DOI QR코드

DOI QR Code

Study of Kidney Toxicity of Azadirachta Indica Extract for Oral Administration in Rats

님추출물의 경구투여에 따른 랫드의 신장독성 연구

  • Received : 2013.12.05
  • Accepted : 2014.03.26
  • Published : 2014.06.30

Abstract

BACKGROUND: Azadirachta indica has been widely used as environment-friendly organic materials because of its insecticidal properties. This study was carried out to investigate the acute toxicity and the subacute toxicity of Azadirachta indica extract(AIE) in rats. METHODS AND RESULTS: For the oral acute toxicity test, Sprague-Dawley rats were gavaged with 2.0 g/Kg bw of AIE. The $LD_{50}$ value was greater than 2.0 g/Kg bw for both male and female rats. For the subacute toxicity study, rats were treated with AIE at doses of 0.5, 1.0, 2.0 mg/Kg bw once a day for 4 weeks(n=10 animals per each group). There were no significant changes in body weight, food intake and water consumption observed during the experimental duration. In addition, no difference of relative kidney weight was observed among all treated groups. Serum creatinine level in the AIE 2.0 g/Kg group increased significantly compared with that of control group in male rats, but serum blood urea nitrogen was significantly decreased in a dose-dependent manner (p<0.05). Significant increase of serum cholesterol levels were observed in all AIE groups, compared with the control group, in the female rats (p<0.05). However, histopathological examination of the kidney did not reveal any significant lesions in all groups. CONCLUSION: On the basis of results, it could be concluded that oral administration AIE didn't cause any toxic response in kidney, except the increased serum cholesterol.

Keywords

Azadirachta indica extract;Kidney;Subacute toxicity

References

  1. Selim, M.E., Yousef, O.M., Hamid, S.H., Aleisa, N.A., 2013. Hyperlipidemia aggravated renal disease in bacteremic male albino rats, J. Med. Sci. 1, 9-22.
  2. Raizada, R.B., Srivastava, M.K., Kaushal, R.A., Singh, R.P., 2001. Azadirachtin, a neem biopesticide: subchronic toxicity assessment in rats. Food and Chemical Toxicology 39, 477-483. https://doi.org/10.1016/S0278-6915(00)00153-8
  3. Singh, P.P., Junnarkar, A.Y., Thomas, G.P., Tripathi, R.M., Varma, R.K., 1990. A pharmacological study of Azadirachta indica, Fitoterapia 61, 164-168.
  4. Ray, A., Banerjee, B.D., Sen, P., 1996. Modulation of humoral and cell-mediated immune responses by Azadirachta indica (Neem) in mice, Indian J. Exp. Biol. 34, 698-701.
  5. Kumar, G.H., Priyadarsini, R.V., Vinothini, G., Letchoumy, P.V., Nagini, S., 2010. The neem limonoids azadirachtin and nimbolide inhibit cell proliferation and induce apoptosis in an animal model of oral oncogenesis, Invest New Drugs. 4, 392-401.
  6. Ezz-Din, D., Gabry, M.S., Farrag, A.R.H., Abdel Moneim, A.E., 2011. Physiological and histological impact of Azadirachta indica (neem) leaves extract in a rat model of cisplatin-induced hepato and nephrotoxicity, J. Med. Plants Res. 5, 5499-5506.
  7. Han, S.B., Kim, J.H., 2013. Research trend of neem based biopesticides, Korean J. Pestic. Sci. 17, 220-230. https://doi.org/10.7585/kjps.2013.17.3.220
  8. Koner, B.C., Banerjee, B.D., Ray, A., 1997. Effects of stress on gamma glutamyl transpeptidase (GGT) activity in lymphoid system of rats: modulation by drugs, Indian J. Exp. Biol. 35, 222-224.
  9. Lee, J.W., Jin, C.L., Jang, K.C., Choi, G.H., Lee, D., Kim, J.H., 2013. Investigation on the insecticidal limonoid content of commercial biopesticides and neem extract using solid phase extraction, J. Agric. Chem. Environ. 2, 81-85.
  10. Gandhi, M., Lal, R., Sankaranarayanan, A., Banerjee, C.K., Sharma, P.L., 1988. Acute toxicity study of the oil from Azadirachta indica seed (neem oil), J. Ethnopharmcol. 23, 39-51. https://doi.org/10.1016/0378-8741(88)90113-4
  11. Garg, S., Taluja, V., Upadhyay, S.N., Talwar, G.P., 1993. Studies on the contraceptive efficacy of praneem polyherbal cream, Contraception. 48, 596-591.
  12. Parshad, O., Singh, P., Gardner, M., Fletcher, C., Rickards, E., Choo-Kang, E., 1994. Effect of aqueous neem (Azadirachta indica) extract on testosterone and other blood constituents in male rats. A pilot study, West Indian Med. J. 43, 71-74.
  13. Rahman, M.F., Siddiqui, M.K.J., Jamil, K., 2001. Effects of vepacide (Azadirachta indica) on aspartate and alanine aminotransferase profiles in a subchronic study with rats, Hum. Exp. Toxicol. 20, 243-249. https://doi.org/10.1191/096032701678227730
  14. Rahman, M.F., Siddiqui, M.K.J., Jamil, K., 2002. LDH profiles of male and female rats treated with vepacide, Phytother. Res. 16, 122-126. https://doi.org/10.1002/ptr.809
  15. Cheesbrough, M., 1991. Medical Laboratory Manual for Tropical Countries, pp. 133-160, 2nd ed. University Press, Cambridge, Great Britain.
  16. Bandyopadhyay, U., Biswas, K., Sengupta, A., Moitra, P., Dutta, P., Sarkar, D., Debnath, P., Ganguly, C.K., Banerjee, R.K., 2004. Clinical studies on the effect of Neem (Azadirachta indica) bark extract on gastric secretion and gastroduodenal ulcer, Life Sci. 75, 2867-2878. https://doi.org/10.1016/j.lfs.2004.04.050
  17. Biswas, K., Chattopadhyay, I., Banerjee, R. K., Bandyopadhyay, U., 2002. Biological activities and medicinal properties of neem (Azadirachta indica), Indian Acad. Sci. 82, 1336-1345.
  18. Kaysan, G.A., 2007. Hyperlipidemia in chronic kidney disease, Int. J. Artif. Organs 30, 987-992. https://doi.org/10.1177/039139880703001107
  19. Choi, H. S., Wu, X. Y., Kim, W. S., Lee, Y., Choi, B. M., Kuk, Y. I., 2011. Effects of organic materials on insect and disease occurrence and fruit quality in pear orchards, Korean J. Org. Agric. 19, 405-416.
  20. Das, B.K., Mukherjee, S.C., Murjani, O., 2002. Acute toxicity of neem (Azadirachta indica) in Indian major carps, J. Aquac. Trop. 17, 23-33.
  21. Das, B.K., Mukherjee, S.C., Sahu, B.B., Murjani, G., 1999. Neem (Azadirachta indica) extract as an antibacterial agent against fish pathogenic bacteria, Indian J. Exp. Biol. 37, 1097-1100.
  22. Deng, Y.X., Cao, M., Shi, D.X., Yin, Z.Q., Jia, R.Y., Xu, J., Wang, C., Lv, C., Liang, X.X., He, C.L., Yang, Z.R., Zhao, J., 2013. Toxicological evaluation of neem (Azadirachta indica) oil: acute and subacute toxicity, Environ. Toxicol. Pharmacol. 35, 240-246. https://doi.org/10.1016/j.etap.2012.12.015
  23. Dhaliwal, P.K., Roop, J.K., Guraya, S.S., Dhawan, A.K., 1998. Antifertility activity of neem-seed oil in cyclic female rats, in: Dhaliwal, P.K., Randhawa, N.S., Arora, A. and Dhawan, A.K. (Eds), Ecological agriculture and sustainable development, Center for Research in Rural & Industrial Development, Ludhiana, India. pp. 340-346.
  24. EFSA (European Food Safety Authority), 2011. Conclusion on the peer review of the pesticide risk assessment of the active substance azadirachtin, EFSA J. 9, 1858. https://doi.org/10.2903/j.efsa.2011.1858
  25. Abdel Megeed, M.I., Radwan, U.M., Hindy, A.Z., El Zarook, A., 2001. Liver functions under stress of certain common pesticides residue used on fruits and vegetables orally administrated, Annals Agric. Sci. 46, 383-404.
  26. Alam, M.M., Siddiqui, M.B., Husain, W., 1990. Treatment of diabetes through herbal drug in rural India, Fitoterapia 61, 240-242.
  27. Ashafa, A.O.T., Orekoya, L.O., Yakuba, M.T., 2012. Toxicity profile of ethanolic extract of Azadirachta indica stem bark in male Wistar rats, Asian Pac. J. Trop. Biomed. 2, 811-817. https://doi.org/10.1016/S2221-1691(12)60234-2

Cited by

  1. Effects of Aqueous Azadirachta indica Extract on Hepatotoxicity in Rats vol.33, pp.4, 2014, https://doi.org/10.5338/KJEA.2014.33.4.395
  2. Evaluation of 3-week Repeated Dose Oral Toxicity on Amomum tsao-ko Extract in Balb/c Mice vol.58, pp.2, 2015, https://doi.org/10.3839/jabc.2015.024

Acknowledgement

Grant : Research Program for Agricultural Science & Technology Development

Supported by : National Academy of Agricultural Science