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


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.


RESULTS
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.


CONCLUSIONS
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.
Center for Clinical Pharmaceutical Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan.
Daisuke
D
Kadowaki
Satomi
S
Sumikawa
Kanami
K
Arimizu
Kazuaki
K
Taguchi
Kenichiro
K
Kitamura
Yoichi
Y
Ishitsuka
Yuki
Y
Narita
Tetsumi
T
Irie
Victor Tuan Giam
VT
Chuang
Toru
T
Maruyama
Masaki
M
Otagiri
Sumio
S
Hirata
D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000225:Adenine / Q000633:toxicity; D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000097:blood; D007213:Indomethacin / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate
D018712:Analgesics, Non-Narcotic; D000975:Antioxidants; D000082:Acetaminophen; D005978:Glutathione; D000225:Adenine; D007213:Indomethacin