Investigation of the effects of boron on PAR1-mediated NLRP3 inflammasome in experimental diabetic nephropathy using molecular and pathological methods

Diabetic nephropathy (DN) is one of the microvascular complications of diabetes that impairs life and may result in end-stage renal failure. Increased inflammatory changes and inflammation in kidney tissue suggest that they are potential modulators of DN. This work; The role of diabetic nephropathy treatment and the anti-thrombotic, anti-inflammatory effects of boric acid on diabetic nephropathy are planned to be revealed. In the study, diabetes was induced with streptozotocin (50 mg/kg intraperitoneally) in Sprague Dawley rats, combined with boric acid (50, 100 and 200 mg/kg) by oral gavage for 63 days. Weekly body weight and fasting blood glucose levels were measured. At the end of the experiment, blood, pancreas and kidney tissue were taken because biochemical, strict and serological individuals were found. Kidney and pancreatic tissues were examined histopathologically (hematoxylin-eosin, periodic acid Schiff). In kidney tissue, immunohistochemistry (NLRP3, caspase-1, NF-κβ, PAR-1, ki67, VEGF), real-time qPCR (NLRP3 and PAR-1), Western Blot (NLRP3, caspase-1, NF-κβ, PAR- ) 1), ELISA (IL-18 and IL-1β) methods were examined. Thrombin activation and kidney function tests (albumin, creatinine, urea nitrogen and uric acid) were measured in serum samples. Statistical analysis results; Live weight gain in diabetic rats given boric acid; It was found to be lower than the control and STZ+insulin groups, and similar to the diabetes group. Fasting blood glucose levels of diabetic rats receiving boric acid treatment were different from the control and diabetes groups, but the STZ + insulin group showed close improvement. Tubular and glomerular women were found to be similar to the control and STZ+insulin group. Increased NLRP3, caspase-1, NF-κβ, IL-18, IL-1β, PAR-1 expressions and thrombin activation during the diabetes period were determined by boric acid application and healing rates, mainly by approximating STZ+insulin. It was observed that the closest result in the control and/or STZ+insulin group was in the STZ+BA200 group. In conclusion; Upregulation of PAR-1 mediates NLRP3 activation and boric acid exerts its anti-inflammatory effects where it exerts nephroprotective effects by inhibiting these signaling pathways.