Abietic acid ameliorates nephropathy progression via mitigating renal oxidative stress, inflammation, fibrosis and apoptosis in high fat diet and low dose streptozotocin-induced diabetic rats

Background: Abietic acid (AA) has been reported to exhibit anti-inflammatory activity, however its protective effect against inflammation and its trigger factor i.e., oxidative stress and the related sequelae i.e., apoptosis and fibrosis in the kidney in diabetes mellitus (DM) is unknown. Purpose: To identify the ability of AA to mitigate the inflammatory and inflammation-related insults to the kidney in DM. Methods & Study design: Adult male rats were induced type-2 DM by feeding with a high-fat diet for twelve weeks followed by injection with a single dose of streptozotocin (STZ) (30 mg/kg/bw) intraperitoneally at twelve weeks. Following DM confirmation, AA (10 and 20 mg/kg/day) was given orally for another four weeks. Then the fasting blood glucose (FBG) and renal profile were determined and oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) tests were performed. A day after the last treatment, rats were sacrificed and kidneys were harvested and subjected for histopathological and molecular biological analysis. Results: AA treatment was found to reduce the FBG, serum urea and creatinine levels (p < 0.05) while improving the OGTT and ITT (p < 0.05) in diabetic rats. Besides, AA treatment also mitigated kidney histopathological changes, reduces kidney oxidative stress as reflected by reduced levels of RAGE and Keap1 but increased levels of kidney antioxidants Nrf2, SOD, CAT, GPX, HO-1 & NQO-1 (p < 0.05). Additionally, AA treatment also decreases kidney inflammation (NF-kB p65, IL-1 beta, IL-6, TNF-alpha and iNOS) and fibrosis (TGF-beta 1 and GSK-3 beta) (p < 0/05). Kidney apoptosis decreased as reflected by decreased levels of Bax, caspase-3 and caspase-9 while its anti-apoptosis Bcl-2 protein levels increased (p < 0.05). Conclusion: AA helps to mitigate nephropathy development in DM via counteracting oxidative stress, inflam-mation and apoptosis.