In summary, following a single oral dose of DCA to laboratory rats, peak hepatic tissue DCA concentration occurred at 3 hr. When given chronically for 7 days, DCA caused activation of the pyruvate dehydrogenase complex which returned to basal activity 24 hr following the final dose. Hepatic tissue DCA concentrations were maximally increased at 3 hr following the final dose, and the drug was eli...

Abstract Introduction Advanced radiation therapy delivery techniques require greater understanding of various planning sequences and methods. The aim this study is to determine a class solution that finds the best possible technique deliver for stereotactic radiosurgery between dynamic conformal arc (DCA) using options such as DCA, DCA + SSO (segment shape optimization), VDR (variable dose rate...

OBJECTIVE To investigate the effects of 3,4-dichloroaniline (3,4-DCA) on activities of testicle enzymes as biological markers in rats. METHODS Fifty male rats were randomly divided into 5 groups (n=10). One group was left untreated and used as a solvent control (administered orally by corn oil), while the other 4 groups were treated with 3, 4-DCA. Corn oil was used as a solvent, and 3,4-DCA w...

We studied the pharmacokinetics of dichloroacetate (DCA) in naive rats and rats depleted of glutathione S-transferase-zeta (GST-zeta), at doses approaching human daily exposure levels. We also compared in vitro metabolism of DCA by rat and human liver cytosol. Jugular vein-cannulated male Fischer-344 rats received graded doses of DCA ranging from 0.05 to 20 mg/kg (intravenously or by gavage), a...

The endogenous bile acid metabolite 1β-hydroxy-deoxycholic acid (1β-OH-DCA) excreted in human urine may be used as a sensitive CYP3A biomarker in drug development reflecting in vivo CYP3A activity. An efficient and stereospecific enzymatic synthesis of 1β-OH-DCA was developed using a Bacillus megaterium (BM3) cytochrome P450 (P450) mutant, and its structure was confirmed by nuclear magnetic res...

Impairment of gut barrier is associated with a fat-rich diet, but mechanisms are unknown. We have earlier shown that dietary fat modifies fecal bile acids in mice, decreasing the proportion of ursodeoxycholic acid (UDCA) vs. deoxycholic acid (DCA). To clarify the potential role of bile acids in fat-induced barrier dysfunction, we here investigated how physiological concentrations of DCA and UDC...

The aim of this study was to investigate the effects of deoxycholic acid (DCA) on the contractions of rat proximal colonic smooth muscle (PCSM) in vitro. The contractile response of rat PCSM strips was tested using a polyphysio-graph. The whole cell patch-clamp technique was also used in rat colonic smooth muscle cells (SMCs) isolated by an enzymatic procedure to record the L-type calcium curre...

Even in the presence of oxygen most cancer cells convert glucose to lactate via pyruvate instead of performing oxidative phosphorylation (aerobic glycolysis-Warburg effect). Thus, it has been considered to shift pyruvate - the metabolite of aerobic glycolysis - to acetylCoA by activation of pyruvate dehydrogenase (PDH). AcetylCoA will then be metabolized by oxidative phosphorylation. Therefore,...

Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, has anti-tumor properties in various carcinoma models. Diisopropylamine dichloroacetate (DADA), an over-the-counter drug for chronic liver disease, is a derivative of DCA. To date, few studies have evaluated the anticancer potential of DADA in breast cancer. In this study, MDA-MB-231 cells, a breast adenocarcinoma cell line, ...

BACKGROUND Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis responds to immunnotherapy, and approximately 80% of patients with this disorder fully recover or have only minor sequelae. Brain magnetic resonance imaging (MRI) does not show a specific abnormality, but some patients have progressive cerebral atrophy. The cerebral atrophy can become reversible after clinical improvement. ...