Jacobsen catalyst as a P450 biomimetic model for the oxidation of an antiepileptic drug

In this work, we investigated carbamazepine (CBZ) oxidation by 3-chloroperoxybenzoic acid (m-CPBA), tert-butyl hydroperoxide 70 wt.% (t-BuOOH) or hydrogen peroxide 30 wt.%, mediated by a salen complex in homogeneous medium or encapsulated in a polymeric matrix based on poly(dimethylsiloxane) (PDMS). The formation of carbarnazepine 10, 11-epoxide (CBZ-EP) is highly dependent on the oxidant, pH, solvent and co-catalyst. CBZ oxidation by m-CPBA, t-BuOOH and H2O2 is more efficient at low pH values, although the pH influence is small in the case of m-CPBA and t-BuOOH, in the entire pH range. This shows that the presence of substituents linked to the -OOH group of m-CPBA and t-BuOOH affects the catalytic activity of the studied system significantly. The encapsulated Jacobsen catalyst proved to be an efficient catalyst for carbarnazepine oxidation by the oxidants t-BuOOH and m-CPBA. However, the hybrid polymeric membrane acted as a barrier against the oxidant H2O2, preventing it from reaching the bulk of the membrane, making substrate oxidation impossible in this case. (C) 2007 Elsevier B.V. All rights reserved.2734167125926

Subsensitivity to insulin in adipocytes from rats submitted to foot-shock stress

We examined the effect of three daily foot-shock stress sessions on glucose homeostasis, insulin secretion by isolated pancreatic islets, insulin sensitivity of white adipocytes, and glycogen stores in the liver and soleus muscle of rats. Stressed rats had plasma glucose (128.3 +/- 22.9 mg/dL) and insulin (1.09 +/- 0.33 ng/mL) levels higher than the controls (glucose, 73.8 +/- 3.5 mg/dL; insulin, 0.53 +/- 0.11 ng/mL, ANOVA plus Fisher's test; p < 0.05). After a glucose overload, the plasma glucose, but not insulin, levels remained higher (area under the curve 8.19 &PLUSMN; 1.03 vs. 4.84 &PLUSMN; 1.33 g/dL 30 min and 102.7 &PLUSMN; 12.2 vs. 93.2 &PLUSMN; 16.1 ng/mL 30 min, respectively). Although, the area under the insulin curve was higher in stressed (72.8 &PLUSMN; 9.8 ng/mL) rats than in control rats (34.9 &PLUSMN; 6.9 ng/mL) in the initial 10 min after glucose overload. The insulin release stimulated by glucose in pancreatic islets was not modified after stress. Adipocytes basal lipolysis was higher (stressed, 1.03 &PLUSMN; 0.14; control, 0.69 &PLUSMN; 0.11 &mu;mol of glycerol in 60 min/100 mg of total lipids) but maximal lipolysis stimulated by norepinephrine was not different (stressed, 1.82 &PLUSMN; 0.35; control, 1.46 &PLUSMN; 0.09 &mu;mol of glycerol in 60 min/100 mg of total lipids) after stress. Insulin dose-dependently inhibited the lipolytic response to norepinephrine by up to 35% in adipocytes from control rats but had no effect on adipocytes from stressed rats. The liver glycogen content was unaltered by stress, but was lower in soleus muscle from stressed rats than in control rats (0.45 &PLUSMN; 0.04 vs. 0.35 &PLUSMN; 0.04 mg/100 mg of wet tissue). These results suggest that rats submitted to foot-shock stress develop hyperglycemia along with hyperinsulinemia as a consequence of insulin subsensitivity in adipose tissue, with no alteration in the pancreatic sensitivity to glucose. Foot-shock stress may therefore provide a useful short-term model of insulin subsensitivity.80878378