Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh, India.
Biomed Pharmacother. 2019 Jan;109:351-359. doi: 10.1016/j.biopha.2018.10.070. Epub 2018 Nov 3.
This study examined the potency and efficacy of ascorbic acid (AA) in the management of depression-like behavior in diabetic rats. Diabetes mellitus was induced by single intraperitoneal injections of nicotinamide (120 mg/kg) and streptozotocin (65 mg/kg) administered 15 min apart. Diabetic (blood glucose ≥250 mg/dL) rats were subjected to intermittent foot-shocks to induce comorbid depression. Seven groups of diabetes comorbid depressed rats received vehicle (1 mL/kg) or AA (10, 25, 50, 100, 200, or 400 mg/kg) orally for eleven days. Three control groups namely- nondiabetic, diabetic, and depressed rats received the vehicles only. The potency (ED) and efficacy (E) of AA against immobility period, hypercorticosteronemia, adrenal hyperplasia, hyperglycemia, hypoinsulinemia, oxidative stress, and inflammatory response were estimated. AA administration caused a dose-dependent decrease (P < 0.05) in immobility period with maximum inhibition of 69% (efficacy) at 200 mg/kg and ED of 14 mg/kg (potency). AA at 200 mg/kg produced the maximal reduction in hypercorticosteronemia (55.1%) and adrenal hyperplasia (52.6%) with ED of 9.8 and 14.4 mg/kg, respectively. AA at 400 mg/kg produced the maximal reduction in hyperglycemia (35.5%), hypoinsulinemia (32.7%), and lipid peroxidation (82%) with ED of 18.6, 13.7, and 20.7 mg/kg, respectively. Moreover, AA at 400 mg/kg produced the maximal increase in SOD content (83%), CAT activity (77.9%), and IL-10 level (63%) with ED of 21.5, 21, and 21 mg/kg, respectively. In conclusion, the present results suggest that AA has therapeutic potential against diabetes comorbid depression but better regulation of hyperglycemia and hypoinsulinemia is required to achieve maximal benefits.
这项研究旨在探讨抗坏血酸（AA）在管理糖尿病大鼠抑郁样行为中的效力和疗效。糖尿病通过单次腹腔注射烟酰胺（120mg/kg）和链脲佐菌素（65mg/kg），间隔 15 分钟给药诱导。糖尿病（血糖≥250mg/dL）大鼠接受间歇性足底电击以诱导共病性抑郁。七组糖尿病共病性抑郁大鼠分别给予载体（1mL/kg）或 AA（10、25、50、100、200 或 400mg/kg）口服 11 天。三组对照，即非糖尿病、糖尿病和抑郁大鼠仅给予载体。评估 AA 对不动期、高皮质酮血症、肾上腺增生、高血糖、胰岛素血症、氧化应激和炎症反应的效力（ED）和疗效（E）。AA 给药呈剂量依赖性降低（P<0.05），最大抑制率为 69%（疗效），200mg/kg，ED 为 14mg/kg（效力）。AA 200mg/kg 可最大程度降低高皮质酮血症（55.1%）和肾上腺增生（52.6%），ED 分别为 9.8 和 14.4mg/kg。AA 400mg/kg 可最大程度降低高血糖（35.5%）、胰岛素血症（32.7%）和脂质过氧化（82%），ED 分别为 18.6、13.7 和 20.7mg/kg。此外，AA 400mg/kg 可最大程度增加 SOD 含量（83%）、CAT 活性（77.9%）和 IL-10 水平（63%），ED 分别为 21.5、21 和 21mg/kg。总之，本研究结果表明，AA 具有治疗糖尿病共病性抑郁的潜力，但需要更好地调节高血糖和胰岛素血症以达到最大获益。
