The carbochromene derivative AD6 reduces the TxB2/6-keto-PGF1 alpha ratio in cerebral cortex during hypoxia and recovery and leukotriene synthesis in brain tissue, in the rat.
Pretreatments of rats with the Carbochromene derivative AD6 (4 mg/kg i.p., 2 h before sacrifice) resulted in elevation of brain levels of 6-keto-PGF1 alpha in cerebral cortex under physiological conditions, had no effect on levels of TxB2 and 6-Keto-PGF1 alpha at 30 min of hypoxia (respiration of 5% O2 in N2) and prevented the accumulation of TxB2 occurring in brain at 5 min of recovery after hypoxia. In addition, the accumulation of LTC4 and B4 in brain slices incubated in the presence of the Ca++ ionophore A23187 and arachidonic acid, was reduced in samples obtained from pretreated rats. The drug, thus, had favourable effects on the 6-keto-PGF1 alpha/TxB2 ratio in normal conditions, as well as in conditions of altered oxygen supply. In addition it reduced the formation of compounds, the leukotrienes, which may exert pro-inflammatory activities on the cerebral microcirculation.
Bertazzo
A
A
Institute of Pharmacological Sciences, University of Milan, Italy.
Petroni
A
A
Sarti
S
S
Colombo
C
C
Galli
C
C
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism*; D000693:Anaerobiosis; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002866:Chromonar / Q000031:analogs & derivatives / Q000494:pharmacology*; D003374:Coumarins / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000378:metabolism*
D003374:Coumarins; D013189:SRS-A; D007975:Leukotriene B4; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C025945:cloricromen; D008084:Lipoxygenase; D002866:Chromonar