Inhibition and stimulation of long-chain fatty acid oxidation by chloroacetaldehyde and methylene blue in rats

The effects of chloroacetaldehyde (CAA) and methylene blue, both alone and together, on mitochondrial metabolism, hepatic glutathione content, and bil e flow were investigated in rats. Oxidation of [1-C-14]palmitic acid, [1-C- 14]octanoic acid, and [1,4-C-14]succinic acid allowed for the differentiati on between carnitine-dependent long-chain fatty acid metabolism, medium cha in fatty acid oxidation, and citric acid cycle activity, respectively. CAA, a metabolite of the anticancer drug ifosfamide, which may be responsible f or ifosfamide-induced encephalopathy, inhibited palmitic acid metabolism bu t not octanoic or succinic acid oxidation, depleted hepatic glutathione, an d stimulated bile flow. Methylene blue, which is clinically used to either prevent or reverse ifosfamide-associated encephalopathy, markedly stimulate d palmitic acid oxidation either in the presence or absence of CAA, but did not affect the oxidation of octanoic and succinic acid or hepatic glutathi one. Taken together, this study demonstrates that CAA inhibits palmitic aci d metabolism. Methylene blue stimulates long-chain fatty acid oxidation, mo st likely by facilitating the translocation of fatty acids into mitochondri a, and compensates for the CAA effect in vivo.