Background: Benzodiazepines (BZDs) are a class of depressant drugs that have enjoyed widespread use
in conventional clinical management of anxiety-related conditions such as panic disorders that require
therapeutic central relaxation and sedation. Meanwhile, prolonged administration of benzodiazepines even
at low doses has however been linked to variety of undesirable effects such as discontinuation relapse with
the associated risk of abuse and dependency. Aim: This study investigated the behavioral, histological
and biochemical outcomes of long-term low dose diazepam use and explored the potential role of nigella
sativa oil (NSO) in the amelioration of the associated side effects. Methods: Adult Wistar rats (n=32)
were randomized into four groups that received normal saline; diazepam; diazepam + NSO; or NSO only,
respectively for 14 days. At the end of the period of the various exposures, the rats were taken through
behavioral paradigms after which they were sacrificed for chemical and histological profiling. Results:
diazepam-exposed rats exhibited stress-related manifestations with relatively poor performance in memory-
related tasks. Repeated diazepam ingestion reduced brain antioxidant biomarkers while causing elevation
of brain oxidative stress markers. On histological observation, mild degenerative changes were evident
in the various brain regions of the diazepam-exposed rats. Conclusion: Interventional nigella sativa oil
administration showed therapeutic potentials by mitigating and reversing the observed effects of diazepam,
largely due to its antioxidant and anti-inflammatory effects as observed in the present study.

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.