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Hypolipidemic effect of a pro-drug containing nicotinic acid in rats

100%

Filip C., Albu E., Gheorghita N., Ghitler N., Mocanu G., Nechifor M.

Open Medicine

2006

vol. 1

issue 4

348-355

We studied the release of nicotinic acid from a macromolecular pro-drug containing niacin bound to a polymeric support of dextran. Using a modified High-performance Liquid Chromatography (HPLC) method to provide an improved separation between nicotinic acid and its metabolites, we compared the plasma levels of nicotinic acid 24 h after administration of the pro-drug or a similar dose of unbound nicotinic acid to rats. Nicotinic acid exerts a number of pharmacological activities among which is the hypolipidemic effect. To determine the hypolipidemic effect of the pro-drug, we measured the triglyceride levels and examined the correlation with the plasma levels of nicotinic acid.Starting 6 h after administration of the pro-drug, the plasma levels of nicotinic acid were high enough to cause a decrease in the triglyceride level. These results suggest that nicotinic acid was gradually released from the polymeric support, leading to the sustained presence of the active substance and, therefore, a reduction in the level of triglycerides.

Hyperhomocysteinemia’s effect on antioxidant capacity in rats

84%

Filip C., Albu E., Zamosteanu N., Irina M., Silion M., Jerca L., Gheorghita N., Costel M.

Open Medicine

2010

vol. 5

issue 5

620-626

Hyperhomocysteinemia represents elevated homocysteine (Hcys) concentrations in blood above the normal range. In humans, the normal range of homocysteine is 5.0–15.9 mM/ml. High levels of homocysteine disturb the normal epithelial functions and correlate with cardiovascular diseases even at slightly increased concentrations. In homocysteine metabolism, vitamins play an important role. The mechanism through which homocysteine triggers these effects is not yet elucidated, but the involvement of reactive species may be the answer. It is not known whether the intra- or extracellular antioxidant system is more affected by elevated homocysteine levels. We studied the effects of hyperhomocysteinemia on the intra- and extracellular antioxidant defense systems in two different types of diet in rats. Type I was food with low folic acid and vitamin B12 content and type II was food with normal amounts of these two vitamins. Hyperhomocysteinemia was experimentally induced by oral administration of methionine 2 mg/kg body weight, single daily dose, for a 15-day period. Plasma concentrations of homocysteine were measured using an HPLC method. In the response of the intracellular antioxidant defense system against hyperhomocysteinemia, we determined the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in red blood cells, using RANDOX kits for manual use. For the extracellular response we determined the plasma total antioxidant status (TAS) also using a RANDOX kit for manual use. Our data show that methionine load induces hyperhomocysteinemia despite normal vitamin supply in rats. SOD activity rose with simultaneous decrease in GPx activity independently of diet; this might suggest that the intracellular defense system was disturbed by the rise in homocysteine level. TAS decrease suggests that the extracellular antioxidant defense was also affected. We assume that hyperhomocysteinemia is directly linked to reactive species generation and the intracellular space seems to be more affected than the extracellular one.

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2 Open Medicine

1 2010

1 2006

2 Albu E.

2 Filip C.

2 Gheorghita N.

1 Costel M.

1 Ghitler N.

1 Irina M.

1 Jerca L.

1 Mocanu G.

1 Nechifor M.

1 Silion M.

1 Zamosteanu N.

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Hypolipidemic effect of a pro-drug containing nicotinic acid in rats

Hyperhomocysteinemia’s effect on antioxidant capacity in rats