Aqueous Extract of Cola nitida and Garcinia kola Synergistically Enhances Hippocampal-hypothalamic Glutamate and Na+ /K+ -ATPase Activity in Male Wistar Rats.

BACKGROUND: The incidence of cognitive decline has been proposed to rise exponentially in the coming years. Therapies targeting molecular pathways involved in the enhancement of memory and energy regulation could be a major breakthrough in the prevention or management of dementia in susceptible populations. OBJECTIVES: This study investigated the effects of aqueous extracts of Cola nitida (AECONS) and Garcinia kola (AEGAK) on glutamate level and Na+/K+-ATPase activity in the hippocampus and hypothalamus of male Wistar rats. METHODS: Adult male Wistar rats (170-200) were randomly allotted into groups (n=5/group); control (distilled water p.o.), AECONS1 (200 mg/kg), AECONS2 (400 mg/kg), AEGAK1 (200 mg/kg), AEGAK2 (400 mg/kg), AECONS1+AEGAK1 and AECONS2+AEGAK2. The extract was prepared and the administration was done daily for 6 weeks. RESULTS AND DISCUSSION: Administration of AECONS or AEGAK increased plasma, hippocampal and hypothalamic glutamate, Na+/K+-ATPase activity, NO, SOD except hippocampal glutamate in AECONS1/AEGAK1, Na+/K+-ATPase activity and SOD in AEGAK1, hypothalamic glutamate and SOD in AECONS1 when compared with control. Besides, MDA level decreased in AEGAK2 and hippocampal but not hypothalamic MDA decreased in AEGAK1 compared with control. However, concomitant administration of AECONS and AEGAK enhanced plasma, hippocampal and hypothalamic biomarkers except hypothalamic MDA level. The present study demonstrates that AECONS and AEGAK synergistically enhance hippocampal and hypothalamic glutamate and Na+/K+- ATPase activity, which are accompanied by NO and SOD-dependent antioxidant enrichment. CONCLUSION: These findings, therefore, suggest that AECONS+AEGAK could be a better therapeutic candidate in hippocampal-hypothalamic-related neurodegenerative diseases.

Acetate ameliorates nephrotoxicity in streptozotocin-nicotinamide-induced diabetic rats: Involvement of xanthine oxidase activity.

Impaired renal function is a common complication of diabetes mellitus (DM) that often degenerates to cardiovascular disease, contributing to high morbidity and reduced survival worldwide. Short chain fatty acids (SCFAs), including acetate has shown potential benefits in glycemic or metabolic regulation but its effect on diabetes-associated renal toxicity/impairment is not clear. Herein, we investigated the hypothesis that acetate would ameliorate renal toxicity, accompanying DM, possibly by suppression of xanthine oxidase (XO) activity. Adult male Wistar rats (230-260 g) were allotted into groups (n = 6/group) namely: control (vehicle; po), sodium acetate (NaAc)-treated (200 mg/kg), diabetic with or without NaAc groups. DM was induced by intraperitoneal injection of streptozotocin 65 mg/kg after a dose of nicotinamide (110 mg/kg). Diabetic animals showed increased fasting glucose and insulin, renal triglyceride, total cholesterol, atherogenic lipid, malondialdehyde, XO, tissue necrosis factor-α, uric acid, interleukin-6, aspartate transaminase/alanine aminotransferase ratio, gamma-glutamyl transferase and decreased glutathione and nitric oxide concentration. The renal tissue was characterized with disrupted tissue architecture, enlarged Bowman's space, congested glomeruli and adherence of abnormal segments of tuft to Bowman's capsule with consequent elevated serum creatinine and urea concentration. However, these alterations were attenuated by NaAc. The study demonstrates that acetate ameliorates diabetes-induced nephrotoxicity, which is associated with suppressed XO and its accompanied pro-inflammatory mediators. Therefore, SCFAs, acetate would be a promising dietary-derived therapeutic agent for the prevention and management of diabetes-associated renal disturbances.

Protective role of glutamine against cadmium-induced testicular dysfunction in Wistar rats: Involvement of G6PD activity.

BACKGROUND: Endocrine disruptor such as cadmium has been widely reported to cause testicular toxicity, which contributes to recent decline in male fertility worldwide. Glutamine, the most abundant amino acid in the body has been demonstrated to exert protective effects in cellular toxicity. However, its role in testicular toxicity is unknown. The present study is therefore aimed at investigating the effects of glutamine supplementation on cadmium-induced testicular toxicity, and the possible involvement of glucose-6-phosphate dehydrogenase (G6PD) activity. MATERIALS AND METHOD: Male Wistar rats weighing 160-190 g were allotted into 4 groups (n = 5/group): The groups received vehicle (distilled water; p.o.), glutamine (1gkg-1; p.o.), cadmium chloride (5mgkg-1p.o.) and Cadmium chloride plus glutamine respectively, daily for 30 days. Biochemical and histological analyses were performed with appropriate method. RESULTS: Administration of cadmium significantly decreased body weight, sperm count, motility and viability, as well as altered sperm morphology and progressivity. Cadmium also caused atrophy of the seminiferous tubule in addition to disrupted testicular architecture, lumen, Sertoli cells and spermatogonia. Similarly, serum and testicular aspartate transaminase, and malondialdehyde significantly increased, and G6PD, glutathione, nicotinamide adenine dinucleotide phosphate and nitric oxide significantly decreased with corresponding decrease in follicle stimulating hormone, luteinizing hormone and testosterone in cadmium-treated animals compared with control groups. However, supplementation with glutamine attenuated these alterations. CONCLUSION: The present study demonstrates that cadmium induces testicular dysfunction that is attributable to defective G6PD and accompanied by increased lipid peroxidation and impaired NO-dependent endothelial function. Interestingly, glutamine supplementation ameliorates cadmium-induced testicular dysfunction through enhancement of G6PD activity.