Role of NRF2 and Caspase 3 in the Cerebrum of Nickel Chloride-Exposed Wistar Rats Following Pretreatment with Selenium

Abstract

Background: Nickel is recognized as an environmental pollutant and heavy metal known to have harmful effects on the nervous system. Conversely, selenium, a crucial trace element with strong antioxidant properties, has shown promise in mitigating the toxic effects of heavy metals. Accordingly, this study examined selenium's protective effects against Nickel chloride (NiCl₂)-induced cerebral toxicity in adult Wistar rats.

Methods: A total of forty-two rats were randomly divided into six groups namely: I- control; II- NiCl₂ (5 mg/kg body weight); III- Selenium (0.25 mg/kg) + NiCl₂; IV- Selenium (0.5 mg/kg) + NiCl₂; V- Selenium (0.25 mg/kg), and VI- Selenium (0.5 mg/kg). At the end of the experiment, neurobehavior, antioxidant enzymes, lipid peroxidation, histology, and gene expression of NRF2 and caspase-3 were evaluated.

Results: NiCl₂ exposure significantly impaired antioxidant enzymes activity, and cognition and downregulated the expression of NRF2 in the cerebrum. Also, increased lipid peroxidation, upregulation of caspase-3, and altered morphology of the cerebrum were observed following treatment with NiCl₂. However, pretreatment of NiCl₂-exposed rats with selenium attenuated these adverse effects.

Conclusion: Taken together, selenium could be useful as a neuroprotective agent against NiCl₂ toxicity.