Background: Cadmium (Cd) and bisphenol A (BPA) are known industrial additives and
environmental toxicants that have been extensively reported for their various deleterious effects
on biological systems, particularly endocrine disruption and neurotoxicity. In high‑fat diet‑induced
insulin‑resistant model rats, we studied the neurotoxicity and oxidative stress effects of co‑exposure to
Cd and BPA. Aims: This study aims to look at prefrontal microarchitecture and antioxidant profiles in
insulin‑resistant rats. Materials and Methods: Twenty‑five adult Wistar rats were randomly assigned
into five groups (A– E; n = 5). With A receiving normal saline; B: 40 mg/kg. bw CdCl2 + high‑fat
diet (HFD) + Suc; C: 40 mg/kg. bw BPA + HFD + Suc; D: 40 mg/kg. bw BPA + 40 mg/kg. bw
CdCl2 + HFD + Suc; and E: HFD + Suc orally for 56 days. Finally, brains were excised from each
group and the medial prefrontal cortex was dissected from both hemispheres with right hemisphere
samples processed for hematoxylin and eosin histology and left hemisphere samples homogenized
for biochemical evaluation of oxidative stress markers. One‑way analysis of variance and Tukey’s
post hoc test were used for data analysis with P < 0.05 considered statistically significant.
Results: From our findings, prefrontal glutathione levels were significantly lower (P < 0.05) in the
insulin‑resistant rats (Cd + BPA + HFD + Suc: 120.9 ± 21.89, HFD + Suc: 93.27 ± 17.29) compared
with control rats (244.0 ± 11.57), while prefrontal glutathione reductase activity was significantly
elevated (Cd + BPA + HFD + Suc: 41.02 ± 5.5, HFD + Suc: 41.09 ± 1.68, P < 0.05) compared
to the control rats (20.17 ± 3.27). Prefrontal neurons showed nuclear condensation, cytoplasmic
vacuolations, and clumping of cells. Conclusion: Morphological and biochemical evidence from
the present study suggests that environmental and metabolic factors do combine to induce profound
adverse effects on prefrontal microanatomy and antioxidant system.