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

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.