Nicotinamide and heat preconditioning - Effects on hepatic HSP70, carbohydrate and oxidative disturbances in STZ-induced diabetic rats.

OBJECTIVE: Nicotinamide (NA) is known to have antioxidant potential and partially to protect insulin-secreting cells against diabetogenic agent STZ (streptozotocin). In a combination to heat stress (HS), NA is also known to induce heat-shock proteins (HSPs) production. Heat preconditioning (HP) and HSPs have cytoprotective effects against development of cellular injury caused by application of subsequent stressor. We aimed to determine if pretreatment with NA and HP (as HSP70 -inducers) can affect STZ-induced diabetic disturbances in rats. METHODS: NA-pretreatment (250 mg/kg b.w., 7 days) and heat preconditioning (41 ± 1 °C, 45 min) of diabetic rats was performed. The changes in hepatic carbohydrate- and antioxidative-related enzymes and substrates were investigated. RESULTS: NA-pretreatment, alone or in combination with HS, resulted in significant increase of HSP70 concentration in the liver of control and diabetic rats. Compared to diabetic controls, pretreatment with NA, in combination with HP, resulted in decrease of blood and liver glucose, increase of glycogen and glucose-6-phosphate level, increase of glycogenolytic/glycolytic enzymes, decrease of gluconeogenic enzymes, as well as an increase of glutathione content and glutathione peroxidase, decrease of glutathione reductase and catalase activities. CONCLUSIONS: NA is a potent HSP70 coinducer, alone or in a combination with HS in the liver of both control and diabetic rats. Pretreatment with NA, accompanied by HP, has a pronounced corrective effect on STZ-induced diabetes disturbances in the key hepatic carbohydrate- and antioxidative-related parameters. It seems that this corrective effect is based on the increased production of hepatic HSP70.

Effects of Rosuvastatin Versus Atorvastatin, Alone or in Combination, on Lipoprotein (a).

BACKGROUND: There are little evidences about the therapeutic efficacy of different lipid-lowering agents in the reduction of elevated lipoprotein(a) [Lp(a)]. OBJECTIVE: testing the effect of different lipid-lowering agents on elevated Lp(a). METHODS: prospective interventional study performed in patients with CAD, or high CAD risk, with Lp(a), >50 mg/dL. Lp(a), total cholesterol (C), HDL-C, LDL-C, triglycerides (TGs), apolipoprotein (Apo) A1, Apo B, enzymes of myocyte and hepatic injury were comparatively analyzed between 4 lipid-lowering strategies: rosuvastatin (R group) 40 mg, atorvastatin (A group) 80 mg, atorvastatin 40 mg add-on micronized fenofibrate (A+F group), and atorvastatin 40 mg add-on 1 g extended-release niacin (A+ERN group). Comparison was made for their therapeutic efficacy on Lp(a), and safety. RESULTS: 87 patients with mean Lp(a) 94.6 ± 39.6 mg/dL were analyzed. Groups: 25 patients in the R, 22 in the A, 20 in the A+F and 20 in A+ERN group. Significant reduction in all lipid fractions in all treatment groups was reported after 6 months. The average reduction of Lp(a) was 15.9 ± 21.0 mg/dL, with: 18.2 ± 24.8 (P = 0.001) in the R group, 17.3 ± 10.4 (P = 0.001) in A+F, 19.5 ± 10.9 (P = 0.001) in A+ERN and the lowest in the A group (11.24 ± 22.91, P = 0.032). No adverse effects were observed in any of the treatment groups. CONCLUSIONS: When compared with atorvastatin, it seems that rosuvastatin can achieve more significant decrease of Lp(a).The efficacy of the second one can be increased by adding fibrate or ERN.