Neurobehavioral and biochemical responses to artemisinin-based drug and aflatoxin B1 co-exposure in rats.

Abstract

Populations in malaria endemic areas are frequently exposed to mycotoxin-contaminated diets. The possible toxicological outcome of co-exposure to dietary aflatoxin B₁ (AFB₁) and artemisinin-based combination therapy warrants investigation to ascertain amplification or attenuation of cellular injury. Here, we investigated the neurobehavioral and biochemical responses associated with co-exposure to anti-malarial drug coartem, an artemether-lumefantrine combination (5 mg/kg body weight, twice a day and 3 days per week) and AFB₁ (35 and 70 µg/kg body weight) in rats. Motor deficits, locomotor incompetence, and anxiogenic-like behavior induced by low AFB₁ dose were significantly (p < 0.05) assuaged by coartem but failed to rescue these behavioral abnormalities in high AFB₁-dosed group. Coartem administration did not alter exploratory deficits typified by reduced track plot densities and greater heat map intensity in high AFB₁-dosed animals. Furthermore, the reduction in cerebral and cerebellar acetylcholinesterase activity, anti-oxidant enzyme activities, and glutathione and thiol levels were markedly assuaged by coartem administration in low AFB₁ group but not in high AFB₁-dosed animals. The significant attenuation of cerebral and cerebellar oxidative stress indices namely reactive oxygen and nitrogen species, xanthine oxidase activity, and lipid peroxidation by coartem administration was evident in low AFB₁ group but not high AFB₁ dose. Although coartem administration abated nitric oxide level, activities of myeloperoxidase, caspase-9, and caspase-3 in animals exposed to both doses of AFB₁, these indices were significantly higher than the control. Coartem administration ameliorated histopathological and mophometrical changes due to low AFB₁ exposure but not in high AFB₁ exposure. In conclusion, contrary to AFB₁ alone, behavioral and biochemical responses were not altered in animals singly exposed to coartem. Co-exposure to coartem and AFB₁ elicited no additional risk but partially lessened neurotoxicity associated with AFB₁ exposure.