Pachymic acid ameliorates sepsis-induced acute kidney injury by suppressing inflammation and activating the Nrf2/HO-1 pathway in rats

Z.-Y. Cai, Z.-X. Sheng, H. Yao

Department of Renal Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China. baobei000536@qq.com

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• Pharmacology

OBJECTIVE: To investigate the protective effects and underlying mechanisms of pachymic acid (PA) on sepsis-induced acute kidney injury (AKI).

MATERIALS AND METHODS: Sepsis-induced AKI model was made by cecal ligation and puncture (CLP) surgery in SD rats. Animals were randomly divided into 5 groups: a sham group, a CLP group, and three PA-treated groups, which received intraperitoneal injection of PA at the dosage of 5, 20 and 50 mg/kg.bw, respectively. Kidney index, Cre and BUN contents were determined to evaluate the renal function. Pathological changes of kidney tissue were observed by HE staining. Levels of inflammatory mediators (TNF-α, IL-6) were measured to assess the inflammation in renal tissue. Moreover, the expression levels of iNOS, Nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were studied by Real-time PCR and Western blot.

RESULTS: PA treatment can significantly decrease the kidney index, and notably drop the contents of Cre and BUN. Renal pathological damage was also found to be effectively improved by PA in a dose-dependent manner. PA treatment was observed to inhibit the renal inflammation by reducing the TNF-α and IL-6 levels. Besides, PA treatment significantly decreased the expression levels of iNOS, and enhanced the expression of Nrf2 and HO-1 in the kidney.

CONCLUSIONS: PA had potential therapeutic effects on sepsis-induced AKI in rats, and the activity may be associated with the anti-inflammatory function and antioxidant effect via activating Nrf2/ HO-1 pathway.

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