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PPAR?-dependent increase of mouse urine output by gemfibrozil and fenofibrate.


ABSTRACT: While gemfibrozil and fenofibrate are prescribed for anti-dyslipidemia treatment, a rational basis for the use of these drugs for treatment of dyslipidemia with concurrent metabolic syndrome has not been established. In this study, wild-type and Ppar?-null mice were fed gemfibrozil- or fenofibrate-containing diets for 14 days. Urine output (24 h) was monitored, and urine, serum, and liver and kidney tissues were subjected to toxicity assessment. A 2-month challenge followed by a 2-week wash-out was performed for gemfibrozil to determine urine output and the potential toxicity. A therapeutically equivalent dose of gemfibrozil was more effective than fenofibrate in increasing urine output. This regulatory effect was not observed in Ppar?-null mice. In contrast, hepatomegaly induced by fenofibrate was more pronounced than that of gemfibrozil. No significant toxicity was observed in liver or kidney in the 2-month treatment with gemfibrozil. These data demonstrated PPAR? mediates the increased urine output by fibrates. Considering the relative action on hepatomegaly and the regulatory effect on urine output, gemfibrozil may be the preferable drug to increase urine output. These results revealed a new pharmacodynamic effect of clinically prescribed PPAR? agonists and suggested the potential value of gemfibrozil in modification of blood pressure.

SUBMITTER: Song D 

PROVIDER: S-EPMC6334299 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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PPARα-dependent increase of mouse urine output by gemfibrozil and fenofibrate.

Song Danjun D   Luo Min M   Dai Manyun M   Bu Shizhong S   Wang Weihua W   Zhang Burong B   Gonzalez Frank J FJ   Liu Aiming A  

Canadian journal of physiology and pharmacology 20160906 2


While gemfibrozil and fenofibrate are prescribed for anti-dyslipidemia treatment, a rational basis for the use of these drugs for treatment of dyslipidemia with concurrent metabolic syndrome has not been established. In this study, wild-type and Pparα-null mice were fed gemfibrozil- or fenofibrate-containing diets for 14 days. Urine output (24 h) was monitored, and urine, serum, and liver and kidney tissues were subjected to toxicity assessment. A 2-month challenge followed by a 2-week wash-out  ...[more]

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