Acute kidney injury (AKI) most commonly appears in critically ill patients in hospitals. AKI is characterized as a quick deterioration of kidney function and has recently been identified to be tightly interlinked with chronic kidney diseases. The emerging major mediators of AKI include oxidative stress and endoplasmic reticulum (ER) stress. Carbon monoxide (CO) attenuates oxidative stress and ER stress in various cells, while Fyn, a member of the Src kinase family, is activated by oxidative stress and contributes to ER stress in skeletal muscle. Considering these, the objective of the current research was to determine (i) the involvement of Fyn in ER stress-mediated AKI and (ii) the effect of CO-releasing molecule-2 (CORM2) on reactive oxygen species- (ROS-) Fyn-ER stress-mediated AKI. Pretreatment with CORM2 (30 mg/kg) efficiently inhibited LPS (30 mg/kg)-induced oxidative stress, inflammation, and cellular apoptosis during AKI in C57BL/6J mice. Also, CORM2 efficiently suppressed the activation of Fyn and ER stress in AKI mice. Consistently, pretreatment with CORM2 inhibited oxidative stress, Fyn activation, ER stress, inflammation, and apoptosis in LPS- or H2O2-stimulated proximal epithelial tubular cells. Fyn inhibition using siRNA or an inhibitor (PP2) significantly attenuated ER stress responses in the cells. These data suggest that CORM2 may become a potential treatment option against ROS-Fyn-ER stress-mediated AKI.

Hypercholesterolemia, characterized by an increase in plasma low‐density lipoprotein (LDL) cholesterol and total cholesterol (TC), is the leading cause of non‐alcoholic fatty liver disease (NAFLD). The present study examined the effect of Heukcha extract (HCE), a naturally post‐fermented green tea extract, on diet‐induced hypercholesterolemia and related NAFLD in hamsters that metabolize lipids in a similar fashion to humans. The 10‐week‐old golden Syrian hamsters were fed a normal diet (ND) or a high cholesterol diet (HCD) containing 0.2% cholesterol and 10% lard, and some were also given HCE (200 or 500 mg/kg/day) orally for 12 weeks. The HCE did not affect the body weight gain, food intake, or the calorie intake. HCD significantly (p < 0.05) increased LDL (0.9 to 2.1 mmol/L), TC (2.7 to 7.8 mmol/L), and triglyceride (TG; 2.3 to 4.0 mmol/L), which was significantly decreased by 27.7%, 17.3%, and 60%, respectively, by HCE. HDL was significantly increased by HCD (0.6 to 1.6 mmol/L), but it was not affected by HCE administration. Furthermore, HCE suppressed HCD‐induced liver oxidative stress, fibrosis, and lipid accumulation almost to control levels. Interestingly, HCE significantly increased the protein level of cholesterol 7 alpha‐hydroxylase (CYP7A1), the rate‐limiting enzyme for bile acid synthesis, by 1.5‐fold in the liver. The present data suggest that HCE could be a functional food ingredient that can suppress the occurrence of diet‐induced hypercholesterolemia and NAFLD, possibly by increasing the expression of CYP7A1.

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