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

Daisuke Kadowaki, Satomi Sumikawa, Kanami Arimizu, Kazuaki Taguchi, Kenichiro Kitamura, Yoichi Ishitsuka, Yuki Narita, Tetsumi Irie, Victor Tuan Giam Chuang, Toru Maruyama, Masaki Otagiri, Sumio Hirata

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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 (150 mg/kg/day or 750 mg/kg/day) or indomethacin (5 mg/kg/day) was orally administered to adenine-induced chronic renal failure model rats for 4 weeks. 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 (150 mg/kg) and high (750 mg/kg) doses of acetaminophen improved the survival rate. The progression of renal failure was attenuated by acetaminophen (750 mg/kg) after administration for 2 weeks. 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.

Original languageEnglish
Pages (from-to)1304-1308
Number of pages5
JournalLife Sciences
Volume91
Issue number25-26
DOIs
Publication statusPublished - 2012 Dec 17
Externally publishedYes

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Keywords

  • Acetaminophen
  • Adenine
  • Antioxidant
  • Metabolite
  • Renal failure

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Kadowaki, D., Sumikawa, S., Arimizu, K., Taguchi, K., Kitamura, K., Ishitsuka, Y., Narita, Y., Irie, T., Chuang, V. T. G., Maruyama, T., Otagiri, M., & Hirata, S. (2012). Effect of acetaminophen on the progression of renal damage in adenine induced renal failure model rats. Life Sciences, 91(25-26), 1304-1308. https://doi.org/10.1016/j.lfs.2012.09.018