Ectonucleotidase Activity in Smooth Muscle Tissues of Rats with a Valproate Model of Autism.

Ectonucleotidases play an important role in regulating the level of extracellular nucleotides and nucleosides and are an important part of the regulation of the effects of adenosine and ATP on adenosine and P2 receptors, respectively. We have previously established the ambiguous effect of P2 receptor agonists on the contractile activity of smooth muscle tissue in rats with the valproate model of autism. In this work, HPLC was used to evaluate the activity of ectonucleotidases in the smooth muscle tissues of the internal organs of rats with a valproate model of autism. The activity of ectonucleotidases was significantly higher in the smooth muscle tissues of the duodenum, vas deferens, and bladder, but lower in the ileum and uterus. The results obtained make it possible to compare the activity of ectonucleotidases identified here with changes in P2 receptor-mediated contractility of smooth muscle tissues revealed in our previous experiments.

Influence of oxidative stress on inducing micturition dysfunction following chronic infravesical obstruction and the protective role of an antioxidant diet - association of in vivo and in vitro studies in rats

OBJECTIVE: This study was developed to determine whether the generation of free radicals, induced by ischemia followed by reperfusion in a model of chronic intravesical obstruction in rats, would lead to damage in the detrusor. It also investigates the possible protective action of the flavonoid galangin on the tissue lesion induced by lipid peroxidation. MATERIALS AND METHODS: Twenty-one male rats were divided into three groups of seven animals each. Group A was subjected to a sham procedure; group B to partial obstruction of the bladder neck; and group C to partial obstruction of the bladder neck, but also received a diet rich in the flavonoid galangin. All the animals were subjected to urodynamic evaluation and then sacrificed. The bladders were sent for enzymatic tests. RESULTS: The urodynamic showed that group B developed significantly greater numbers of involuntary contractions of the detrusor, greater post-micturition residue and lower compliance. The group A presented TEAC levels greater than to the group B. Comparative analysis of group A, B and C demonstrated significantly greater malondialdehyde levels in group B in relation to groups A and C. The group B presented smaller contraction amplitudes than did groups A and C, in electrically stimulated contractions. CONCLUSIONS: That oxidative stress is implicated in the damage to the detrusor musculature following a period of chronic intravesical obstruction. We show, for the first time, that administration of an antioxidant prior to and following the start of chronic obstruction makes it possible to avoid the cellular lesions that cause detrusor dysfunction.

Effect of hydrogen peroxide on rabbit urinary bladder citrate synthase activity in the presence and absence of a grape suspension

PURPOSE: The etiology of obstructive bladder dysfunction includes free radical damage to mitochondria. Feeding rabbits a standardized grape suspension protects the ability of the bladder to contract and empty in part by preventing mitochondrial damage, thus maintaining smooth muscle and mucosal metabolism. The objective of the current study is to determine the direct effect of this grape suspension on the response of mitochondria to the oxidative effects of hydrogen peroxide. MATERIALS AND METHODS: Six male rabbits were anesthetized with sodium pentobarbital and the bladders excised. Four full thickness strips were obtained for contractile studies and the balance separated into smooth muscle and mucosa compartments by blunt dissection. The effect of hydrogen peroxide on the contractile response to field stimulation was quantitated. Each tissue was homogenized and the effects of increasing concentrations of hydrogen peroxide in the presence and absence of grape suspension on citrate synthase activity was determined. RESULTS: Citrate synthase activity was significantly higher in the mucosa than in the muscle. The grape suspension had no effect on control citrate synthase activity. However, the grape suspension provided significant protection of both smooth muscle and mucosal citrate synthase activity. CONCLUSIONS: These studies support the conclusion that the grape suspension provides direct protection of mitochondrial function.

Modulation of thymidine kinase activity: a biochemical strategy to enhance the activation of antineoplastic drugs

Thymidine kinase is a key enzyme responsible for the activation of several anticancer and antiviral drugs. As the first enzyme in the salvage pathway of thymidine, it is regulated by the feedback inhibition exerted by the end-product of the pathway, namely thymidine 5'-triphosphate. 5'-Aminothymidine is a non-toxic analogue of thymidine capable of interfering with this regulatory mechanism. In fact, it has been shown that 5'-aminothymidine increases the cytotoxicity and metabolism of various thymidine analogues currently in use of the clinic as antineoplastic agents. This mini-review article focuses in the evidence supporting the role of 5'-aminothymidine as a potential prototype drug for a new class of anticancer agents: drugs which affect the regulation of key metabolic pathways that determine the efficacy of agents with cytotoxic activity. The mechanism of action, antineoplastic activities and basis for selectivity in tissue culture models are also described