Abstract
Diabetic nephropathy (DN) is by far the most common cause of end‑stage renal disease (ESRD) in industrial countries, accounting for ~45% of all new ESRD cases in the United States. Grape seed proanthocyanidin extracts (GSPE) are powerful antioxidants, with an antioxidant ability 50‑fold greater than that of vitamin E and 20‑fold greater than that of vitamin C. The present study investigated whether GSPE can protect against streptozotocin (STZ)‑induced DN and aimed to elucidate a possible mechanism. Male Sprague Dawley rats were randomly divided into three groups: Control group (N), diabetes mellitus group (DM) injected with 40 mg/kg STZ, and the GSPE treatment group (intragastric administration of 250 mg/kg/day GSPE for 16 weeks after diabetes was induced in the rats). Blood and kidney samples were collected after treatment. The renal pathological changes were determined with periodic acid‑Schiff (PAS) staining, while the protein expression levels of glucose‑regulated protein 78 (GRP78), phosphorylated‑extracellular signal‑regulated kinase (p‑ERK) and Caspase‑12 were determined by western blotting and immunohistochemical staining. Apoptosis was determined with a terminal deoxynucleotidyl transferase dUTP nick‑end labeling (TUNEL) assay. Compared with the DM group, the GSPE group had no significant changes in the blood urea nitrogen (BUN) level and serum creatinine (Scr) level, but showed a significant decline in the renal index (RI) level and 24‑h urinary albumin level (P<0.05). The histopathology results indicated very little pathological damage in the GSPE group. Compared with the DM group, the GSPE group had a significantly reduced number of TUNEL‑positive cells (P<0.05), and the GSPE group had an obvious reduction in the protein expression of GRP78, p‑ERK, and Caspase‑12 (P<0.05). In this study, the results indicated that GSPE can protect renal function and attenuate endoplasmic reticulum stress‑induced apoptosis via the Caspase‑12 pathway in STZ‑induced DN.