Carboxymethyl chitosan oligosaccharide prevents the progression of chronic kidney disease as a Nrf2-dependent apoptosis inhibitor

• CMCOS is safe and effective for the treatment of chronic kidney disease. • CMCOS is an apoptosis inhibitor for renal parenchymal cells. • The anti-apoptotic activity of CMCOS is based on its antioxidant regulation. • The anti-apoptotic effect of CMCOS rely on the activation of Nrf2 pathway. Chronic Kidney Disease (CKD) has become a global public health problem, for which satisfactory treatments remain an urgent need. Carboxymethyl chitosan oligosaccharide (CMCOS) is a small molecule derivative of the natural product chitin, which is easy to absorb with variety of biological activities. Our previous research has demonstrated the renal protective effects of CMCOS, while the underlying mechanism is poorly understood. This study reports that the renal protective effects of CMCOS are associated with anti-apoptosis in glomerular podocytes and renal tubular epithelial cells, which maintains the integrity of renal structure and function. Furthermore, CMCOS suppresses tissue oxidative stress and intracellular accumulation of reactive oxygen species both in vitro and in vivo, demonstrating positive correlations with its apoptosis inhibition. Mechanistically, CMCOS enhances endogenous antioxidant defense and relieves oxidative stress in the renal microenvironment through activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Specific inhibition of Nrf2 abolishes the apoptosis-inhibitory effect of CMCOS, indicating a dependence on this pathway. In conclusion, CMCOS activates Nrf2/HO-1 signaling pathway to inhibited oxidative stress-related apoptosis in renal parenchymal cells, thereby alleviating the progression of CKD. Our findings provide a new basis for the medicinal development of carbohydrates.