Effect of acetaminophen on the progression of renal damage in adenine induced renal failure model rats

Life Sci. 2012 Dec 17;91(25-26):1304-8. doi: 10.1016/j.lfs.2012.09.018. Epub 2012 Oct 12.

Abstract

Aims: Acetaminophen is a safe antipyretic and analgesic drug within the clinically recommended dosage range, but overdose can cause fatal liver and or kidney damage. Most of the nonsteroidal anti-inflammatory drugs (NSAIDs) exert their analgesic effect via inhibition of cyclooxygenase, which also results in a reduction of renal blood flow. Therefore, the use of NSAIDs in pain treatment for chronic kidney disease (CKD) patients is of particular concern. Acetaminophen lacks the anti-inflammatory and anti-coagulatory properties of the NSAIDs. In this study, we investigate whether acetaminophen has an impact on the progression of renal failure.

Main methods: Acetaminophen (150mg/kg/day or 750mg/kg/day) or indomethacin (5mg/kg/day) was orally administered to adenine-induced chronic renal failure model rats for 4weeks. The plasma concentrations of acetaminophen and its metabolites were measured during the treatment period; renal function and oxidative stress in the rats were also monitored.

Key findings: Indomethacin significantly decreased the survival rate of renal failure model rats. In contrast, both low (150mg/kg) and high (750mg/kg) doses of acetaminophen improved the survival rate. The progression of renal failure was attenuated by acetaminophen (750mg/kg) after administration for 2weeks. The metabolites of acetaminophen were found to accumulate in plasma. Plasma glutathione concentration had significantly recovered after acetaminophen administration.

Significance: Acetaminophen has no effect on the progression of renal damage in adenine-induced renal failure model rats. This result is in part due to acetaminophen's antioxidant activity. These results suggest that acetaminophen is a suitable analgesic agent for treating CKD patients.

Publication types

  • Comparative Study

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / pharmacokinetics
  • Acetaminophen / pharmacology*
  • Adenine / toxicity
  • Administration, Oral
  • Analgesics, Non-Narcotic / administration & dosage
  • Analgesics, Non-Narcotic / pharmacokinetics
  • Analgesics, Non-Narcotic / pharmacology*
  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacokinetics
  • Antioxidants / pharmacology*
  • Disease Models, Animal
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Glutathione / blood
  • Indomethacin / pharmacology
  • Kidney Failure, Chronic / drug therapy*
  • Kidney Failure, Chronic / physiopathology
  • Male
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Survival Rate

Substances

  • Analgesics, Non-Narcotic
  • Antioxidants
  • Acetaminophen
  • Glutathione
  • Adenine
  • Indomethacin