Quercetin in association with moderate exercise training attenuates injuries induced by experimental diabetes in sciatic nerves.

Diabetic neuropathy (DN) is a frequent, serious and debilitating chronic complication of diabetes mellitus (DM). Hyperglycemia, oxidative and nitrosative stress are involved in causing nerve damage in several animals, humans and experimental models of diabetes. This study was designed to investigate the synergistic cumulative neuroprotective effect of quercetin administration and moderate exercise training on sciatic nerves injuries in streptozotocin (STZ)-diabetic rats. DM was induced in Wistar rats by intraperitoneal administration of STZ (60 mg/kg). The diabetic rats received quercetin (30 mg/kg body weight/day) and performed an exercise training program (30 minutes/day, 5 days/week) for 5 weeks. Various biochemical parameters of oxidative and nitrosative stress were determined and histopathological evaluations were performed from sciatic nerves. Diabetic rats showed significantly increased oxidative and nitrosative stress parameter levels in the sciatic nerves. Diabetic trained rats treated with quercetin exhibited a significantly reduced hyperglycemia and its metabolic abnormalities induced by intraperitoneal administration of STZ. Histological alterations of the sciatic nerves induced after STZ administration were restored by administration of quercetin. Quercetin administration in association with moderate exercise training not only attenuated the diabetic condition but also restored sciatic nerves injuries by controlling hyperglycemia to down-regulate the generation of free radicals, as well as the elevation of antioxidant enzymes.

Protective effects of Quercetin and chronic moderate exercise (training) against oxidative stress in the liver tissue of streptozotocin-induced diabetic rats.

Background To investigate the protective effects of Quercetin administration associated with chronic moderate exercise (training) on oxidative stress in the liver in streptozotocin-induced diabetic rats. Methods Diabetic rats that performed exercise training were subjected to a swimming training program (1 hour/day, 5 days/week, 4 weeks). The diabetic rats received natural antioxidant, Quercetin (20 mg/kg body weight/day) for 4 weeks. At the end of the study, all animals were sacrificed and liver samples were collected for estimation: some oxidative stress markers (malondialdehyde, MDA and protein carbonyls groups, PC), the activity of antioxidant enzymes (superoxide dismutase, SOD and catalase, CAT), reduced glutathione (GSH) level and reduced (GSH) and oxidized (GSSG) glutathione ratio. Results Diabetic rats submitted to exercise training showed significantly increased the oxidative stress markers (MDA and PC) and a reduction of antioxidant enzyme (SOD and CAT) activity, GSH level and GSH/ GSSG ratio in hepatic tissues. A decrease in the levels of oxidative stress markers associated with elevated activity of antioxidant enzymes, the GSH level and GSH/GSSG ratio in the hepatic tissue were observed in Quercetin-treated diabetic trained rats. Conclusions These findings suggest that Quercetin administration in association with chronic moderate exercise exerts a protective effect in diabetes by attenuating hyperglycemia-mediated oxidative stress in hepatic tissue.

Robust anti-arrhythmic efficacy of verapamil and flunarizine against dofetilide-induced TdP arrhythmias is based upon a shared and a different mode of action.

BACKGROUND AND PURPOSE: The high predisposition to Torsade de Pointes (TdP) in dogs with chronic AV-block (CAVB) is well documented. The anti-arrhythmic efficacy and mode of action of Ca(2+) channel antagonists, flunarizine and verapamil against TdP were investigated. EXPERIMENTAL APPROACH: Mongrel dogs with CAVB were selected based on the inducibility of TdP with dofetilide. The effects of flunarizine and verapamil were assessed after TdP and in different experiments to prevent dofetilide-induced TdP. Electrocardiogram and ventricular monophasic action potentials were recorded. Electrophysiological parameters and short-term variability of repolarization (STV) were determined. In vitro, flunarizine and verapamil were added to determine their effect on (i) dofetilide-induced early after depolarizations (EADs) in canine ventricular myocytes (VM); (ii) diastolic Ca(2+) sparks in RyR2(R4496+/+) mouse myocytes; and (iii) peak and late I(Na) in SCN5A-HEK 293 cells. KEY RESULTS: Dofetilide increased STV prior to TdP and in VM prior to EADs. Both flunarizine and verapamil completely suppressed TdP and reversed STV to baseline values. Complete prevention of TdP was achieved with both drugs, accompanied by the prevention of an increase in STV. Suppression of EADs was confirmed after flunarizine. Only flunarizine blocked late I(Na). Ca(2+) sparks were reduced with verapamil. CONCLUSIONS AND IMPLICATIONS: Robust anti-arrhythmic efficacy was seen with both Ca(2+) channel antagonists. Their divergent electrophysiological actions may be related to different additional effects of the two drugs.

[Manifestations of visceral and ocular symptoms of toxocariasis in a 6-year-old boy]. / Pojava visceralne i okularne klinicke slike toksokarijaze kod sestogodisnjeg decaka.

In the past 10 years we have examined 137 cases of toxocariasis, predominantly in children. Three cases were with unilateral ocular involvement. The article reviews a 6-year-old boy with left side strabismus and granulomatous chorioretinitis. Laboratory examinations revealed blood eosinophylia 24% and IgG against Toxocara canis larvae in titer 1:320 by indirect immunofluorescent assay. In epidemiologic anamnesis we concluded that about 4, 5-year-long geophagia was the source of infection.

Apoptosis and free radicals.

Free radicals that appear during physiological processes may lead to apoptosis in some pathological conditions when antioxidant capacity of the tissue is surpassed. Additionally, free radicals are involved in the control of apoptosis; antioxidant agents suppress apoptosis induced by a variety of stimuli. The possibility that apoptosis is regulated by modulation of the levels of free radicals is discussed.

Apoptosis II: Apoptosis in the pathogenesis and treatment of diseases.

This review presents the implications of abnormal regulation of apoptosis in the pathogenesis of a variety of diseases, some of them characterized by a failure of cells to undergo apoptosis, and the others characterized by cell loss. The new perspectives in the therapy of such diseases by developing therapeutic agents that increase or decrease the susceptibility of particular cells to apoptosis are also reviewed.

Apoptosis, I: General considerations.

This review tried to offer a basis for properly integrating genetic, biochemical, and cellular indicators of apoptosis in order to facilitate a better understanding of the control and mechanisms of apoptosis.