Kolaviron abates busulfan-induced episodic memory deficit and testicular dysfunction in rats: The implications for neuroendopathobiological changes during chemotherapy

Busulfan is a popular antileukemia chemotherapeutic alkylating agent widely known to induce variety of serious adverse effects including chemobrain-related cognitive impairments and dysfunction in male reproductive system. Whether kolaviron, a neuro- and repro-active compound obtained from Garcinia kola, with neuroprotective and reproductive-promoting activities, mitigates busulfan-induced cognitive and male reproductive impairments remain unknown. Hence, we investigated the reversal effects of kolaviron on busulfan-induced episodic memory deficit and testicular dysfunction, and its underlying mechanisms in male rats. In the treatment-protocol, rats in groups 1 and 2 received saline (10 mL/kg/p.o./day) and DMSO (10 mL/kg/p.o./day) respectively, group 3 was given kolaviron (200 mg/kg/p.o./day), group 4 received busulfan (50 mg/kg/p.o./day) and group 5 was pretreated with busulfan (50 mg/kg/p.o./day) consecutively for 56 days prior to kolaviron treatment (200 mg/kg/p.o./day) from days 29-56. Episodic memory deficit was assessed using passive avoidance task (PAT). Following euthanization, blood samples, epididymal sperm, testes and brain were harvested and hormonal and neurochemical contents and their metabolizing enzymes were assayed. Kolaviron reversed busulfan-induced episodic cognitive deficit in the PAT. The reduced serotonin, dopamine, noradrenaline concentrations, elevated glutamate levels, acetylcholinesterase, monoamine oxidase-A and B activities were normalized by kolaviron. Kolaviron also reversed the busulfan-induced decreased testicular/body weights and spermatogenesis. Kolaviron abated busulfan-induced changes in androgenic hormones (testosterone, FSH, LH), dehydrogenase enzymes (3ß-HSD and 17ß-HSD), altered sperm-chromatin, sperm-membrane integrity and sperm-acrosomal reaction and capacitation impairments. Our findings suggest that kolaviron could mitigate busulfan-induced episodic memory deficit and dysfunction in male reproductive system via neurochemical modulations and increase testicular androgenic hormones/enzymes in rats.