Akt inhibitor deguelin aggravates inflammation and fibrosis in myocarditis

نویسندگان

  • Bo Zhu Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts 02118, USA
  • Cheng qian Yin Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts 02118, USA
  • Chunming Zhao Human anatomy and Histology and Embryology, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China
  • Hongxing Cai Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China
  • Jiao Huang Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China
  • Meixiang Zhang Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China
  • Shanshan Li Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China
  • Wei Wang Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China
  • Xiaowei Yu Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China
  • Yue Wang Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China
  • Zhao Wang Department of Forensic Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China
چکیده مقاله:

Objective(s): Myocarditis is characterized by inflammatory cell infiltration in myocardial stroma. Attenuation of tumor necrosis factor (TNF)-α and interleukin (IL)-1β is a reliable mark for improving the prognosis. Protein kinase B (Akt) plays an important role in the development and progression of myocarditis. The specific role of the natural inhibitor of Akt, Deguelin, on myocarditis has not been reported. In this study, we used deguelin to investigate the effects of natural Akt inhibitor on myocarditis in experimental autoimmune myocarditis (EAM) rats.Materials and Methods: EAM rat models were made by using Lewis rats and Deguelin was injected intraperitoneally on day 3, 6, 9, 12 and 15 after successful modeling. On day 18, rats were sacrificed and the heart weight (HW)/ body weight (BW) ratio were measured. The pathological changes, pathological scores and fibrosis area were evaluated after H.&E.; and Masson’s trichrome staining. The mRNA levels of TNF-α and IL-1β were measured by RT-qPCR, while the protein expressions of TNF-α and IL-1β were detected by immunohistochemical staining and Western bolt. The protein expressions of Akt, Akt1, phosphorylated (p-) Akt and nuclear factor (NF)-κB were detected by Western bolt.Results: We found that the TNF-α and IL-1β levels, inflammatory scores and fibrosis areas were markedly increased after 18 days deguelin administration. Conclusion: Akt inhibition with deguelin may aggravate myocarditis of EAM rats.

برای دانلود باید عضویت طلایی داشته باشید

برای دسترسی به متن کامل این مقاله و 31 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

A DPP-4 Inhibitor Suppresses Fibrosis and Inflammation on Experimental Autoimmune Myocarditis in Mice

Myocarditis is a critical inflammatory disorder which causes life-threatening conditions. No specific or effective treatment has been established. DPP-4 inhibitors have salutary effects not only on type 2 diabetes but also on certain cardiovascular diseases. However, the role of a DPP-4 inhibitor on myocarditis has not been investigated. To clarify the effects of a DPP-4 inhibitor on myocarditi...

متن کامل

CX3CR1 knockout aggravates Coxsackievirus B3-induced myocarditis

Studies on inflammatory disorders elucidated the pivotal role of the CX3CL1/CX3CR1 axis with respect to the pathophysiology and diseases progression. Coxsackievirus B3 (CVB3)-induced myocarditis is associated with severe cardiac inflammation, which may progress to heart failure. We therefore investigated the influence of CX3CR1 ablation in the model of acute myocarditis, which was induced by in...

متن کامل

Chemopreventive effects of deguelin, a novel Akt inhibitor, on tobacco-induced lung tumorigenesis.

Tobacco carcinogens induce Akt activation and lung carcinogenesis. We previously demonstrated that deguelin, a natural plant product, specifically inhibits the proliferation of premalignant and malignant human bronchial epithelial cells by blocking Akt activation. To evaluate the ability of deguelin to block tobacco carcinogen-induced lung tumorigenesis, we evaluated the in vivo effects of degu...

متن کامل

Estrogen aggravates inflammation in Pseudomonas aeruginosa pneumonia in cystic fibrosis mice

BACKGROUND Among patients with cystic fibrosis (CF), females have worse pulmonary function and survival than males, primarily due to chronic lung inflammation and infection with Pseudomonas aeruginosa (P. aeruginosa). A role for gender hormones in the causation of the CF "gender gap" has been proposed. The female gender hormone 17β-estradiol (E2) plays a complex immunomodulatory role in humans ...

متن کامل

Changes in Glycosylation of Alpha-1-Protease Inhibitor in Inflammation (Rheumatoid Arthritis and Crohn\'s Disease)

Alpha-1-proteinase inhibitor (API) is one of the acute phase proteins. Following an inflammatory stimuli the concentration of API increased up to four folds. Accompanying these quantitative changes, there is qualitative alterations in the structure of carbohydrate moiety (glycosylation). To determine the alterations in the glycosylation of API in inflammation, API was isolated from the sera of...

متن کامل

S100A9 aggravates bleomycin-induced dermal fibrosis in mice via activation of ERK1/2 MAPK and NF-κB pathways

Objective(s): This study aims to investigate the pathogenicity and possible mechanisms of S100A9 function in mice models of scleroderma. Materials and Methods: The content of S100A9 in the skin tissues of mice with scleroderma was determined. Different concentrations of bleomycin (BLM) and S100A9 were subcutaneously injected into the backs of mice simultaneously, and then pathological changes i...

متن کامل

ذخیره در منابع من

ذخیره در منابع من قبلا به منابع من ذحیره شده

{@ msg_add @}

  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید


عنوان ژورنال

دوره 22  شماره 11

صفحات  1275- 1282

تاریخ انتشار 2019-11-01

با دنبال کردن یک ژورنال هنگامی که شماره جدید این ژورنال منتشر می شود به شما از طریق ایمیل اطلاع داده می شود.

کلمات کلیدی

میزبانی شده توسط پلتفرم ابری doprax.com

copyright © 2015-2023