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Antioxidants attenuate endotoxin-induced acute renal failure in rats
1Department of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Abstract:
Acute kidney dysfunction, manifested by a reduction in renal blood flow and in the glomerular filtration rate, is a common finding in septic shock. The pathogenetic mechanisms responsible for the renal dysfunction observed in the endotoxemic murine model are not completely understood. In this study, an attempt was made to halt the progressive renal dysfunction in the rats by administration of the antioxidants dimethylthiourea (DMTU) (50 mg/100 g) and superoxide dismutase (SOD) (0.4 mg/100 g) before endotoxin infusion (0.5 mg/100 g), or by inducing endotoxin tolerance. Renal function, assessed by creatinine, inulin, and p-aminohippuric acid clearance, nicotinamide adenine dinucleotide, and electrolyte reabsorption, was measured 4 hours after the endotoxin infusion. Renal function declined in all rats throughout the study period. However, the reduction in renal function was markedly slower in endotoxemic rats administered DMTU and SOD compared with untreated rats. Similar results were found following induction of endotoxin tolerance. These data suggest that DMTU, SOD, and endotoxin tolerance may be potentially beneficial in halting progressive renal damage associated with endotoxemia.
Insights
Antioxidants like dimethylthiourea (DMTU) and superoxide dismutase (SOD), along with endotoxin tolerance, slowed kidney dysfunction in septic shock models. These interventions show promise for protecting kidneys from endotoxemia-induced damage.
Area of Science:
- Nephrology
- Toxicology
- Immunology
Background:
- Sepsis-induced acute kidney dysfunction is common, impacting renal blood flow and glomerular filtration rate.
- Pathogenesis of renal dysfunction in endotoxemic models requires further understanding.
- Septic shock poses significant risks to renal function.
Purpose of the Study:
- To investigate the potential of antioxidants and endotoxin tolerance in mitigating renal dysfunction during endotoxemia.
- To evaluate the effects of dimethylthiourea (DMTU) and superoxide dismutase (SOD) on kidney function in an endotoxemic rat model.
- To assess whether inducing endotoxin tolerance can protect against endotoxemia-related kidney damage.
Main Methods:
- Administered DMTU and SOD antioxidants or induced endotoxin tolerance in rats prior to endotoxin infusion.
- Assessed renal function using creatinine, inulin, and p-aminohippuric acid clearance.
- Measured nicotinamide adenine dinucleotide levels and electrolyte reabsorption 4 hours post-endotoxin infusion.
Main Results:
- Renal function declined in all endotoxemic rats.
- Rats treated with DMTU and SOD exhibited a significantly slower decline in renal function compared to controls.
- Endotoxin tolerance induction also resulted in a slower progression of renal dysfunction.
- Electrolyte reabsorption and creatinine clearance were improved in treated groups.
Conclusions:
- Dimethylthiourea (DMTU), superoxide dismutase (SOD), and endotoxin tolerance demonstrate potential therapeutic benefits.
- These interventions may help to halt progressive renal damage associated with endotoxemia.
- Further research is warranted to explore clinical applications for preventing sepsis-related kidney injury.
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