Genotoxicity and carcinogenicity of ivermectin and amoxicillin in vivo systems.

Antiparasitic substances are chemicals used to control or kill endoparasites and ectoparasites. Based on the premise that Ivermectin (IVM) and Amoxicillin (AMX) are commonly considered in parasitic control in mammals, the present study aimed to evaluate the carcinogenic and genotoxic potential of different concentrations of IVM and AMX through the detection of epithelial tumor test in Drosophila melanogaster. Third-instar larvae descending from the cross between wts/TM3, Sb1 females and mwh/mwh males were treated with different concentrations of IVM (2.9, 5.8, 11.6 and 23.2 x 10-17 mM) or AMX (1.37, 2.74, 5.48 and 10.9 x 10-16mM). The results revealed that IVM increased the frequency of epithelial tumor in D. melanogaster considering all evaluated concentrations, while AMX showed no carcinogenic effect. Furthermore, the Micronucleus (MN) test in Tradescantia pallida was used to evaluate the genotoxic effect of IVM and AMX. T. pallida individuals were exposed for 8 hours at different concentrations of IVM (5.71, 11.42, 22.84 and 45.68 x 10-5mM) or AMX (5.13, 10.26, 20.52 and 41.05 x 10-3mM). Findings showed an increase in the frequency of micronuclei in T. pallida treated with 11.42, 22.84 and 45.68 x 10-5mM of IVM. We conclude that chronic exposure to IVM is directly associated with events resulting from genetic instability (genotoxicity and carcinogenicity). On the other hand, AMX was neither carcinogenic nor genotoxic for D. melanogaster and T. pallida.

Mikania glomerata Sprengel (Asteraceae) influences the mutagenicity induced by doxorubicin without altering liver lipid peroxidation or antioxidant levels.

As shown in numerous studies, natural compounds may exert adverse effects, mainly when associated with some drugs. The hydroalcoholic extract of Mikania glomerata is the pharmaceutical form present in commercially available syrup used for the treatment of respiratory diseases in popular Brazilian medicine. The objective of the present investigation was (1) to evaluate the preventive effects of standardized hydroalcoholic extract of M. glomerata (MEx) against antitumoral drug doxorubicin (DXR)-induced micronucleated polychromatic erythrocytes (MNPCE) in a subchronic assay in mice, and (2) to determine the liver content of malondialdehyde (MDA) and the antioxidants glutathione (GSH) and vitamin E (VE). Male Swiss mice were treated for 30 d with MEx added to drinking water, combined or not with DXR (90 mg/kg body weight) injected intraperitoneally (ip) 24 h before analysis. The results demonstrated that MEx produced no genotoxic damage, but significantly increased the frequency of MNPCE induced by DXR, indicating a drug-drug interaction. This rise was not accompanied by lipid peroxidation or antioxidants level reduction, as measured by MDA, GSH, and VE. Despite the presence of coumarin (a known antioxidant), MEx may exert adverse effects probably in association with mutagenic compounds, although this effect on DNA damage did not involve oxidative stress.