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1,8-桉叶素通过诱导乙二醛酶-I的活性和降低转化生长因子-1β的水平,保护2型糖尿病大鼠免受糖尿病肾病的侵害。

1,8 cineole protects type 2 diabetic rats against diabetic nephropathy via inducing the activity of glyoxalase-I and lowering the level of transforming growth factor-1β.

作者信息

Mahdavifard Sina, Nakhjavani Manochehr

机构信息

Department of Clinical Biochemistry, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.

Endocrine Division, Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

J Diabetes Metab Disord. 2022 Mar 9;21(1):567-572. doi: 10.1007/s40200-022-01014-2. eCollection 2022 Jun.

Abstract

PURPOSE

Diabetes leading to the production and circulation of glycation products along with the reduction of the activity of glyoxalase-I (GLO-I) contribute to diabetic nephropathy. Therefore, we studied the effect of 1,8 cineole (Cin) on the formation of diverse glycation products and the activity of GLO-I as well as renal histopathological alterations in the type-2 diabetic rat.

METHODS

Type 2 diabetes was induced in rats with a combination of streptozotocin and nicotinamide (55 + 200 mg/kg). Two groups of rats, normal and diabetic, were treated intragastrically with Cin (200 mg/kg) once daily for 2 months. Fasting blood sugar, insulin resistance index, lipid profile, the activity of GLO-I, glycation products (Glycated albumin, Glycated LDL, Methylglyoxal, and advanced glycation end products), and oxidative stress (Advanced oxidation protein products, malondialdehyde, oxidized LDL, and reduced glutathione), inflammatory markers (Tumor necrosis factor-α and Transforming growth factor-1β), creatinine in the serum (Cre), and proteinuria (PU) in the urine of all rats was determined as well as renal histopathological alterations were investigated.

RESULTS

Cin reduced biochemical (Cre and PU) and histopathological (glomerulosclerosis) indicators of renal dysfunction in the diabetic rat compared to untreated diabetic rats. Moreover, the treatment decreased different glycation, oxidative stress, and pro-inflammatory markers  <  Further, Cin had an advantageous effect on glucose and lipid metabolism.

CONCLUSIONS

Cin ameliorated diabetic nephropathy via reduction of TGF-1β following to decrease the formation of different glycation products, oxidative stress, and inflammatory process with the induction of the activity of glyoxalase-I in type 2 diabetic rats.

摘要

目的

糖尿病导致糖基化产物的产生和循环,同时乙二醛酶 -I(GLO-I)活性降低,这些因素共同导致糖尿病肾病。因此,我们研究了1,8 -桉叶素(Cin)对2型糖尿病大鼠多种糖基化产物形成、GLO-I活性以及肾脏组织病理学改变的影响。

方法

采用链脲佐菌素和烟酰胺(55 + 200 mg/kg)联合诱导大鼠患2型糖尿病。将两组大鼠,即正常组和糖尿病组,每天经胃内给予Cin(200 mg/kg),持续2个月。测定所有大鼠的空腹血糖、胰岛素抵抗指数、血脂谱、GLO-I活性、糖基化产物(糖化白蛋白、糖化低密度脂蛋白、甲基乙二醛和晚期糖基化终产物)、氧化应激(晚期氧化蛋白产物、丙二醛、氧化低密度脂蛋白和还原型谷胱甘肽)、炎症标志物(肿瘤坏死因子-α和转化生长因子-1β)、血清肌酐(Cre)以及尿蛋白(PU),并研究肾脏组织病理学改变。

结果

与未治疗的糖尿病大鼠相比,Cin降低了糖尿病大鼠肾功能不全的生化指标(Cre和PU)和组织病理学指标(肾小球硬化)。此外,该治疗降低了不同的糖基化、氧化应激和促炎标志物。此外,Cin对葡萄糖和脂质代谢有有益影响。

结论

在2型糖尿病大鼠中,Cin通过降低转化生长因子-1β,进而减少不同糖基化产物的形成、氧化应激和炎症过程,并诱导乙二醛酶-I的活性,从而改善糖尿病肾病。

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