Dietary aflatoxin B1 and antimalarial-a lumefantrine/artesunate-therapy perturbs male rat reproductive function via pro-inflammatory and oxidative mechanisms.

We investigated the impact of Coartem™ (COA) and aflatoxin B1 (AFB) on rats' hypothalamus, epididymis, and testis. Male rats were randomly grouped (n = 5 rats) and treated: control group (corn oil), AFB (70 µg/kg), COA (5 mg/kg), COA + AFB (5 + 0.035 mg/kg) and COA + AFB (5 + 0.07 mg/kg) for 28 days. Blood samples were collected for serum prolactin, testosterone, follicle-stimulating and luteinising hormones (FSH and LH) assay upon sacrifice. The semen, hypothalamus, epididymis, and testes were harvested for morphological, biochemical, and histopathology determination of oxidative, inflammation stress, genomic integrity, and pathological alterations. Exposure to the COA and AFB caused the cauda epididymal spermatozoa to display low motility, viability, and volume, with increased abnormalities. Hormonal disruption ensued in animals exposed to COA and AFB alone or together, exemplified by increased prolactin, and decreased testosterone, FSH and LH levels. Treatment-related reduction in biomarkers of testicular metabolism-acid and alkaline phosphatases, glucose-6-phosphate dehydrogenase, and lactate dehydrogenase-were observed. Also, COA and AFB treatment caused reductions in antioxidant (Glutathione and total thiols) levels and antioxidant enzyme (Catalase, superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase) activities in the examined organs. At the same time, treatment-related increases in DNA damage (p53), oxidative stress (xanthine oxidase, reactive oxygen and nitrogen species and lipid peroxidation), inflammation (nitric oxide and tumour necrosis factor-alpha), and apoptosis (caspase-9, and -3) were observed. Chronic exposure to COA and AFB1 led to oxidative stress, inflammation, and DNA damage in male rats' hypothalamic-reproductive axis, which might potentiate infertility if not contained.