Beneficial role of vanillin, a polyphenolic flavoring agent, on maneb-induced oxidative stress, DNA damage, and liver histological changes in Swiss albino mice.

Vanillin, a widely used flavoring agent, has antimutagenic and antioxidant properties. The current study was performed to evaluate its beneficial role against hepatotoxicity induced by maneb, a dithiocarbamate fungicide. Mice were divided into four groups of six each: group 1, serving as negative controls which received by intraperitoneal way only distilled water, a solvent of maneb; group 2, received daily, by intraperitoneal way, maneb (30 mg kg-1 body weight (BW)); group 3, received maneb at the same dose of group 2 and 50 mg kg-1 BW of vanillin by intraperitoneal way; and group 4, serving as positive controls, received daily only vanillin. After 10 days of treatment, mice of all groups were killed. Our results showed that vanillin significantly reduced the elevated hepatic levels of malondialdehyde, hydrogen peroxide, and advanced oxidation protein product and attenuated DNA fragmentation induced by maneb. In addition, vanillin modulated the alterations of antioxidant status: enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) and nonenzymatic (reduced glutathione, nonprotein thiol, and vitamin C) antioxidants in the liver of maneb-treated mice. This natural compound was also able to ameliorate plasma biochemical parameters (aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase, alkaline phosphatase, total bilirubin, and total protein). The protective effect of vanillin was further evident through the histopathological changes produced by maneb in the liver tissue. Thus, we concluded that vanillin might be beneficial against maneb-induced hepatic damage in mice.

Penconazole alters redox status, cholinergic function, and membrane-bound ATPases in the cerebrum and cerebellum of adult rats.

Pesticides exposure causes usually harmful effects to the environment and human health. The present study aimed to investigate the potential toxic effects of penconazole, a triazole fungicide, on the cerebrum and cerebellum of adult rats. Penconazole was administered intraperitoneally to male Wistar rats at a dose of 67 mg kg-1 body weight every 2 days during 9 days. Results showed that penconazole induced oxidative stress in rat cerebrum and cerebellum tissues. In fact, we have found a significant increase in malondialdehyde, hydrogen peroxide, and advanced oxidation protein product levels, as well as an alteration of the antioxidant status, enzymatic (superoxide dismutase and catalase) and nonenzymatic (glutathione), the cholinergic function, and membrane-bound ATPases (Na+/K+-ATPase and Mg2+-ATPase). Penconazole also provoked histological alterations marked by pyknotic and vacuolated neurons in the cerebrum and apoptosis and edema in the cerebellum Purkinje cells' layer. Therefore, the use of this neurotoxicant fungicide must be regularly monitored in the environment.

Therapeutic efficacy of silymarin from milk thistle in reducing manganese-induced hepatic damage and apoptosis in rats.

Oxidative stress has been proposed as a possible mechanism involved in manganese (Mn) toxicity. Using natural antioxidants against metal-induced hepatotoxicity is a modern approach. The present study investigated the beneficial role of silymarin, a natural flavonoid, in Mn-induced hepatotoxicity focusing on histopathology and biochemical approaches. Male Wistar rats were exposed orally to manganese chloride (20 mg/mL) for 30 days followed by intraperitoneal cotreatment with silymarin (100 mg/kg). Exposure to Mn resulted in a significant elevation of the plasma marker enzyme activities and bilirubin level related to liver dysfunction of reactive oxygen species (ROS) production and hepatic oxidative stress indices. This metal reduced the activities of superoxide dismutase, catalase and glutathione peroxidase and nonenzymatic antioxidant levels such as reduced glutathione, total sulfhydryl groups and vitamin C. In addition, it caused hepatic hemorrhage, cellular degeneration and necrosis of hepatocytes as indicated by liver histopathology and DNA fragmentation studies. Coadministration of silymarin alleviated Mn oxidative damage effects by inhibiting ROS generation. Histological studies also supported the beneficial role of silymarin against Mn-induced hepatic damages. Combining all, results suggested that silymarin could protect hepatic tissues against Mn-induced oxidative stress probably through its antioxidant activity. Therefore, its supplementation could provide a new approach for the reduction in hepatic complication due to Mn poisoning.

Protein restriction in pregnant- and lactating rats-induced oxidative stress and hypohomocysteinaemia in their offspring.

Hyperhomocyteinaemia has been associated with pathological and stressful conditions and considered as a risk factor for cardiovascular diseases. Maternal protein restriction during late pregnancy and postnatal period is a stressful state to their offspring which is associated with disruption of various physiological processes. The objective of the current study was to evaluate the effects of maternal protein restriction during late pregnancy and early postnatal periods on systemic oxidative stress parameters and on homocysteine metabolism of their offspring. For this purpose, 12 female rats were divided into two groups: a control group (C) with free access to standard diet (20% protein) and a protein restricted group (PR) with free access to a low protein diet (7% protein) from the day 14 of pregnancy until day 14 after delivery. An increase of thiobarbituric acid-reactive substance levels (TBARS) in plasma (+40%, p < 0.01) and in liver (+37%, p < 0.001) with a concomitant decrease in the activities of catalase (CAT) and superoxide dismutase (SOD) observed in undernourished pups suggest the possibility of oxidative stress. Moreover, no significant changes in total glutathione levels (tGSH) were also observed to be associated with a significant decrease in homocysteine concentrations (-35%; p < 0.001). In their mothers, an alteration of antioxidant enzyme activities (CAT and SOD) and slight increase of TBARS levels were observed. Whereas homocysteine and tGSH levels were unchanged in comparison with those fed ad libitum. These results suggested that PR diet given to mothers during late pregnancy and early postnatal periods induced oxidative stress and hypohomocysteinaemia in their offspring.

Hypolipidemic and hepatoprotective effects of flax and pumpkin seed mixture rich in omega-3 and omega-6 fatty acids in hypercholesterolemic rats.

Flax and pumpkin seeds are a rich source of unsaturated fatty acids, antioxidants and fibers, known to have anti-atherogenic and hepatoprotective activities. These effects were evaluated in Wistar rats fed with 1% cholesterol diet. The study was performed on 30 male rats divided into three groups: a control group (CD), CD-chol group fed diet with 1% cholesterol and MS-chol group fed diet enriched with flax and pumpkin seed mixture. In CD-chol group, total cholesterol TC, triacylglycerol TG in plasma and liver, plasma LDL-C, atherogenic index AI and LDL/HDL ratio significantly increased. In MS-chol group lipid parameters decreased significantly, plasma and liver fatty acid composition showed an increase of PUFAs (ALA and LA), and MUFAs (oleic and eicosaenoic acid) and a decrease of SFA (palmitic and stearic acid). In plasma and liver of MS-chol group, malondialdehyde levels decreased and the efficiency of antioxidant defense system was improved compared to CD-chol group. Liver histological sections showed lipid storage in hepatocytes of CD-chol group and an improvement was noted in MS-chol group. Our results suggested that flax and pumpkin seed mixture had anti-atherogenic and hepatoprotective effects which were probably mediated by unsaturated fatty acids present in seed mixture.

Maternal low-protein diet affects bone mass and mineral metabolism in suckling rats.

This study was performed to analyse the effects of low-protein diet (7%) on bone mass and mineral metabolism in rat pups whose mothers were submitted to protein-restricted diet during late pregnancy and early post-natal periods. For this purpose, 12 pregnant Wistar rats were divided into two groups of six animals each: a control group with free access to standard diet (20% protein) and protein-restricted group (PR) fed with low-protein diet (7% protein) from the 14th day of pregnancy until day 14 after delivery. Body weight, femur bone mass, plasma thyroid hormones (FT(4) and FT(3)), biochemical bone marker levels [alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (ACP)] and bone DNA content were recorded. In undernourished pups, a decrease in body weight (-47%, p < 0.001) in skeletal growth (-11%, p < 0.001) and in bone DNA content (-48%, p < 0.001) were observed. Plasma protein and albumin levels and thyroid status were also decreased in undernourished rat pups compared with those of control group. The circulating amino acid levels were decreased in pups. While in their mothers, some of them were increased and the others were decreased. A positive correlation was observed between bone mass and plasma thyroid hormone levels and ALP activity and plasma protein levels, and a negative correlation with ACP activity. Plasma ALP levels were decreased by 19%, whereas plasma tartrate-resistant ACP levels were increased by 33% indicating a hyperactivity of bone remodelling. These results showed that protein-restricted diet given to mothers during late pregnancy and early post-natal periods induced changes in body weight, skeletal growth and bone metabolism in their offspring.

Dimethoate effects on thyroid function in suckling rats.

The aim of our work is to study dimethoate effects on thyroid function given in drinking water (40 mg/kg body weight, equivalent to 0.2 g/L) to mothers from day zero until the 10th day after delivery. Pups and their mothers were sacrificed on day ten after parturition. Compared to a control group, dimethoate-treated pups showed a 48% decrease in body weight which could be attributed to a defect in thyroid hormones. Indeed, after treatment by dimethoate, plasma rates of free T4 and T3 decreased by 56% and 40% in the young and by 27% and 15% in dams respectively. We can attribute the reduction in plasma thyroxine and triiodothyronine rates to a decrease in thyroid iodine levels (-75%) in the young and (-24%) in their mothers. The decrease in production of thyroid hormones after dimethoate treatment affect thyroid stimulating hormone (TSH) levels. In fact, plasma TSH levels were multiplied in dimethoate-treated group by factors of 2.31 in dams and 1.96 in their offspring. These biochemical modifications confirmed the histological thyroid aspects of pups and dams. In fact, in dimethoate-treated rats, some thyroid follicles of pups presented vesicular cavities without colloid; others contained colloid. However in dams, thyroid follicles presented cubical epithelial cells which surrounded empty vesicular cavities.

[Induction and reversibility of thyroid proliferative changes in suckling rats given thiocyanate]. / Induction et réversibilité d'action du thiocyanate sur la fonction thyroïdienne chez le rat en période d'allaitement.

Potassium thiocyanate given in the drinking water of pregnant rats led to decreased body weight in their 14-day-old offspring (27%) without altering thyroid weight. Reduction of the suckling rat's body weight could be explained be defective thyroxinemia (38). Plasma FT3 and TSH were unchanged after thiocyanate treatment. The biochemical changes were in agreement with the histological aspects of the hypothyroid animals. The typical pattern was hyperplastic goiter. Colloid volume was reduced compared with controls. Presence of resorbed peripheral vacuoles, a sign of thyroid hyperactivity, was disclosed by a three-fold increase in radioiodide (131I) uptake compared with controls. When the antithyroid drug was removed from the mother's milk, the pups'weight increased but did not reach control values. Plasma thyroid hormone levels returned to normal and even exceeded control values in spite of partial recovery of thyroid iodine content when thiocyanate treatment was stopped for ten days.

[Thiocyanate and central nervous system maturation of young mice]. / Effets du thiocyanate sur la fonction thyroïdienne et la maturation du système nerveux central de la jeune souris.

Potassium thiocyanate, given to the drink of pregnant mothers provoked a body weight decrease of 14 day-old mice (-18%), without perturbations of cerebrum and cerebellum weights. The reduction of pups' body weight could be explained by a decrease of plasmatic thyroid hormone levels: FT3 and FT4, (-54; -57%) in youngs and (-66; -49%) in their mothers. A defect of thyroid hormone levels, observed in young mice, provoked a decrease of cerebrum and cerebellum protein concentrations (-15 and -13%) respectively. Modifications of biochemical parameters confirmed the histological aspects of hypothyroid mice cerebellum with purkinje cells incompletely differentiated. When thiocyanate ion was removed from mothers' drink, we have noted in pups a partial return of some biochemical parameters (iodine thyroid contents, protein concentrations of cerebrum and cerebellum) and of cerebellum histological aspects. While thyroxinemia (FT4) and plasmatic FT3 levels were completely restored and even exceeded control values, which were necessary for central nervous system maturity of young.

[Non-pharmacologic treatment of atrial fibrillation]. / Traitement non pharmacologique de la fibrillation auriculaire.

Curative non pharmacological treatment of AF includes MAZA anti arrhythmic surgery and ist different variants which are reserved to AF associated with mitral valve disease. Radiofrequency (RF) ablation of AF creating lesions mimicking the MAZE procedure is another curative treatment but its numerous complications lead to put it in stand-by. Focal AF radiofrequency ablation is the only curative method that has encouraging results. The development of the internal cardioversion led to the development of the implantable atrial defibrillator. In spite of the low energy used, the internal shocks are often painful and not well tolerated conducting to stop the use of these devices. Prophylactic atrial pacing among patients with interatrial conduction delay is well established by dual site pacing pioneers. After several attempts to restore sinus rhythm and the fail of drug therapy to reduce heart rate, the latest solution to prevent tachycardiomyopathy is the atrio-ventricular (AV) node modulation or ablation using RF energy.

[Propythiouracil and perchlorate effects on thyroid function in young and lactating mice]. / Effets de deux antithyroïdiens de synthèse (propylthiouracile et perchlorate) sur la fonction thyroïdienne de la souris en période d'allaitement.

We have studied the effects of propythiouracil (PTU) or perchlorate (CIO(4)(-)), given to the mothers' drink from the 15(th) day of pregnancy until the day of sacrifice, on thyroid function of suckling mice. Antihyroid drugs (PTU or CIO(4)(-)) provoked growth perturbations of young mice during studied ages from 6 to 18 days. A decrease of body weight was respectively as follows: 14 and 22% in 6 day-old mice; 16 and 23% in 10 day-old mice; 18 and 18% in 14 day-old mice; 19 and 11% in 18 day-old mice. We have noticed an hypertrophy of thyroid glands of pups and their mothers caused by an increase of pituitary TSH. Thyroid follicles presented the aspect of hypothyroid animals with an increase of follicular number and vascularisation. Structural modifications confirmed biochemical results. In fact thyroid iodine contents decreased strongly in young as follow: 40 and 43% in 6 day-old mice; 51 and 50% in 10 day-old mice; 66 and 84% in 14 day-old mice; 54 and 89% at 18 day-old mice and in their mothers (50, 37%; 59, 54%; 75, 65% and 85, 72%) respectively after PTU or CIO(4)(-) treatment. A decrease of iodine thyroid gland was accompanied by an important fall of free thyroid hormones levels (FT3 and FT4) in young and adult mice. A decrease of thyroid hormonemia could explain the pups' growth perturbations.

[Analysis of iodine compounds in young rat skin in the period of suckling and in the adult. Effect of perchlorate]. / Analyse des composés iodés de la peau chez le jeune rat en période d'allaitement et chez l'adulte. Effet du perchlorate.

In the suckling and adult rats equilibrated or no by 125I, cutaneous iodine analysed by dialysis and chromatography techniques (Dowex and Sephadex) was the purpose of this study. Dialysis studies had shown that most of steady or labelled skin iodine had an iodide form (90 to 95% of the total iodine). There were at least two intracellular iodide pools: the first one was quickly dialysable, in fact about 60 percent of initial radioactivity represented the intracellular iodide equilibrated with extracellular fluid. The other one wasn't or was little dialysable representing probably the cutaneous iodide storage compartment. Chromatography studies (Dowex or Sephadex) demonstrated that the skin of the young and adult rat contained T4 and T3 hormones in a small percentage. The iodide represented a value more than 90% of initial total radioactivity. Results concerning kinetic skin iodine, eight and twenty four hours after LT4(125)I injected to adults and to control and iodine deficient ten day old rats, confirmed those obtained here by Dowex chromatography and previous ones. Triiodothyronine (T3) might have an origin either in thyroid synthesis or in deiodination of T4. Consequently we may say that the skin of the 10 day and 14 day old rats presented a great accumulation of iodide. The perchlorate inhibited this storage. Indeed, in young deficient iodine rats at birth, cutaneous iodide concentrations were reduced whereas those of T4 and T3 as well as the ratio T3/T4 haven't been modified. Therefore the iodine deficiency seemed to have a few effects on the skin deiodinating activity. Indeed the skin of iodine deficient immature rat became unable to accumulate iodide. The main effect of the skin iodine deficiency was the inhibition of iodide transport from the extracellular fluid to the intracellular one, but not inside cellular structures.

Iodide and T4 kinetics in plasma, thyroid gland and skin of 10-day-old rats: effects of iodine deficiency.

The effects of iodine deficiency on the peripheral metabolism of thyroid hormone in immature rat were evaluated by measuring the kinetics of iodide and thyroxine (T4) in control and iodine-deficient 10-day-old rats. Iodine-deficient pups were obtained by giving the mother drinking water containing perchlorate; this anion is not transferred but prevents iodine transfer in the mother's milk. Labelled iodocompounds were measured in plasma, thyroid and skin for 48 h following intravenous injection of Na131I plus [125I]T4. Data were interpreted by compartmental analysis. The iodide plasma clearance rate, plasma equivalent distribution volume, plasma concentration, production and iodine thyroid content of iodine-deficient rats were significantly lower (-29%, -31%, -84%, -89% and -87% respectively) than in control 10-day-old rats. The iodide thyroid uptake was reduced (-47%) but remained higher than the release of iodine as T4. Cutaneous iodine was lost much more quickly by iodine-deficient pups than by control pups, explaining the decreased iodide distribution volume. The parameters of T4 metabolism were not changed by iodine deficiency, except for a slight but significant reduction of the thyroxinemia and T4 pools (-13%). Thence, T4 production was not significantly changed (about 8 pmol/h in control and iodine-deficient rats). The labelled T4 curves in iodine-deficient and control skin were superimposed and the patterns of labelled T3 derived from [125I]T4 were identical. Thus, the skin of immature rats converts T4 to T3; this process was not disturbed by iodine deficiency. The thyroid function of immature rats is particularly resistant to iodine deficiency, but the mechanisms remain unknown.

Adrenal catecholamines content in fetal and newborn rats.

The adrenal epinephrine content of newborn rats delivered by caesarian section on day 21.5 of gestation and maintained at thermal neutrality (37 degrees C) did not decrease over the 6 h following birth in spite of a transient phase of hypoglycemia. Cold exposure (30 or 24 degrees C) of the newborn rats immediately after birth did not decrease their adrenal epinephrine content. A decrease in adrenal epinephrine content is observed in 21.5-day-old rat fetuses after insulin-induced hypoglycemia for 4 h, after 2-deoxy-D-glucose injection or after anoxia. In 20.5-day-old rat fetuses, insulin-induced hypoglycemia for 4 h or 2-deoxy-D-glucose did not decrease the adrenal epinephrine content of the fetus. No variation was observed in norepinephrine content of the adrenal gland in all these situations. It is concluded that spontaneously occurring hypoglycemia or cold exposure are not sufficient stimuli to induce adrenal epinephrine depletion. It is suggested that hypoxia is perhaps the physiological stimulus for epinephrine secretion in newborn rats.