LCZ696 mitigates diabetic-induced nephropathy through inhibiting oxidative stress, NF-κB mediated inflammation and glomerulosclerosis in rats

• DOI: 10.7717/peerj.9196
• Publication Date: 2020-06-19T10:34:46Z
• Authors: Mohamed Mohany; Ahmed Z. Alanazi; Faleh Alqahtani; Osamah M. Belali; Mohammed M. Ahmed; Salim S. Al-Rejaie
• Keywords: TBARS; Glomerulosclerosis

Diabetic nephropathy (DN) is among the most common microvascular complications of diabetes resulting in end-stage renal disease and therefore search for candidates which can ameliorate kidney function needed simultaneously with standard diabetic pharmacotherapy. The current study was aimed to investigate effect long term sacubitril/valsartan therapy (LCZ696) rats assess its ameliorative impact against various pathological parameters such as oxidative stress, inflammation glomerulosclerosis associated chronic DN.A single dose (60 mg/kg/day) STZ used induce type 1 adult male wistar rats. 2 weeks after induction, these were treated orally valsartan (31 mg/kg) or LCZ696 (68 6 weeks. At end treatment period, serum samples collected analyzed. levels glucose, insulin, urea, creatinine, TNF-α, IL-1β, IL-6 IL-10 estimated. In tissue homogenate, inflammatory markers IL-6, NF-kB along stress biomarkers including thiobarbituric acid-reacting substances (TBARs), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), peroxidase (GPx), S-transferase (GST) assessed. Histological changes observed kidney.Time course withLCZ696 resulted significant reduction urea creatinine (P < 0.05). Additionally, showed a diminution (TNF-α, IL-6) increment anti-inflammatory (IL-10) cytokines Tissue homogenate extracted from revealed substantial sufficient restoration anti-oxidant enzyme Finally, histological sections kidney, prevention injury limited necrosis cells infiltration.Present data suggest that has therapeutic potential restrict DN progression through inhibiting inflammation, glomerulosclerosis.