Chronic Nuclear Factor-Kappa B Inhibition Prevents Experimental Aging Nephropathy

Area of Science:

• Nephrology
• Gerontology
• Pharmacology

Background:

• Aging nephropathy pathogenesis remains unclear.
• Intrarenal angiotensin II (AngII) and NF-κB/NLRP3 inflammasome pathways are implicated in chronic kidney disease progression.
• Investigating treatments to attenuate experimental aging nephropathy is crucial.

Purpose of the Study:

• To investigate the efficacy of losartan monotherapy and combined losartan and NF-κB inhibitor (PDTC) treatment in experimental aging nephropathy.
• To elucidate the role of AngII and NF-κB pathways in aging nephropathy.

Main Methods:

• Adult male Munich-Wistar rats were divided into four groups: 12-month-old controls, 15-month-old controls, 15-month-old rats treated with losartan, and 15-month-old rats treated with losartan and PDTC.
• Treatments were administered orally from 12 to 15 months of age.
• Renal function, histology, and molecular markers of inflammation and fibrosis were assessed.

Main Results:

• 15-month-old rats showed increased albuminuria, glomerulosclerosis, collagen deposition, myofibroblasts, AngII, and M1 macrophages, with reduced M2 macrophages.
• NF-κB pathway activation (TLR4, p65, IL-6) was evident, but NLRP3 inflammasome was not activated.
• Losartan alone reduced fibrosis markers but did not improve albuminuria or glomerulosclerosis.
• Combined losartan and PDTC treatment prevented all observed aging nephropathy abnormalities.

Conclusions:

• Simultaneous blockade of renal AngII and NF-κB pathway effectively prevented aging nephropathy progression in rats.
• This combined therapeutic strategy may offer a novel approach to mitigate age-related decline in kidney function.