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Crocin mediated amelioration of oxidative burden and inflammatory cascade suppresses diabetic nephropathy progression in diabetic rats
Chemico-Biological Interactions ( IF 4.7 ) Pub Date : 2018-02-03 , DOI: 10.1016/j.cbi.2018.02.001
Hadeer O. Abou-Hany , Hoda Atef , Eman Said , Hassan A. Elkashef , Hatem A. Salem

Diabetic Nephropathy (DN) is one of the main complications associated with diabetes mellitus. Persistently elevated blood glucose level drives histopathological changes in renal tissues that hinder normal kidney functions. In the current study, crocin; the main bioactive constituent of Crocus sativus was investigated as a reno-protective agent against DN by virtue of its numerous pharmacological activities. Diabetes was induced in male Sprague-Dawely rats through intravenous injection of streptozocin (STZ) (50 mg/kg), DN was confirmed eight weeks post diabetes induction. Daily oral crocin for eight weeks (20 mg/kg) significantly reduced blood glucose level with a significant increase in insulin level. Moreover, crocin improved impaired kidney functions as manifested in reduction of serum creatinine levels, blood urea nitrogen and proteinuria with concomitant increase in urinary creatinine clearance. Furthermore, biomarkers of cell injury and tissue necrosis like LDH activity was significantly reduced, kidney content of NOS significantly declined likewise. In addition, renal antioxidants such as SOD, GSH and serum catalase activity significantly increased with concomitant reduction of kidney MDA; biomarker of oxidative load. Kidney content of toll-like receptors 4 and IL-6 significantly declined with simultaneous suppression of nuclear factor kappa-B (NF-κB/p65) protein expression and immuno-staining in rat renal cortex. Furthermore, crocin inhibited progression of renal fibrosis as seen with reduction of renal hydroxyproline and collagen content, TGF-β immuno-staining and Masson's Trichrome positive tissue. Histopathologically, crocin pretreatment was associated with minimal renal damage with fewer fibrotic lesions. There was a concomitant restoration of renal tubules integrity with preservation of glomerular space area. In conclusion, crocin's ameliorative impact on DN may be attributed to its free radicals scavenging properties, its ability to enhance host antioxidant defense system and its ability to inhibit inflammatory and fibrotic cascades activation.



中文翻译:

番红花介导的氧化负荷和炎症级联的改善抑制了糖尿病大鼠的糖尿病肾病进展

糖尿病肾病(DN)是与糖尿病相关的主要并发症之一。持续升高的血糖水平会驱动肾脏组织的组织病理学改变,从而妨碍正常的肾功能。在当前的研究中,番红花;番红花的主要生物活性成分由于其众多的药理活性,其作为抗DN的肾保护剂被研究。通过静脉内注射链脲佐星(STZ)(50 mg / kg)在雄性Sprague-Dawely大鼠中诱发糖尿病,在诱发糖尿病八周后确认DN。每天口服番红花八周(20 mg / kg)可显着降低血糖水平,并显着增加胰岛素水平。此外,番红花改善了肾功能受损,表现为血清肌酐水平降低,血液尿素氮和蛋白尿减少,同时尿肌酐清除率增加。此外,细胞损伤和组织坏死的生物标志物(如LDH活性)显着降低,NOS的肾脏含量也显着下降。此外,肾脏抗氧化剂如SOD,随着肾脏MDA的降低,谷胱甘肽和血清过氧化氢酶活性显着增加。氧化负荷的生物标志物。在抑制大鼠肾皮质中核因子κB(NF-κB/ p65)蛋白表达和免疫染色的同时,toll​​样受体4和IL-6的肾脏含量显着下降。此外,如降低肾脏中的羟脯氨酸和胶原蛋白含量,TGF-β免疫染色和Masson's Trichrome阳性组织减少,番红花抑制了肾纤维化的进展。组织病理学上,番红花预处理与最小的肾脏损害和较少的纤维化病变有关。伴有肾小管完整性的恢复和肾小球间隙区域的保留。总之,番红花对DN的改善作用可能归因于其清除自由基的特性,

更新日期:2018-02-03
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