ABSTRACT
Selenium nanoparticles (SeNPs) are well reported to exhibit pharmacological activities both in vitro and in vivo. However, literature is devoid of studies on the impact of SeNPs and/or metformin (M) against streptozotocin (STZ)-mediated oxidative brain injury and behavioral impairment. Consequently, to fill this gap, diabetes was induced in male Wistar rats by feeding with 10% fructose solution for 2 weeks, followed by a single dose intraperitoneal injection of STZ (40 mg/kg body weight [bwt]). After rats were confirmed diabetic, they were treated orally with 0.1 mg/kg bwt of SeNPs ± M (50 mg/kg bwt), and normal control (NC) received citrate buffer (2 mg/mL) for 5 weeks. In comparison with the diabetic control (DC), SeNPs, and/or M significantly (p < 0.05) lowered blood glucose levels, but increased insulin secretion and pancreatic ß-cell function. An increase in locomotor and motor activities evidenced by improved spontaneous alternation, locomotor frequency, hinding, and increased mobility time were observed in treated groups. In addition, there was enhanced brain antioxidant status with a lower acetylcholinesterase (AChE) activity and oxidative-inflammatory stress biomarkers. A significant downregulation of caspase 3 and upregulation of parvalbumin and Nrf2 protein expressions was observed in treated groups. In some of the studied parameters, treated groups were statistically (p < 0.05) insignificant compared with the normal control (NC) group. Overall, co-treatment elicited more efficacy than that of the individual regimen.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Metformin/administration & dosage , Nanoparticles/administration & dosage , Selenium/administration & dosage , Acetylcholinesterase/metabolism , Animals , Behavior, Animal/drug effects , Brain/drug effects , Brain/metabolism , Caspase 3/metabolism , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/metabolism , Drug Therapy, Combination , Glutathione/metabolism , Glutathione Transferase/metabolism , Insulin/blood , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Male , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Oxidoreductases/metabolism , Parvalbumins/metabolism , Rats, WistarABSTRACT
OBJECTIVES: Loranthus micranthus is widely used in Nigerian folklore treatment of male infertility and diabetes complications. We investigated this claim in rats rendered diabetic by streptozotocin (STZ). METHODS: Induction of diabetes mellitus in adult male Wistar rats was by intraperitoneal injection of STZ (60 mg/kg). The diabetic rats were thereafter treated orally once/day with 5 mg/kg Gilbenclamide or L. micranthus (100 mg/kg or 200 mg/kg) and monitored for 14 days. Clinical observations, hormonal profile, oxidative stress parameters, glucose metabolism enzymes, histopathological examination, apoptotic marker immunoreactivity and western blotting in testes and sperm parameters were evaluated to examine effects of L. micranthus on STZ-diabetic rats. RESULTS: L. micranthus treatment significantly reduced the blood glucose level (45.9% and 84.7% on the 7th and 14th post-treatment days, respectively); increased antioxidant status, improved microarchitecture of testes, reduced lipid peroxidation and increased BCl-2 protein expression in diabetic rats relative to control. Furthermore, treatment with L. micranthus increased steroidogenic enzymes activities, levels of steroid hormones and improved sperm quality, relative to control. CONCLUSION: The anti-diabetic and aphrodisiac properties exhibited by L. micranthus could be contingent on its ability to restore a balance to the compromised redox status that characterizes male reproductive dysfunction in diabetes.
