Low doses of fenofibrate and bezafibrate stimulate renal 2-oxoglutarate dehydrogenase (2-OGDH) in protein-restricted rats

• Authors: Malgorzata E. Knapik-Czajka , Jagoda M. Drag , Anna Gawedzka
• Languages of publication: EN

Abstracts

EN

2-oxoglutarate dehydrogenase (2-OGDH) is the key regulatory enzyme of cell metabolism. It has been previously demonstrated that in rats subjected to protein restriction low, clinically relevant doses of fibrates up-regulate liver 2-OGDH and promote 2-oxoglutarate catabolism. The aim of the present study was to evaluate the effect of low doses of fenofibrate and bezafibrate on renal 2-OGDH complex in rats fed low-protein chow. Fibrates were administrated for 14 days to Wistar male rats at one daily doses of 5, 10 and 20 mg/kg b.wt./day. The 2-OGDH activity was assayed spectrophotometrically. The mRNA levels for 2-OGDH catalytic subunits (E1 and E2) and PPARα were quantified by means of semi-quantitative reverse-transcription-PCR. 2-OGDH activity increased in response to administration of fenofibrate and bezafibrate (by 11, 24, 32% and 9, 12, 21%, respectively). The difference was statistically significant for the doses of 10 and 20 mg/kg b.wt of fenofibrate (p<0.001) and the highest dose of bezafibrate (p<0.05). Stimulation of 2-OGDH was not accompanied by changes in mRNA levels for E1 and E2. In addition, mRNA level for PPARα did not change. It is conceivable that fibrate-induced stimulation of 2-OGDH activity can affect renal metabolism and contribute to changes in kidney functions.

Keywords

EN

2-oxoglutarate dehydrogenase; Fenofibrate; Bezafibrate; kidney

• Journal: Acta Poloniae Pharmaceutica - Drug Research
• Year: 2020
• Volume: 77
• Issue: 2
• Pages: 281-288

Dates

published

2020-04-29

Contributors

author

Malgorzata E. Knapik-Czajka

author

Jagoda M. Drag

author

Anna Gawedzka

Identifiers

DOI

10.32383/appdr/118535