Crocin protects against endoplasmic reticulum stress-related tubular injury in diabetic nephropathy via the activation of the PI۳K/AKT/Nrf۲ pathway

Objective(s): Diabetic nephropathy (DN) is the main cause of end-stage renal disease, but the current treatment is not satisfactory. Crocin is a major bioactive compound of saffron with antioxidant and anti-endoplasmic reticulum stress (ERS) abilities used to treat diabetes. This study specifically investigated whether crocin has a regulatory role in renal injury in DN.Materials and Methods: The experiment was divided into control, (db/m mice), model (db/db mice), and experimental groups (db/db mice were intraperitoneally injected with ۴۰ mg/kg crocin). Renal function-related indicators (Scr, BUN, FBG, UP, TG, TC, ALT, and AST) and oxidative stress-related indicators (ROS, MDA, GSH, SOD, and CAT) were assessed. The pathological changes of renal tissues were confirmed by HE, Masson, PAS, and TUNEL staining. The levels of ERS-related proteins (GRP۷۸ and CHOP), apoptosis-related proteins, and PI۳K/AKT and Nrf۲ pathways-related proteins in renal tissue were detected. Results: In db/db mice, renal function-related indicators, apoptotic cells of renal tissues, the contents of ROS and MDA as well as the expressions of CHOP, GRP۷۸, and Bax were increased, the degree of renal tissue damage was aggravated, while the contents of GSH, SOD, and CAT, as well as the protein levels of Nrf۲, PARP, anti-apoptotic proteins (Mcl-۱, Bcl-۲, Bcl-xl) were decreased compared to the db/m mice. However, crocin treatment reversed the above-mentioned situation. The expressions of the PI۳K/AKT and Nrf۲ pathways-related proteins were also activated by crocin.Conclusion: Crocin inhibited oxidative stress and ERS-induced kidney injury in db/db mice by activating the PI۳K/AKT and Nrf۲ pathways.

Keywords:

Crocin , Diabetic nephropathy , Endoplasmic reticulum - stress , Kidney Injury , PI۳K/Akt