Celastrol aggravates LPS-induced inflammation and injuries of liver and kidney in mice

American Journal of Translational Research

Mengqiu Wu¹  Weiyi Chen²  Xiaowen Yu³ 

[1] Department of Nephrology, Childrens Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing 210008, P. R. of China;Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing 210029, China;Nanjing Key Laboratory of Pediatrics, Childrens Hospital of Nanjing Medical University, Nanjing 210008, China

关键词: LPS;    celastrol;    inflammation;    liver injury;    kidney injury;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Sepsis, a life-threatening syndrome with uncontrolled inflammatory response, causes high morbidity and mortality worldwide. Currently, satisfactory treatments on sepsis are still lacking in clinic. Thus, new therapeutic strategies are urgently required. Recently, celastrol, a pentacyclic triterpene extracted from the traditional Chinese medicine Tripterygium Wilfordi plant, attracted great interest for its properties of anti-inflammation, anti-oxidative stress, and metabolism remodeling. However, the effect of celastrol on sepsis is still unclear. In this study, we investigated the effect of celastrol on lipopolysaccharides (LPS)-induced inflammation and organ injuries in mice. Following celastrol pretreatment, mice showed increased mortality rate and aggravated inflammation evidenced by further enhanced inflammatory markers of IL-6, IL-1β, TNF-α, IL-18, MCP-1, and ICAM-1 in circulation, liver, and kidney after LPS treatment. The serum levels of ALT, AST, and LDH were further increased in parallel with the deteriorated liver morphological damage (H&E) and oxidative stress in celastrol-treated mice, indicating an aggravated liver injury. In kidney, the expressions of tubular injury markers of kidney injury molecule-1 (KIM-1) and gelatinase-associated lipocalin (NGAL) were further upregulated along with higher levels of blood urea nitrogen (BUN), creatinine (Cr), and MDA in celastrol-treated mice. These findings not only indicated a detrimental role of celastrol therapy in LPS-induced inflammation and organ injuries but also suggested the restriction of celastrol usage in sepsis patients.

【 授权许可】

CC BY-NC