Toxicopathologic Effects of Artemisinin in Broiler Chickens Following a Single Oral Dose: An LD50 Study


Authors

  • H.A. Arab Department of Pharmacology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
  • S.H. Mardjanmehr Department of Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
  • A. Shahbazfar Department of Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
  • A. Rassouli Department of Pharmacology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
  • M. Abdollahi Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Science, Tehran, Iran
  • O. Nekouie Department of Food Hygiene and Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

DOI:

https://doi.org/10.3923/ijps.2009.808.812

Keywords:

Artemisinin, broilers, neurotoxicity, single dose, toxicopathology

Abstract

The present study aimed to find LD50 of artemisinin and to characterize the single dose toxicity of the drug following oral exposure. 49 day-old Ross broilers divided into 7 groups; one control, one drug vehicle and five treatment groups. The treatment groups received artemisinin alcoholic solution at doses of 10, 50, 250, 1250 and 2500 mg/kg on day 30 by a crop tube. The control and drug vehicle groups received normal saline and ethyl alcohol, respectively. In the period of study just in 1250 and 2500 mg/kg groups there were a few transient neurological signs like depression and unconsciousness. These signs were also observed in drug vehicle group. None of the birds died, so they were euthanised on day 40. In microscopic examination, only in treatment groups a slight degeneration in liver and kidney as intracytoplasmic eosinophilic inclusions, hepatocellular swelling and bile retention in liver were evident. In brain central chromatolysis, scattered neuronal necrosis, spongy change and focal axonal swelling were observed. It is concluded that artemisinin has a good margin of safety in poultry but in very high doses it may cause some adverse effects.

References

Allen, P.C., J. Lydon and H.D. Danforth, 1997. Effects of components of Artemisia annua on coccidia infections in chickens. Poult. Sci., 76: 1156-1163.

Arab, H.A., S. Rahbari, A. Rassouli, M.H. Moslemi and F. Khosravirad, 2006. Determination of artemisinin in Artemisia sieberi and anticoccidial effects of the plant extract in broiler chickens. Trop. Anim. Health Prod., 38: 497-503.

Brewer, T.G., S.J. Grate, J.O. Peggins, P.J. Weina and J.M. Petras et al., 1994. Fatal neurotoxicity of arteether and artemether. Am. J. Trop. Med. Hyg., 51: 251-259.

Brewer, T.G., J.O. Peggins, S.J. Grate, J.M. Petras and B.S. Levine et al., 1994. Neurotoxicity in animals due to arteether and artemether. Trans. R. Soc. Med. Hyg., 88: 33-36.

China Cooperative Research Group, 1982. Studies on the toxicity of quinghaosu and its derivatives. China Cooperative Research Group on qinghaosu and its derivatives as antimalarials. J. Tradit. Chinese Med., 2: 31-38.

Dien, T.K., D.E. Vries, P.J. Xuan-Khanh, N. Koopmans and R. Binh et al., 1997. Effect of food intake on pharmacokinetics of oral artemisinin in healthy vietnamese subjects. Antimicrob. Agents Chemother., 41: 1069-1072.

Fishwick, J., W.G. Mclean, G. Edwards and S.A. Ward, 1995. The toxicity of artemisinin and related compounds on neuronal and glial cells in culture. Chem. Biol. Interact., 96: 263-271.

Genovse, R.F., D.B. Newman, Q. Li , J.O. Peggins and T.G. Brewer, 1998. Dose-dependent brainstem neuropathology following repeated arteether administration in rats. Brain Res. Bull., 45: 199-202.

Genovese, R.F., J.M. Petras and T.G. Brewer, 1995. Arteether neurotoxicity in the absence of deficits in behavioural performance in rats. Ann. Trop. Med. Parasitol., 89: 447-449.

Gordi, T. and E.I. Lepist, 2004. Artemisinin derivatives: Toxic for laboratory animals, safe for humans? Toxicol. Lett., 147: 99-107.

Kamchonwongpaisan, S., P. McKeever, P. Hossler, H. Ziffer and S.R. Meshnick, 1997. Artemisinin neurotoxicity: Neuropathology in rats and mechanistic studies in vitro. Am. J. Trop. Med. Hyg., 56: 7-12.

Kaptein, S.J.F., T. Efferth, M. Leis, S. Rechter and S. Auerochs et al., 2006. The anti-malaria drug artesunate inhibits replication of cytomegalovirus in vitro and in vivo. Antiviral Res., 69: 60-69.

Li, Q., L.H. Xie, T.O. Johnson, Y. Si, A.S. Haeberle and P.J. Weina, 2007. Toxicity evaluation of artesunate and artelinate in Plasmodium berghei infected and uninfected rats. Trans. R. Soc. Trop. Med. Hyg., 101: 104-112.

Nontprasert, A., S. Pukrittayakamee, A.M. Dondorp, R. Clemens, S. Looareesuvan and N.J. White, 2002. Neuropathologic toxicity of artemisinin derivatives in a mouse model. Am. J. Trop. Med. Hyg., 67: 423-429.

Nontprasert, A., S. Pukrittayakamee, M. Nosten-Bertrand, S. Vanijanonta and N.J. White, 2000. Studies of the neurotoxicity of oral artemisinin derivatives in mice. Am. J. Trop. Med. Hyg., 62: 409-412.

Peys, E., J. Vandenkerchhove, J. van Hemel and B. Sas, 2006. Intermediate-term toxicity of repeated orally administered doses of the antimalarial β-artemether in dogs. Exp. Toxicol. Pathol., 57: 299-304.

Price, R., M. van Vugt, L. Phaipun, C.H. Luxemburger and J. Simpson et al., 1999. Adverse effects in patients with acute falciparum malaria treated with artemisinin derivatives. Am. J. Trop. Med. Hyg., 60: 547-555.

Schmuck, G., E. Roehrdanz, R.K. Haynes and R. Kahl, 2002. Neurotoxic mode of action of artemisinin. Antimicrob. Agents Chemother., 46: 821-827.

Sen, R., S. Bandyopadhyay, A. Dutta, G. Mandal, S. Ganguly, P. Saha and M. Chatterjee, 2007. Artemisinin triggers induction of cell-cycle arrest and apoptosis in Leishmania donovani promastigotes. J. Med. Microbiol., 56: 1213-1216.

Shuhua, X., Y. Yanqing, Y. Qiqing, J. Utzinger and G. Huifang et al., 2002. Potential long-term toxicity of repeated orally administered doses of artemether in rats. Am. J. Trop. Med. Hyg., 66: 30-54.

Singh, N.P. and H.C. Lai, 2004. Artemisinin induces apoptosis in human cancer cells. Anticancer Res., 24: 2277-2280.

Smith, S.L., J. Fishwick, W.G. McLean, G. Edwards and S.A. Ward, 1997. Enhanced in vitro neurotoxicity of artemisinin derivative in the presence of haemin. Biochem. Pharmacol., 53: 5-10.

Smith, S.L., J.I. Maggs, G. Edwards, S.A. Ward, B.K. Park and W.G. McLean, 1998. The role of iron in neurotoxicity: A study of novel antimalarial drugs. Neurotoxicology, 19: 557-559.

Smith, S.L., C.J. Sadler, C.C. Dodd, G. Edwards, S.A. Ward, B.K. Park and W.G. McLean, 2001. The role of glutathione in the neurotoxicity of artemisinin derivatives in vitro. Biochem. Pharmacol., 61: 409-416.

Wesche, D., M.A. Decoster, F.C. Tortella and T.G. Brever, 1994. Neurotoxicity of artemisinin analogs in vitro. Antimicrob. Agents Chemother., 38: 1813-1819.

Zhao, Y., 1985. Studies on systemic pharmacological effects of artesunate. J. Trop. Med. Hyg., 88: 391-396.

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Published

2009-07-15

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Section

Research Article

How to Cite

Arab, H., Mardjanmehr, S., Shahbazfar, A., Rassouli, A., Abdollahi, M., & Nekouie, O. (2009). Toxicopathologic Effects of Artemisinin in Broiler Chickens Following a Single Oral Dose: An LD50 Study. International Journal of Poultry Science, 8(8), 808–812. https://doi.org/10.3923/ijps.2009.808.812