
  20. A bitter plant with a sweet future? A comprehensive review of an orien...
    Go to citation Crossref Google Scholar
  21. Immuno-enhancement effects of Shenqi Fuzheng Injection on cyclophospha...
    Go to citation Crossref Google Scholar
  22. Andrographolide: A New Plant-Derived Antineoplastic Entity on Horizon
    Go to citation Crossref Google Scholar
  23. Andrographolide regulates epidermal growth factor receptor and transfe...
    Go to citation Crossref Google Scholar
  24. Anti-malarial activities of Andrographis paniculata and Hedyotis corym...
    Go to citation Crossref Google Scholar
  25. Absorption of andrographolides from Andrographis paniculata and its ef...
    Go to citation Crossref Google Scholar
  26. Uroprotective Effects of Curcumin in Cyclophosphamide-Induced Haemorrh...
    Go to citation Crossref Google Scholar
  27. Protective effect of triterpenoid fractions from the rhizomes of Astil...
    Go to citation Crossref Google Scholar
  28. Synthesis of andrographolide derivatives and their TNF-α and IL-6 expr...
    Go to citation Crossref Google Scholar
  29. Hepatoprotective Effect of Andrographolide Against Hexachlorocyclohexa...
    Go to citation Crossref Google ScholarPub Med

Figures and tables

Figures & Media

Tables

View Options

View options

PDF/ePub

View PDF/ePub

Get access

Access options

If you have access to journal content via a personal subscription, university, library, employer or society, select from the options below:

Alternatively, view purchase options below:

Purchase 24 hour online access to view and download content.

Subscribe to this journal

Access journal content via a DeepDyve subscription or find out more about this option.

Start 2 week free trial
Need help?
Download PDF

Also from Sage