Protective Effect of Mirtazapine on Brain Tissue in Bleomycin-induced Neurotoxicity in Rats Model

Abstract

Neurotoxicity refers to the detrimental impact of chemical or biological agents on the structure and
function of the nervous system. It can result from various interrelated mechanisms, including oxidative stress,
neuroinflammation, mitochondrial dysfunction, and neuronal apoptosis. Bleomycin (BLM), a commonly used
chemotherapeutic agent, has been associated with neurotoxic effects, potentially mediated by oxidative damage
and mitochondrial impairment. However, the neuroprotective potential of mirtazapine against BLM-induced
neurotoxicity in central nervous system tissues remains inadequately explored. Aim: This study aimed to investigate
the protective effects of mirtazapine on brain tissue in a rat model of BLM-induced neurotoxicity, with a particular
focus on histopathological alterations. Methods: Thirty-five adult male Wistar rats were randomly assigned to
five groups: Control, BLM, BLM plus mirtazapine (15 or 30 mg/kg), and mirtazapine-only groups. Neurotoxicity
was induced through a single intratracheal dose of BLM (5 mg/kg), followed by daily oral administration of
mirtazapine for 14 days. On day 15, animals were euthanized, and brain tissues were harvested for histological
examination. Results: Histological assessment revealed that BLM caused significant neuronal degeneration in
the cerebral cortex and hippocampus. Mirtazapine at 15 mg/kg provided moderate neuroprotection, while the
30 mg/kg dose markedly preserved cortical and hippocampal architecture, indicating substantial histological
improvement. Conclusion: Mirtazapine exhibited a dose-dependent neuroprotective effect against BLM-induced
brain toxicity, likely through the preservation of neuronal integrity. These findings highlight its potential as a
therapeutic candidate for mitigating chemotherapy-related neurotoxicity.