Females are more susceptible than male mice to thermal hypernociceptive behavior induced by early-life bisphenol-A exposure: Effectiveness of diphenyl diselenide

Humans are ubiquitously exposed to bisphenol A (BPA), one of the most used synthetic monomers for manufacturing polycarbonate plastics. BPA exposure leads to abnormal nociceptive perception and neuroinflammation in rodents. This study investigated whether diphenyl diselenide (PhSe)(2), a pleiotropic selenium-containing molecule, would be effective against the hypernociceptive behavior induced by the early-life BPA exposure to mice. Three-week-old male and female Swiss mice received intragastrically BPA (5 mg/kg) from 21st to 60th postnatal day. After, the mice received by the intragastric route (PhSe)(2) (1 mg/kg) once a day for seven days. After the last day of treatment, the mice performed the hot plate and tail immersion tests. The cerebral cortex samples were used to determine the levels of proteins related to apoptosis and inflammation. The results demonstrated that females were more susceptible than male mice to thermal hypernociception induced by early-life exposure to BPA. (PhSe)(2) was effective against the reduction in the latency to paw and tail withdrawal induced by BPA exposure in female mice. Furthermore, (PhSe)(2) restored the impairment in the levels of inflammatory proteins (COX-2, IL-1 beta, and p-JNK/JNK) but not those of apoptosis in the cerebral cortex of female mice exposed to BPA. Collectively, these data showed that females were more susceptible to thermal hypernociceptive behavior induced by early-life exposure to BPA than male mice. The administration of (PhSe)(2) reduced thermal hypernociceptive behavior, a sex independent effect, in BPA-exposed mice. (PhSe)(2) modulated inflammatory protein levels in the cerebral cortex of female mice exposed to BPA.