Obafemi Tajudeen O, Jaiyesimi Kikelomo F, Olomola Adenike A, Olasehinde Oluwaseun R, Olaoye Oyindamola A, Adewumi Funmilayo D, Afolabi Blessing A, Adewale Olusola B, Akintayo Christopher O, Ojo Oluwafemi A
Department of Biochemistry, Afe Babalola University, PMB 5454, Ado-Ekiti, Nigeria.
Medical Biochemistry Unit, College of Health Sciences, Afe Babalola University, PMB 5454, Ado-Ekiti, Nigeria.
Toxicol Rep. 2021 Jul 17;8:1419-1427. doi: 10.1016/j.toxrep.2021.07.011. eCollection 2021.
Over time, diabetes patients usually need combination therapy involving two or more agents, including phytonutrients to attain therapeutic targets. The purpose of this research is to elucidate the combined effect of metformin and gallic acid (GA) on glucose metabolism, inflammation as well as oxidative and endoplasmic reticulum (ER) stresses in fructose-fed diabetic rats. Thirty-five rats of Wistar strain were arbitrarily distributed into five groups, each containing seven animals as follows: normal control, diabetic control, groups administered 100 mg/kg bw metformin only, 50 mg/kg bw gallic acid only and a combination of both. Experimental animals were made diabetic by single injection of 40 mg/kg streptozotocin (intraperitoneally) subsequent to 14 days administration of 10 % fructose prior. Treatment of rats continued for 21 days following diabetes confirmation. Glucose and insulin levels as well as lipid profile were evaluated in the serum, while activities of catalase and superoxide dismutase were estimated in both liver and pancreas. In addition, levels of malondialdehyde, interleukin-6 and tumor necrosis factor-alpha, as well as expression of activating transcription factor-4 were evaluated in liver and pancreas of diabetic rats. Activities of glucose-6-phosphatase and glucokinase were also determined in liver of diabetic animals. Metformin only, GA only and combination of metformin and GA significantly improved antioxidant status and glucose homeostasis while inflammation and endoplasmic reticulum stress were significantly ameliorated in diabetic rats. Metformin/GA combination appeared to improve glucose metabolism by increasing insulin level and ameliorating the dysregulated activities of glucose metabolizing enzymes and ER stress better than either metformin only or GA only. It could be concluded that coadministration of metformin/GA produced a combined effect in ameliorating diabetes in Wistar rats and could be considered in treatment of diabetes.
随着时间的推移，糖尿病患者通常需要联合使用两种或更多药物进行治疗，包括植物营养素以达到治疗目标。本研究的目的是阐明二甲双胍和没食子酸（GA）对喂食果糖的糖尿病大鼠的糖代谢、炎症以及氧化应激和内质网（ER）应激的联合作用。将35只Wistar品系大鼠随机分为五组，每组7只，分组如下：正常对照组、糖尿病对照组、仅给予100 mg/kg体重二甲双胍的组、仅给予50 mg/kg体重没食子酸的组以及两者联合使用的组。在预先给予10%果糖14天之后，通过单次腹腔注射40 mg/kg链脲佐菌素使实验动物患糖尿病。在确认糖尿病后，对大鼠的治疗持续21天。检测血清中的葡萄糖和胰岛素水平以及血脂谱，同时测定肝脏和胰腺中过氧化氢酶和超氧化物歧化酶的活性。此外，评估糖尿病大鼠肝脏和胰腺中丙二醛、白细胞介素-6和肿瘤坏死因子-α的水平以及激活转录因子-4的表达。还测定糖尿病动物肝脏中葡萄糖-6-磷酸酶和葡萄糖激酶的活性。仅二甲双胍组、仅GA组以及二甲双胍与GA联合使用组均显著改善了抗氧化状态和葡萄糖稳态，同时糖尿病大鼠的炎症和内质网应激得到显著改善。二甲双胍/GA联合使用似乎比仅使用二甲双胍或仅使用GA更能通过提高胰岛素水平以及改善糖代谢酶的失调活性和内质网应激来改善糖代谢。可以得出结论，二甲双胍/GA联合给药在改善Wistar大鼠糖尿病方面产生了联合作用，可考虑用于糖尿病治疗。
