Effect of 2,4 dinitrophenol on the rate of hepatic prostaglandin production.
The in vitro perfusion of livers under hypoxic conditions has been reported to produce hepatic cellular injury and to evoke endogenous prostaglandin (PG) synthesis. The present study investigates whether a cellular energy deficit in the presence of adequate tissue oxygenation is a stimulus for PG production. Rabbit livers were perfused for 3.5 hr in a nonrecirculating perfusion apparatus. Venous effluent lactic dehydrogenase (LDH), acid phosphatase (AP), lactic acid, and PG concentrations were measured. Perfusion pressure, liver weight, and oxygen consumption were also monitored. Control livers demonstrated stable values for all variables over a 3-hr observation period. Livers perfused with Krebs-Henseleit buffer containing 0.1 mM 2,4 dinitrophenol (DNP) demonstrated significant (P less than 0.05) increases in the rates of release of LDH, AP, and lactic acid. Neither perfusion pressure nor oxygen consumption was substantially altered by DNP treatment. However, the wet weight of the livers rose by 27% +/- 9% (P less than 0.05) at 180 minutes. The rate of release of PGF2 alpha rose from a control value of 0.07 +/- 0.02 to 1.28 +/- 0.43 ng/min/gm wet weight at 120 minutes. PGE2 increased from 0.16 +/- 0.02 in the control period to 2.08 +/- 0.58 ng/min/gm wet weight over the same time period. Similarly, the rate of release of the stable metabolite of prostacyclin rose from 0.20 +/- 0.04 ng/min/gm wet weight during the control period to 3.02 +/- 1.21 ng/min/gm wet weight 120 minutes after DNP. These results suggest that a pure cellular energy deficit as occurs during periods of hypoxia and circulatory shock is a potent stimulus for endogenous prostaglandin synthesis.
D019297:2,4-Dinitrophenol; D000818:Animals; D004140:Dinitrophenols / Q000633:toxicity*; D004734:Energy Metabolism; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010101:Oxygen Consumption; D011453:Prostaglandins / Q000096:biosynthesis*; D011817:Rabbits; D014475:Uncoupling Agents / Q000633:toxicity*
D004140:Dinitrophenols; D007773:Lactates; D011453:Prostaglandins; D014475:Uncoupling Agents; D019344:Lactic Acid; D019297:2,4-Dinitrophenol