Genotoxic evaluation of the antimalarial drug, fansidar, in cultured human lymphocytes

Abstract

Fansidar (pyrimethamine-sulfadoxine) has been used extensively worldwide for the treatment of chloroquine resistant Plasmodium falciparum malaria, toxoplasmosis and Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. Because of the wide usage of pyrimethamine-sulfadoxine in developing countries and the lake of information from open literature and reports from manufacturers about the genotoxicity of such antimalarial drug, the present work was suggested. The possible genetic toxicity of fansidar has been evaluated in human peripheral blood lymphocyte cultures. The frequencies of sister-chromatid exchanges (SCE) and micronuclei (MN) were scored as genetic endpoints. Both tests covering a wide range of induced genetic damage as primary DNA damage, clastogenicity and aneugenicity. Cultures were set up by using blood samples from two healthy donors and the treatment was done using different fansidar concentrations ranging from 1:20 to 10:200 microg/ml. From our results, it appears that this drug is able to induce moderate genotoxic effects, as revealed by the increases found in SCE and MN frequencies in cultures from the two donors at the two highest concentrations tested (5:100 and 10:200 microg/ml). In addition, cyotoxic/cytostatic effects of fansidar were revealed by a decrease in the proliferative rate index (PRI) and in the cytokinesis block proliferation index (CBPI). Our findings suggest that the use of this drug should be restricted to situations where other antimalarial drugs cannot be used. The drug should never be given to pregnant women.

Clearance of Circulating Epstein‐Barr Virus DNA in Children with Acute Malaria after Antimalaria Treatment

“…The clearance of circulating EBV DNA after antimalaria treatment may have resulted from elimination of the parasite and from a direct effect of the drugs on B cells-Fansidar is known to inhibit lymphocyte proliferation [24]. Of note, however, in a previous study, treatment with another compound (chloroquine) reduced, in a related way, the number of circulating EBV-carrying B cells [3].…”

Antibacterial and antifungal activities of some trimethoprim salts

“…Folic acid is an essential cofactor in the biosynthesis of nucleic acids (Abou-Eisha and Afifi, 2004). Some studies demonstrate that trimethoprim is able to induce both cytotoxic and moderate genotoxic effects in cultured human lymphocytes; these cytogenetic effects being compatible with the role of folate in DNA metabolism (Abou-Eisha et al, 1999).…”

Chromosomal Disturbances during Mitotic Activity of Root Tip Cells in Allium by Certain Commonly Used Antibiotics

“…The use of the drug (fansidar a combination of Sulfadoxine-pyrimethamine) against resistant P. falciparum reported the cyto-genotoxic effects (micronucleus and sister chromatid exchange induction) of the drug on cultured human lymphocytes. 36 Dapsone is used for the treatment of leprosy, dermatitis herpetiformis. 37 The combination (Dapson+pyrimethamine) used for malaria treatment.…”