"a reduced all-trans retinoic acid inactivation process after 13-cis retinoic acid treatment as compared with treatment with all-trans retinoic acid"
"De novo mRNA expression of cytochrome P450 1A1, a major xenobiotic metabolizing enzyme, in SZ95 sebocytes was induced by all-trans retinoic acid, but not by 13-cis retinoic acid."
"Both 13-cis retinoic acid and all-trans retinoic acid suppressed mRNA expression of cytochrome P450 1A2."
It is shown here that bovine liver membranes, but not supernatant fractions, can isomerize all-trans-retinoic acid into 9-cis-retinoic acid and 13-cis-retinoic acid.
"It had previously been shown that S2 cells and COS-1 cells could isomerize all-trans-retinoic acid to generate 9-cis-retinoic acid and 13-cis-retinoic acid [11-13]."
-"Thus, after the subtraction of 13-cis-RA formed from the controls (1.0 ng), the incuba- tion of intestinal mucosa homogenates with all-trans-RA (26 ng) resulted in the formation of 2.8 to 8.3 ng of 13- cis-RA which corresponded to formation of 0.1 to 0.2 ng 13-cis-RAlh per mg protein"
They say in the last article that both all-trans-RA & 13-cis-RA (accutane) level are reduced by fasting, but that's kinda predictable..
Maybe accutane caused a modification of the intestine who synthetise/convert in excess all-trans-RA (in our case when we took 13-cis-RA for more than 6month, i believe in their trial it was just 1-2weeks)? It is known that the intestines adapt to changes (in the case of the flora who isn't affected directly i think). We took at least 100 lifetime dose of this natural occuring 13-cis-RA in only 6month, i find that strange that all is simply expelled in only 2month after treatment..
But wtf is happening with those isomerization, all-trans convert into 13-cis, then the intestine (& others cells of the body) convert it back to all-trans. Plus, both of them are suppressing one of their conjugation enzyme (CYP1A2) and only all-trans induced CYP1A1. Its impossible to mesure exactly if all accutane (13-cis-RA have been back to normal levels in all part of the body (not only bloodstream) in those conditions. There is something strange about those retinoic acids...
The big question is what the purpose of this naturally occuring 13-cis-RA? nobody knows... And if that was the way of the body to handle the all-trans-RA ? to disable it when it doenst need trans-RA anymore and to retransform it back when he want. Maybe this so high dosage of 13-cis-RA broked this system and maked all-trans-RA out of control.. idk...
I'm considering myself almost cured of all the effects of accutane but i find really annoying to not know precisely how it worked, i'm still searching...
Just remembered something, for those who got hair loss, it can be fixed with castor oil for some people. Castor oil can help detoxification of any part of the body, you can put it anywhere to help to reduce pain or symptoms.
Edited by anonyy, 22 November 2013 - 12:02 AM.