Effect of lidocaine on hepatic prostanoid production in vitro following 2,4-dinitrophenol administration.
The uncoupling of oxidative phosphorylation with 2,4-dinitrophenol (DNP) stimulates prostacyclin production in the isolated, perfused rabbit liver. This study determines the effect of a clinically used drug, lidocaine, on DNP induced cellular injury and prostanoid biosynthesis in vitro. Livers were perfused with buffer alone, buffer containing 10 microM DNP or lidocaine, or buffer containing both 10 microM DNP and 10 microM lidocaine. DNP treatment significantly increased lactic dehydrogenase and acid phosphatase activity in the effluent perfusate, indicating a moderate degree of cellular injury. These enzyme changes were exacerbated by lidocaine. The rate of release of thromboxane B2 by the perfused liver was not significantly affected by DNP or lidocaine treatment. In contrast, DNP significantly stimulated 6-keto PGF1 alpha production from a control period value of 177 +/- 40 to 2,938 +/- 979 picograms/min/g wet weight after 180 minutes of perfusion. The addition of 10 microM lidocaine to the DNP treatment resulted in a significant attenuation in the rate of endogenous 6-keto PGF1 alpha release to values not different from those of the sham plus vehicle-treated group. In livers receiving lidocaine alone, there was a slight but significant increase in the rate of 6-keto PGF1 alpha synthesis. These data demonstrate that lidocaine can inhibit injury related activation of the arachidonic acid cascade in hepatic tissue. The addition of lidocaine to the perfusate of the injured livers also resulted in a more severe degree of cellular injury. The relationship between these two events remains to be determined.
D019297:2,4-Dinitrophenol; D000818:Animals; D004140:Dinitrophenols / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology*; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010477:Perfusion; D011453:Prostaglandins / Q000096:biosynthesis*; D011460:Prostaglandins F / Q000096:biosynthesis; D011817:Rabbits; D013929:Thromboxane B2 / Q000096:biosynthesis
D004140:Dinitrophenols; D011453:Prostaglandins; D011460:Prostaglandins F; D013929:Thromboxane B2; D008012:Lidocaine; D011464:Epoprostenol; D007770:L-Lactate Dehydrogenase; D019297:2,4-Dinitrophenol; C100006:prostaglandin F1