Exposure to intranasal chromium triggers dose and time-dependent behavioral and neurotoxicological defects in rats.

ABSTRACT

The extensive recorded environmental and occupational dispersal of hexavalent chromium (CrVI) dust contributes to an increased interest in its toxicological consequences. A previous study of our team described a brain injury induced by acute intranasal instillation of Cr(VI) in rats, which was characterized by oxidative stress and inflammation. This proposed a high risk of brain damage among Cr(VI) exposed individuals either environmentally or occupationally especially through the nasal cavity. Accordingly, the main aim of this study was to evaluate the effects of subacute/subsubacute/subchronic exposure to intranasal potassium dichromate (inPDC) solution in three dose levels (0.125, 0.25, or 0.5 mg/kg/day for five successive days/week) for 3 different intervals/dose two weeks, one month, and two months, on the brain of rats. The rats were sacrificed 24 h following the last inPDC dose. The locomotor activity, motor coordination, and object recognition behavior of the rats have been measured. Evaluation of oxidative stress; evidenced by lipid peroxidation and reduced glutathione, and inflammatory markers; evidenced by interleukin 1-beta in the brain tissues, as well as the brain PI3K and PKB contents were performed. Furthermore, the brain anti-glial fibrillary acidic protein (GFAP); marker of neurotoxicity was assessed immunohistochemically. Brain histopathological alterations were also studied. The findings of the current study revealed a dose- and time-dependent inPDC-induced brain toxicity in rats, as displayed by the biochemical, immunohistochemical and histopathological evaluation. Behaviorally, the major toxic effects of inPDC were observed on the locomotor and cognition functions, however, minor effects were observed on the motor coordination. The results suggest that short-term exposure to intranasal Cr(VI), in theses doses, does not trigger a major brain injury in rats; however, observation of more toxic alterations in a time-dependent manner is a threat of more sever toxicity upon longer exposure.