Acetaminophen Attenuates Obesity-Related Renal Injury Through ER-Mediated Stress Mechanisms

Abstract

Background/Aims: Obesity is an independent risk factor for the development of kidney disease. The purpose of this study was to determine how obesity may contribute to renal damage and whether acetaminophen ingestion can diminish obesity-associated renal cell injury in the obese Zucker rat model. Methods: Male obese Zucker rats (4 weeks old, n=6) were treated with acetaminophen (30 mg / kg body weight / day) for 26 weeks. Age matched obese control (OC), obese vehicle (OV, 0.073 mL DMSO/kg/d), and lean Zucker rats (LC) were used to determine the effects of treatment and obesity. Results: Compared to lean control rats, renal lipid deposition, expression of the endoplasmic reticulum (ER) stress protein GRP78 and activation of the ER stress-related eIF2α-ATF4-CHOP, caspase 12, and JNK-MAPK signaling pathways were increased in the obese control and obese vehicle rats. These alterations were associated with the elevated renal cell apoptosis and urinary albumin excretion. Acetaminophen treatment decreased renal lipid deposition, ER-stress related signaling, apoptosis and albuminuria. Conclusion: These data suggest that the protective effects of low dose acetaminophen on renal injury are mediated, at least in part, through attenuation of ER stress.

Keywords

• Apoptosis
• Endoplasmic reticulum stress
• Lipotoxicity
• Obesity
• Acetaminophen
• Kidney