Effects of primaquine and chloroquine on oxidative stress parameters in rats.

Francianne Giovanella,Emilio L Streck,Lara M Gomes,Monique Michels,Samira D.T De Prá,Giselli Scaini,Milena Carvalho-Silva,Renata C Gonçalves,Ana Luiza Dajori,Gabriela K Ferreira,Renan P De Souza,Felipe Dal-Pizzol,Vanessa M Andrade,Luiza M Longaretti,Letícia S Galant

doi:10.1590/0001-3765201520140637

Abstract

Primaquine and chloroquine are used for the treatment of malaria; evidence from the literature suggests that these drugs may induce oxidative stress. In this study we investigated the effects of primaquine and chloroquine on oxidative damage and DNA damage in brain, liver and kidney of rats after 7, 14 and 21 days of administration. Our results demonstrated that primaquine causes DNA damage in brain after 7, 14 and 21 days, and in liver after 7 and 14 days. Moreover, primaquine increases TBARS levels in the kidney and protein carbonyls in the brain after 14 days, and decreases protein carbonyls in the liver after 7 days. Whereas chloroquine causes DNA damage in the kidney after 7 and 14 days, and in the liver after 14 and 21 days, increases TBARS levels in the kidney after 7 days, and decreases TBARS levels in the brain after 21 days. Moreover, decreases protein carbonyls in the liver after 7 and 14 days, and in the brain after 7 and 21 days. However, chloroquine treatment for 14 days increases protein carbonyls in the brain and kidney. In conclusion, these results showed that prolonged treatment with antimalarial may adversely affect the DNA.

Highlights

Malaria is a life-threatening parasitic disease of epidemic proportions caused in humans by parasites of the Plasmodium species through the bite of infected anopheles mosquitoes, and it is a majorAn Acad Bras Cienc (2015) 87 (2 Suppl.)1998, WHO 2013), and the severity of malaria is exacerbated by resistant strains of Plasmodium and lack of effective vaccines and drugs (NaBangchang and Karbwang 2009).Malaria control requires an integrate approach, including prevention and prompt treatment with effective antimalarials (Staines and Krishna 2012)
Our results demonstrated that 7 and 14 days of PQ administration increase DNA damage frequency and index in brain and liver (Figures 1 and 2, respectively), whereas 21 days of PQ administration increased DNA damage frequency and index only in brain (Figure 3)
21 days of CQ treatment decreased Thiobarbituric acid reactive species (TBARS) levels in brain, while the TBARS levels were not altered in the liver after CQ and PQ treatment (Figure 4)

Summary

Introduction

Malaria is a life-threatening parasitic disease of epidemic proportions caused in humans by parasites of the Plasmodium species through the bite of infected anopheles mosquitoes, and it is a majorAn Acad Bras Cienc (2015) 87 (2 Suppl.)1998, WHO 2013), and the severity of malaria is exacerbated by resistant strains of Plasmodium and lack of effective vaccines and drugs (NaBangchang and Karbwang 2009).Malaria control requires an integrate approach, including prevention (primarily vector control) and prompt treatment with effective antimalarials (Staines and Krishna 2012). Primaquine (PQ) and chloroquine (CQ) are the two widely used antimalarials in the tropical regions of the world (Thabrew et al 1985, WHO 2013). These drugs are used for the treatment of malaria and for the prevention and prophylaxis, as well as for treatment of other diseases (Leslie 1990). These drugs belong to the quinoline group, their mode of action and the stage of Plasmodium at which they act differs. One common property of the two drugs is that they accumulate in the Plasmodium and the cells, which harbor the parasite (De Duve et al 1974, Foley and Tilley 1998)

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Conclusion