Acetaminophen attenuates glomerulosclerosis in obese Zucker rats via reactive oxygen species/p38MAPK signaling...

Area of Science:

• Nephrology
• Pharmacology
• Metabolic Syndrome Research

Background:

• Focal segmental glomerulosclerosis (FSGS) is a key lesion in metabolic syndrome-associated kidney disease, potentially leading to renal failure.
• Mechanisms of FSGS and effective prevention strategies remain limited.
• Obesity and metabolic syndrome increase the risk of kidney disease progression.

Purpose of the Study:

• To investigate the renoprotective effects of chronic low-dose acetaminophen in a metabolic syndrome kidney disease model.
• To elucidate the underlying mechanisms of acetaminophen's action on glomerulosclerosis and associated pathologies.

Main Methods:

• Obese Zucker rats, a model for metabolic syndrome, were treated with low-dose acetaminophen (30 mg/kg/day) for 6 months.
• Assessment included proteinuria, glomerulosclerosis, podocyte injury, inflammation, renal fibrosis, and expression of specific proteins.
• In vitro studies used human renal mesangial cells exposed to high glucose or hydrogen peroxide.

Main Results:

• Acetaminophen treatment attenuated proteinuria, glomerulosclerosis, podocyte injury, and inflammation in obese rats.
• It reduced renal fibrosis and profibrotic factors (fibronectin, CTGF, TGF-β).
• Acetaminophen decreased inflammatory markers (MCP-1) and oxidative stress markers (GSH reductase, Nrf2), while increasing GSH synthetase, and reduced p38MAPK hyperphosphorylation.

Conclusions:

• Chronic low-dose acetaminophen demonstrates significant renoprotective effects in a metabolic syndrome kidney disease model.
• The protective mechanisms involve diminished oxidative stress and p38MAPK signaling.
• Acetaminophen represents a potential therapeutic strategy for preventing or mitigating kidney disease associated with metabolic syndrome.