Effect of pioglitazone on plasma levels of phenytoin in rats

Introduction: Interaction between drugs represents a major clinical concern for health care professionals and their patients. Patients affected by both type 2 diabetes and epilepsy may be prescribed pioglitazone and an anti-epileptic drug such as phenytoin concurrently. The aim of this study was to consider the interaction of pioglitazone with phenytoin in an experimental model. According to the result of this study concurrent use of phenytoin and pioglitazone in clinic may cause therapeutic failure of phenytoin which may cause seizures and during seizures the cardiac function may be affected

Materials and Methods: Two groups of rats were treated for 30 days. In group 1 [control group] saline [10 ml/kg] and phenytoin [30 mg/kg] were administered daily by intragastric gavage. In group 2 [test group], pioglitazone [10 mg/kg] was administered daily 60 minutes before phenytoin [30 mg/kg]. Two hours after the last intragastric gavage, animals were anesthetized with ether and 2 ml of blood was drawn from the heart into a syringe containing Ethylenediaminetetraacetic [EDTA], and phenytoin concentration in rat plasma was determined by High performance liquid chromatography [HPLC].The study consisted of 2 groups of 10 male adult Wistar rats

Results: Compared with control group, concurrent use of pioglitazone and phenytoin was associated with significantly lower mean plasma concentrations of phenytoin: 2.08 +/- 0.25 micro g/ml VS 1.2 +/- 0.02 micro g/ml [p< 0.05]

Conclusion: Concurrent use of pioglitazone and phenytoin was associated with a significant decrease in plasma concentration of phenytoin in this experimental model. In clinic, this interaction may cause seizures and it has been shown that both cardiac and respiratory functions may affected by seizures

direct comparison of anti-ulcer effects of coenzyme Q10 and vitamin C on indomethacin-induced gastric ulcer in rat: a controlled experimental study

Indomethacin increases generation of mitochondrial reactive oxygen species [ROS] which have a crucial role in the indomethacin-induced gastric ulcer. Coenzyme Q10 has an antioxidant activity on mitochondria and cell membranes and protects lipids from oxidation and is essential for stabilizing biological membranes. Superoxide dismutase [SOD] acts as one of the defense mechanisms against free radicals. When the generation of ROS overwhelms, the antioxidant defense, lipid peroxidation of cell membrane occurs and cause cell damage. Male adult Wistar rats were divided into A and B groups. The rats in group A were then further divided into three subgroups of 6 animals each and received one of the following treatments: Animals in the first subgroup received saline. Animals in the second subgroup received saline and indomethacin. Animals in the third subgroup received vitamin C and indomethacin. The rats in group B were also further divided into 3 subgroups of 6 rats each and treated with one of the following treatments: Animals in first subgroup received 1% Tween 80 as vehicle. Animals In second subgroup received 1% Tween 80 and indomethacin. Animals in third subgroup received CoQ10 and indomethacin. Four hours after the last treatment, animals were killed by an overdose of ether and 2 ml blood was drawn from left ventricle into syringe containing EDTA [1mg/ml] and the stomachs removed were cut and gastric mucosal lesions were examined. Ulcer indexes were determined and SOD activity measured in plasma. Pre-treatment with both vitamin C and coenzyme Q10 was associated with attenuation of ulcer index and increased SOD activity comared with animals treated with indomethacine alone [p<0.001]. This effect of CoQ10 may be due to its electron donating property that inhibits the decrease in SOD activity in gastric tissue [replenishment of endogenous SOD] and inhibiting lipid peroxidation

Role of 5-hydroxytryptamine 1a receptors in 6-hydroxydopamine-induced catalepsy-like immobilization in rats: a therapeutic approach for treating catalepsy of parkinson's disease

We have shown that buspirone, a partial agonist of 5-hydroxytryptamine 1A [5-HT[1A]] receptors, improves motor dysfunctions induced by 6-hydroxydopamine [6-OHDA] and haloperidol in rats. The present work extends these findings by investigating the role of 5-HT[1A] receptors on catalepsy-like immobilization in rats, a model of Parkinson's disease. Catalepsy was induced by unilateral infusion of 6-OH-dopamine [8 micro g/2 micro L/rat] into the central region of the substantia nigra, compact part [SNc] and assayed by bar-test method 5, 60, 120 and 180 min after the drugs administration. The involvement of 5-HT[1A] receptors in 6-OHDA-induced catalepsy was studied through intraperitoneal [0.25, 0.5 and 1mg/Kg IP] and intrasubstantia nigra, compact part [10 micro g/rat, intra-SNc] injection of 8-hydroxy-2-[di-n-propylamino] tetralin [8-OHDPAT] as well as administration of 1-[2-methoxyphenyl]-4-[4-[2-pthalimmido] butyl] piperazine hydrobromide [0.1, 0.5 and 1 mg/Kg, NAN-190, IP]. NAN-190 [1 mg/Kg, IP] and 8-OHDPAT [1 mg/Kg, IP and 10 micro g/rat, intra-SNc] increased and decreased 6-OHDA-induced catalepsy respectively. In normal [non 6-OHDA-lesioned] rats, NAN-190 [1 mg/Kg, IP] increased the elapsed time in bar-test while 8-OHDPAT did not produce any significant effect. The anticataleptic effect of 8-OHDPAT [1 mg/Kg, IP] was reversed markedly by co-injection with NAN-190 [1 mg/Kg, IP]. These findings suggest that 5-HT1A receptors are involved in 6-OHDA-induced catalepsy-like immobilization

Synthesis of a novel siliconized analog of clofibrate [silafibrate] and comparison of their anti-inflammatory activities

Fibrates, as hypolipidemic drugs known as agonists of peroxisome proliferator-activated receptors, diminish inflammatory responses. Studies have shown that incorporation of a silicon atom into a drug structure improves its pharmacological potency, modifies its selectivity toward a given target, or changes its metabolic rate, in addition to increasing the lipophilicity of the compounds. A siliconized analog of clofibrate, ethyl-2-methyl-2-[4-[trimethylsilyl]phenoxy]propionate was synthesized, whereby the chlorine atom in the phenoxy ring was replaced by a trimethylsilyl group. The anti-inflammatory effects of the siliconized analog [silafibrate] were evaluated in an air-pouch model of inflammation and compared with those of clofibrate. Oral administration of both drugs produced a significant anti-inflammatory action by reducing carrageenan induced pouch leukocyte recruitment, exudates production, and granulated tissue weight. The silicon isostere of clofibrate has improved anti-inflammatory properties