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.

Adansonia digitata L. leaf extract attenuates lead-induced cortical histoarchitectural changes and oxidative stress in the prefrontal cortex of adult male Wistar rats.

Objectives Adansonia digitata L. is popularly known for the management of various neurological diseases in ethno-medicine. Studies have shown that lead toxicity is a possible risk factor for early onset of neurodegenerative disease. Hence, this study was designed to evaluate the effect of A. digitata aqueous leaf extract (ADALE) against lead-induced oxidative stress and histo-architectural changes in the prefrontal cortex of adult Wistar rats. Methods Saline (10 mL/kg), ADALE (500 and 1000 mg/kg) and EDTA (55 mg/kg) were pretreated orally 30 min prior to lead acetate (LA) (120 mg/kg) administration to male Wistar rats (n=7) for 21 days. Thereafter, standard biochemical (superoxide dismutate, catalase, glutathionxe and malondialdehyde), histological (H&E) and histochemical assessment (crystyl fast violet stain for nissil substance) were carried out in the prefrontal cortex. Results ADALE significantly (p<0.05) reversed LA-induced oxidative stress, as evidenced by increased catalase, superoxide dismutase and oxidized glutathione levels, and decreased malondialdehyde concentration in the prefrontal cortex. Also, the increase chromatolysis and neuronal pyknosis of the pyramidal neurons of the prefrontal cortex were significantly attenuated by ADALE. Conclusions The result of this study showed that A. digitata aqueous leaf extract attenuated lead acetate-induced cortical neurodegeneration via inhibition of oxidative stress.