Dimethoate Induces Kidney Dysfunction, Disrupts Membrane-Bound ATPases and Confers Cytotoxicity Through DNA Damage. Protective Effects of Vitamin E and Selenium

Dimethoate (DM) is an organophosphate insecticide widely used in agriculture and industry and has toxic effects on non-target organisms especially mammalian. However, we still know little about DM-induced kidney injury and its alleviation by natural antioxidants. In the present study, selenium (Se), vitamin E, DM, Se+DM, vitamin E+DM, Se+vitamin E+DM were given to adult rats for 4 weeks. Plasma creatinine and uric acid, kidney MDA, PC, H₂O₂ and AOPP levels were higher, while Na⁺-K⁺-ATPase and LDH values were lower in the DM group than those of controls. A smear without ladder formation on agarose gel was shown in the DM group, indicating random DNA degradation and DM-induced genotoxicity. A decrease in kidney GSH, NPSH and plasma urea levels and an increase in GPx, SOD and catalase activities were observed in the DM group when compared to those of controls. Plasma cystatin C levels increased, indicating a decrease in glomerular filtration rate. When Se or vitamin E was added through diet, the biochemical parameters cited above were partially restored in Se+DM and vitamin E+DM than DM group. The joint effect of Se and vitamin E was more powerful against DM-induced oxidative stress and kidney dysfunction. The changes in biochemical parameters were substantiated by histological data. In conclusion, our results indicated a possible mechanism of DM-induced nephrotoxicity, where renal genotoxicity was noted, membrane-bound ATPases and plasma biomarkers were disturbed. Se and vitamin E ameliorated the toxic effects of this pesticide in renal tissue suggesting their role as potential antioxidants.     

Oxidative stress and thyroid impairment after gibberellic acid treatment in pregnant and lactating rats and their offspring

Gibberellic acid (GA?) has been worldwide used in agriculture as a plant growth regulator. The purpose of this study is to assess the effects of GA? on the morphology and the thyroid hormone levels in adult rats and their suckling pups. Animals were given daily 200 ppm GA? in drinking water from the 14th day of pregnancy until day 14 after delivery. Compared with a control group, GA?-treated mothers and pups showed an increase in body and thyroid weights, a decrease in plasma FT? and FT? levels, which were more pronounced in pups than in their mothers. Thyroid iodine content was also decreased in pups. These biochemical modifications corresponded histologically; the majority of follicles had cubical epithelial cells, which surrounded empty vesicular cavities. Toxicity was objectified by a significant increase in plasma malondialdehyde, protein carbonyls, and advanced oxidation protein products levels in GA?-treated dams and their suckling pups; while, the activities of superoxide dismutase, catalase, and glutathione peroxidase were decreased in plasma of both dams and their pups. Moreover, a significant decline was observed in plasma glutathione, nonprotein thiols, and vitamin C levels. We conclude that GA? treatment affects thyroid function and plasma antioxidant status in adult rats and their progeny.     

Oxidative damage induced by chromium (VI) in rat erythrocytes: protective effect of selenium

Excess chromium (Cr) exposure is associated with various pathological conditions including hematological dysfunction. The generation of oxidative stress is one of the plausible mechanisms behind Cr-induced cellular deteriorations. The efficacy of selenium (Se) to combat Cr-induced oxidative damage in the erythrocytes of adult rats was investigated in the current study. Female Wistar rats were randomly divided into four groups of six each: group I served as controls which received standard diet, group II received in drinking water K₂Cr₂O₇ alone (700 ppm), group III received both K₂Cr₂O₇ and Se (0.5 Na₂SeO₃ mg/kg of diet), and group IV received Se (0.5 mg/kg of diet) for 3 weeks. Rats exposed to K₂Cr₂O₇ showed an increase of malondialdehyde and protein carbonyl levels and a decrease of sulfhydryl content, glutathione, non-protein thiol, and vitamin C levels. A decrease of enzyme activities like catalase, glutathione peroxidase, and superoxide dismutase activities was also noted. Co-administration of Se with K₂Cr₂O₇ restored the parameters cited above to near-normal values. Therefore, our investigation revealed that Se was a useful element preventing K₂Cr₂O₇-induced erythrocyte damages.     

Negatively charged self-assembling DNA/poloxamine nanospheres for in vivo gene transfer

Over the past decade, numerous nonviral cationic vectors have been synthesized. They share a high density of positive charges and efficiency for gene transfer in vitro. However, their positively charged surface causes instability in body fluids and cytotoxicity, thereby limiting their efficacy in vivo. Therefore, there is a need for developing alternative molecular structures. We have examined tetrabranched amphiphilic block copolymers consisting of four polyethyleneoxide/polypropyleneoxide blocks centered on an ethylenediamine moiety. Cryo-electron microscopy, ethidium bromide fluorescence and light and X-ray scattering experiments performed on vector–DNA complexes showed that the dense core of the nanosphere consisted of condensed DNA interacting with poloxamine molecules through electrostatic, hydrogen bonding and hydrophobic interactions, with DNA molecules also being exposed at the surface. The supramolecular organization of block copolymer/DNA nanospheres induced the formation of negatively charged particles. These particles were stable in a solution that had a physiological ionic composition and were resistant to decomplexation by heparin. The new nanostructured material, the structure of which clearly contrasted with that of lipoplexes and polyplexes, efficiently transferred reporter and therapeutic genes in skeletal and heart muscle in vivo. Negatively charged supramolecular assemblies hold promise as therapeutic gene carriers for skeletal and heart muscle-related diseases and expression of therapeutic proteins for local or systemic uses.     

Caffeine reversal of sleep deprivation effects on alertness,mood and repeated sprint performances in physical education students

The aim of this study was to evaluate the effects of caffeine ingestion and partial sleep deprivation on mood and cognitive and physical performances. In randomised order, 12 healthy male physical education students completed four test sessions at 18:00 h after placebo or 5 mg/kg of caffeine ingestion during a baseline night (RN) (bed time: from 22:00 to 07:00 h), or during a night of partial (four hrs) sleep deprivation (PSD). During each test session, participants performed a reaction time test, a vigilance test, the 10 s Wingate cycling test during (measuring peak power (PP) and anaerobic capacity), and the 5 m multiple shuttle test (measuring peak distance (PD), total distance (TD), and fatigue index (FI)). Compared to RN, simple reaction time, vigilance, PP, PD, TD, and FI were altered by PSD the following day after placebo ingestion with increased reaction time and FI and reduced PP, PD, TD, and vigilance (p < 0.001). Moreover, during PSD condition, PP, PD, and TD were significantly higher after caffeine ingestion in comparison with placebo ingestion (p < 0.05). However, both simple reaction times and vigilance were significantly lower after caffeine ingestion in comparison with placebo during PSD (p < 0.05). Caffeine is an effective strategy to maintain physical and cognitive performances the day after PSD.     

Evaluation of some biological parameters of Opuntia ficus indica. 2. Influence of seed supplemented diet on rats

The present research was undertaken to evaluate some biological parameters in rats fed with a supplemented diet with Opuntia ficus indica powder seeds. Feed intake and body weight of rats were measured every two days during nine weeks of treatment. Digestibility, feed conversion efficiency and protein efficiency ratio were determined. No difference in digestibility was noticed between the different diets. The results indicated a significant decrease in body weight of rats receiving a diet partially substituted with O. ficus indica powder seeds, probably due to a significant decrease in serum-free thyroxin (FT(4)) compared to the control group. In the treated group, a decrease of glucose concentration in blood and an increase of glycogen in liver and skeletal muscle were noticed. A significant increase in HDL-cholesterol was noted in the group receiving the supplemented diet with O. ficus indica powder seeds. These results suggest that O. ficus indica seeds can be used as a healthy food.     

Manganese induces oxidative stress, redox state unbalance and disrupts membrane bound ATPases on murine neuroblastoma cells in vitro: protective role of silymarin

Manganese (Mn) is an essential trace element required for ubiquitous enzymatic reactions. Chronic overexposure to this metal may promote potent neurotoxic effects. The mechanism of Mn toxicity is not well established, but several studies indicate that oxidative stress play major roles in the Mn-induced neurodegenerative processes. Silymarin (SIL) has antioxidant properties and stabilizes intracellular antioxidant defense systems. The aim of this study was to evaluate the toxic effects of MnCl₂ on the mouse neuroblastoma cell lines (Neuro-2A), to characterize the toxic mechanism associated with Mn exposure and to investigate whether SIL could efficiently protect against neurotoxicity induced by Mn. A significant increase in LDH release activity was observed in Neuro-2A cells associated with a significant decrease in cellular viability upon 24 h exposure to MnCl₂ at concentrations of 200 and 800 μM (P < 0.05) when compared with control unexposed cells. In addition, exposure cells to MnCl₂ (200 and 800 μM), increases oxidant biomarkers and alters enzymatic and non enzymatic antioxidant systems. SIL treatment significantly reduced the levels of LDH, nitric oxide, reactive oxygen species and the oxidants/antioxidants balance in Neuro-2A cells as compared to Mn-exposed cells. These results suggested that silymarin is a powerful antioxidant through a mechanism related to its antioxidant activity, able to interfere with radical-mediated cell death. SIL may be useful in diseases known to be aggravated by reactive oxygen species and in the development of novel treatments for neurodegenerative disorders such as Alzheimer or Parkinson diseases.     

Plasma Leptin and Acute Serotoninergic Stimulation of the Corticotropic Axis in Women Who Are Normal Weight or Obese

OPPERT, JEAN-MICHEL, NAJIBA LAHLOU, BLANDINE LAFERRÈRE, MARC ROGER, ARNAUD BASDEVANT, BERNARD GUY-GRAND. Plasma leptin and acute serotoninergic stimulation of the corticotropic axis in women who are normal weight or obese. In some recent studies, glucocorticoid treatment was associated with rapid induction of obese (ob) gene expression in adipose tissue of normal rats and in isolated adipocytes. We studied the effect of acute stimulation of the corticotropic axis on plasma leptin, the ob gene product, in 7 women of normal weight and 12 women with obesity. Under double-blind, placebo-controlled conditions, a single 12.5-mg dose of clomipramine, a serotonin uptake inhibitor, was administered intravenously in 15 minutes. Mean basal plasma leptin was increased more than 3-fold in subjects with obesity compared with subjects of normal weight (35.1 ± 4.9 ng/mL vs. 8.9 ± 1.4 ng/mL, p=0.001). Whereas corticotropin (ACTH) and Cortisol responses were increased in women who were obese compared with women who were lean, no significant effect of clomipramine infusion was found on plasma leptin concentrations measured during the following 150 minutes in both groups. There was a strong positive correlation between basal plasma leptin concentrations and body mass index (r=0.92, p<0.0001). In six subjects with obesity studied after a moderate weight loss, mean basal plasma leptin was significantly decreased (43.7 ± 6.4 ng/mL before vs. 28.0 ± 8.1 ng/mL after, p=0.04), but the hormonal response pattern to clomipramine administration was unchanged. We conclude that, at least in the short term, an acute stimulation of the corticotropic axis does not seem to increase leptin secretion in humans, as shown by the response to the serotoninergic agent clomipramine.     

Food restriction induced thyroid changes and their reversal after refeeding in female rats and their pups

In the present study, two groups of pregnant female rats were submitted to food restriction (24 h fast versus 24 h diet intake) from the 14th day of pregnancy until either the 14th day (group B) or the 4th day after parturition (group C). All pups and their mothers were sacrificed on day 14 after delivery. The body weight of the 14-day-old pups (group B) was 46% less than the controls (group A). Free thyroxine and free triiodothyronine levels in the plasma were reduced by 44 and 16% in pups and by 20 and 36% in their mothers, respectively. These reductions were correlated with a decrease in thyroid iodine content of the pups (-50%) and their mothers (-24%). Radioiodine uptake (131I) by the thyroid gland of pups was significantly increased by 27%. Plasma TSH levels were decreased by 38% in pups and by 44% in dams. Morphological changes in thyroid glands were observed in energy restricted dams and in their pups. Some of follicles in pups were empty. Moroever in dams, we noted the presence of peripheral resorbed vacuoles, sign of thyroid hyperactivity. After a refeeding (group C) period of ten days, total recovery occurred in plasma thyroid hormone levels (FT4 and FT3) and in thyroid iodine contents of pups in spite of a partial recovery of body weights and plasma TSH levels. In dams, a partial recovery occurred in plasma thyroid hormone levels in spite of total recovery in thyroid iodine contents, while plasma TSH levels exceeded control values. A significant amelioration in thyroid histological aspects was observed in pups and their dams.     

Silymarin, a natural antioxidant, protects cerebral cortex against manganese-induced neurotoxicity in adult rats

Manganese (Mn) is an essential element for biological systems, nevertheless occupational exposure to high levels of Mn can lead to neurodegenerative disorders, characterized by serious oxidative and neurotoxic effects with similarities to Parkinson’s disease. The aim of this study was to investigate the potential effects of silymarin (SIL), an antioxidant flavonoid, against manganese chloride induced neurotoxicity both in vivo (cerebral cortex of rats) and in vitro (Neuro2a cells). Twenty-eight male Wistar rats were randomly divided into four groups: the first group (C) received vehicle solution (i.p.) served as controls. The second group (Mn) received orally manganese chloride (20 mg/ml). The third group (Mn + SIL) received both Mn and SIL. The fourth group (SIL) received only SIL (100 mg/kg/day, i.p.). Animals exposed to Manganese chloride showed a significant increase in TBARS, NO, AOPP and PCO levels in cerebral cortex. These changes were accompanied by a decrease of enzymatic (SOD, CAT, GPx) and non-enzymatic (GSH, NpSH, Vit C) antioxidants. Co-administration of silymarin to Mn-treated rats significantly improved antioxidant enzyme activities and attenuated oxidative damages observed in brain tissue. The potential effect of SIL to prevent Mn induced neurotoxicity was also reflected by the microscopic study, indicative of its neuroprotective effects. We concluded that silymarin possesses neuroprotective potential, thus validating its use in alleviating manganese-induced neurodegenerative effects.