Studies in vitro on the effects of 1H,2H,4H(5H)-octafluorocyclohexane and 1H,4H(2H)-nonafluorocyclohexane on enzymes and organelles.
A comparison has been made of the effect of 1H,2H,4H(5H)-octafluorocyclohexane, which is highly toxic (LD(50) 17mg./kg. in rats), and of 1H,4H(2H)-nonafluorocyclohexane, which is relatively non-toxic (LD(50)>440mg./kg. in rats), on the respiration of rat liver homogenates and mitochondria in vitro. 1H,2H,4H(5H)-Octafluorocyclohexane strongly inhibited the respiration of both homogenates and mitochondria, but neither compound had any significant effect on glycolysis or on glutamate dehydrogenase or NADH-cytochrome c reductase activity. 1H,2H,4H(5H)-Octafluorocyclohexane, however, caused a very marked inhibition of cytochrome oxidase activity, causing an almost complete lesion in this region of the respiratory chain. 1H,4H(2H)-Nonafluorocyclohexane was without effect in this respect. A marked decrease in turbidity of mitochondrial suspensions at 520nm. was caused by addition of both compounds, the effect being greater with 1H,2H,4H(5H)-octafluorocyclohexane. ATP, Mg(2+) and bovine serum albumin did not reverse these changes. Mitochondrial adenosine triphosphatase activity was increased twofold by the toxic compound, but only slightly by the non-toxic compound. Electron-microscopic examination of mitochondria treated with 1H,2H,4H(5H)-octafluorocyclohexane revealed gross morphological damage, whereas the effect of 1H,4H(2H)-nonafluorocyclohexane appeared to be merely to cause swelling. The results obtained account, to some extent at any rate, for the toxic effects of 1H,2H,4H(5H)-octafluorocyclohexane.
D000251:Adenosine Triphosphatases / Q000032:analysis; D000818:Animals; D003510:Cyclohexanes / Q000494:pharmacology*; D003720:Densitometry; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors; D005461:Fluorine / Q000494:pharmacology*; D005969:Glutamate Dehydrogenase / Q000032:analysis; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects; D008854:Microscopy, Electron; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats
D003510:Cyclohexanes; D005461:Fluorine; D005969:Glutamate Dehydrogenase; D003576:Electron Transport Complex IV; D000251:Adenosine Triphosphatases