Riboflavin and pyrroloquinoline quinone generate carbon monoxide in the presence of tissue microsomes or recombinant human cytochrome P-450 oxidoreductase (CPR); implications for possible roles in gasotransmission.

Riboflavin and pyrroloquinoline quinone generate carbon monoxide in the presence of tissue microsomes or recombinant human cytochrome P-450 oxidoreductase (CPR); implications for possible roles in gasotransmission. Can J Physiol Pharmacol. 2019 Dec 11;: Authors: Vukomanovic D, Jia Z, Nakatsu K, Smith GN, Ozolinš TRS Abstract Carbon monoxide (CO), an endogenously produced gasotransmitter, regulates inflammation and vascular tone, suggesting delivery of CO may be therapeutically useful for pathologies like preeclampsia where CO insufficiency are implicated. Our strategy is to identify chemicals that increase the activity of endogenous CO producing enzymes, including cytochrome P-450 oxidoreductase (CPR). Realizing both riboflavin and pyrroloquinoline quinone (PQQ) are relatively non-toxic, even at high doses, and they share chemical properties with toxic CO activators we previously identified, our goal was to determine whether riboflavin or PQQ could stimulate CO production. Riboflavin and PQQ were incubated in sealed vessels with rat and human tissue extracts and CO generation was measured with headspace-gas chromatography. Riboflavin and PQQ increased CO production ~ 60% in rat spleen microsomes. In rat brain microsomes, riboflavin and PQQ increased respective CO production ~four-fold and two-fold, compared to baseline. CO production by human placenta microsomes increased four-fold with riboflavin and five-fold with PQQ. In the pres...
Source: Canadian Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Can J Physiol Pharmacol Source Type: research