NEUROPROTECTIVE ROLE OF PHOSPHODIESTERASE-5 INHIBITOR IN CYCLOPHOSPHAMIDE-INDUCED COGNITIVE DEFICITS: BEHAVIORAL AND BIOCHEMICAL ASSESSMENT IN SWISS ALBINO MICE.

Abstract

Background: Chemotherapy-induced cognitive impairment, often referred to as "chemobrain," is a common and debilitating side effect of cancer treatment. Cyclophosphamide (CPA), a widely used chemotherapeutic agent, is known to induce oxidative stress and cognitive dysfunction. Phosphodiesterase-5 (PDE-5) inhibitors have shown neuroprotective potential by enhancing cGMP signaling, improving cerebral blood flow, and reducing oxidative damage. This study aimed to evaluate the neuroprotective effects of a PDE-5 inhibitor against CPA-induced cognitive deficits in Swiss albino mice.

Methods: Male Swiss albino mice (35–40 g) were divided into four groups (n = 6/group): Control, CPA (100 mg/kg, i.p., single dose), PDE-5 inhibitor only (5 mg/kg, p.o.), and CPA + PDE-5 inhibitor. The PDE-5 inhibitor was administered daily for 14 days. Cognitive function was assessed using the Y-maze and Novel Object Recognition (NOR) tests. Biochemical analyses of brain tissues included malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and acetylcholinesterase (AChE) activity.

Results: CPA administration significantly impaired spatial and recognition memory, increased MDA levels, and reduced GSH and SOD activity, along with elevated AChE activity. Treatment with the PDE-5 inhibitor significantly reversed these effects, improving behavioral performance and restoring oxidative and cholinergic balance.

Conclusion: PDE-5 inhibition demonstrated significant neuroprotective effects against CPA-induced cognitive dysfunction in mice, likely via antioxidant and cholinergic mechanisms. These findings support the potential therapeutic role of PDE-5 inhibitors in managing chemotherapy-related cognitive impairment.