Response of lead-induced oxidative stress and alterations in biogenic amines in different rat brain regions to combined administration of DMSA and MiADMSA

The present study was planned to investigate if combined administration of meso-2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) could achieve better recovery in the altered biochemical parameters suggestive of brain oxidative stress and depletion of lead from blood and brain following acute lead exposure. Male Wistar rats were exposed to lead nitrate (50 mg/kg, i.p., once daily for 5 days) followed by treatment with the above chelating agents using two different doses of 25 or 50 mg/kg (orally) either alone and in combination once daily for five consecutive days. Lead exposure resulted in the significant inhibition of δ-aminolevulinic acid dehydratase activity and depletion of glutathione (GSH) in blood. These changes were accompanied by significant reduction in blood hemoglobin, RBC levels and superoxide dismutase and catalase activities. Significant increase in blood reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) levels were noted. We observed marked increase in brain ROS level while GSH/oxidized glutathione ratio showed significant decrease accompanied by a significant increase in blood and brain lead concentration. The levels of norepinephrine, dopamine and serotonin in different brain regions were also altered on lead exposure. Co-administration of DMSA and MiADMSA particularly at the lower dose was most effective in the recovery of lead-induced changes in the hematological variables and oxidative stress and resulted in more pronounced depletion of lead from blood and brain compared to monotherapy with these chelators. On the other hand, combined administration of MiADMSA (50 mg/kg) in combination with DMSA (25 mg/kg each) had additional beneficial effect over the individual effect of chelating agent in the recovery of altered levels of brain biogenic amines. The study suggests that administration of MiADMSA is generally a better lead chelator than DMSA while combined administration of DMSA and MiADMSA might be a better treatment option compared to monotherapy at least in the removal of lead from the target tissues.     

Aluminum-induced oxidative stress in rat brain: response to combined administration of citric acid and HEDTA

Aluminum, a known neurotoxic substance, has been suggested as a contributing factor in the pathogenesis of Alzheimer's disease. Therapeutic efficacy of combined administration of citric acid (CA) and N-(2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA) was evaluated in decreasing blood and brain aluminum concentration and parameters indicative of hematological disorders and brain oxidative stress. Adult male wistar rats were exposed to drinking water containing 0.2% aluminum nitrate for 8 months and treated once daily for 5 consecutive days with CA (50 mg/kg, orally) or HEDTA (50 mg/kg, intraperitoneally) either individually or in combination. Aluminum exposure significantly inhibited blood delta-aminolevulinic acid dehydratase while increased zinc protoporphyrin confirming changed heme biosynthesis. Significant decrease in the level of glutathione S-transferase in various brain regions and an increase in whole brain thiobarbituric acid reactive substance, and oxidized glutathione (GSSG) levels were also observed. Glutathione peroxidase activity showed a significant increase in cerebellum of aluminum exposed rats. Most of the above parameters responded moderately to the individual treatment with CA and HEDTA, but significantly reduced blood and brain aluminum burden. However, more pronounced beneficial effects on some of the above described parameters were observed when CA and HEDTA were administered concomitantly. Blood and brain aluminum concentration however, showed no further decline on combined treatment over the individual effect with HEDTA or CA. We conclude that in order to achieve an optimum effect of chelation, combined administration of CA and HEDTA might be preferred. However, further work is needed before a final recommendation could be made.     

Differential effects of short-term lindane administration on parameters related to oxidative stress in rat liver and erythrocytes

Parameters related to oxidative stress in rat liver and erythrocytes were studied after short-term administration (60 and 90 days) of 1000 ppm of lindane in the diet. Lindane induced an oxidative stress condition in the liver, which is related to an enhancement in microsomal NADPH-cyto-chrome c reductase and NADPH oxidase activities, superoxide radical formation and cytochrome P450 content, produced independently of the time of treatment. Also, decreased activities of glutathione peroxidase and catalase were concomitantly observed. Although these changes were paralleled by an increase in lipid peroxidation indices, such as production of thiobarbituric acid reactants and spontaneous chemiluminescence, no evidence of liver injury was obtained. Lindane treatment did not exert quantitatively important changes in the pro-oxidant/anti-oxidant status of the erythrocyte, with reduction in the red blood cell mass possibly reflecting actions of the insecticide on the eryth-ropoietic process.     

Metal chelator combined with permeability enhancer ameliorates oxidative stress-associated neurodegeneration in rat eyes with elevated intraocular pressure

Because as many as half of glaucoma patients on intraocular pressure (IOP)-lowering therapy continue to experience optic nerve toxicity, it is imperative to find other effective therapies. Iron and calcium ions play key roles in oxidative stress, a hallmark of glaucoma. Therefore, we tested metal chelation by means of ethylenediaminetetraacetic acid (EDTA) combined with the permeability enhancer methylsulfonylmethane (MSM) applied topically on the eye to determine if this noninvasive treatment is neuroprotective in rat optic nerve and retinal ganglion cells exposed to oxidative stress induced by elevated IOP. Hyaluronic acid (HA) was injected into the anterior chamber of the rat eye to elevate the IOP. EDTA–MSM was applied topically to the eye for 3 months. Eyeballs and optic nerves were processed for histological assessment of cytoarchitecture. Protein–lipid aldehyde adducts and cyclooxygenase-2 (COX-2) were detected immunohistochemically. HA administration increased IOP and associated oxidative stress and inflammation. Elevated IOP was not affected by EDTA–MSM treatment. However, oxidative damage and inflammation were ameliorated as reflected by a decrease in formation of protein–lipid aldehyde adducts and COX-2 expression, respectively. Furthermore, EDTA–MSM treatment increased retinal ganglion cell survival and decreased demyelination of optic nerve compared with untreated eyes. Chelation treatment with EDTA–MSM ameliorates sequelae of IOP-induced toxicity without affecting IOP. Because most current therapies aim at reducing IOP and damage occurs even in the absence of elevated IOP, EDTA–MSM has the potential to work in conjunction with pressure-reducing therapies to alleviate damage to the optic nerve and retinal ganglion cells.     

The antioxidant effect of Aronia melanocarpa extract in rats oxidative stress induced by cisplatin administration

BackgroundThe reactive oxygen species generated by numerous xenobiotic substances has as consequences the impairment of different organs normal function. Many plants pose antioxidant activity to counteract oxidative stress, among them being the chokeberry (Aronia melanocarpa). The purpose of present study was to determine if the use of A. melanocarpa extract can counteract the oxidative stress induced by cisplatin administration in rats.Material and methodsThe study was made on forty Wistar rats divided in four groups as follows: C (control): receiving i.p. 1 mL of saline solution; E1: receiving cisplatin 20 mg/kg bw, i.p.; E2: receiving cisplatin 20 mg/kg bw, i.p and A. melanocarpa berry 6 % aqueous extract as drinking water, and CB (control blank): i.p 1 mL saline solution and A. melanocarpa 6 % aqueous extract for four weeks. Results. Administration of Cisplatin was followed by the increase of serum superoxide dismutase (+21.18 %, P < 0.05), catalase (+25.44 %, P < 0.001), glutathione peroxidase (+17.88 %, P < 0.05) and thiobarbituric reactive substances (+28.17 %, P < 0.01) but significantly decreased glutathione reductase (−22.35 %, P < 0.001) level comparative to control, pointing out that administration of cisplatin induced oxidative stress in rats. In groups that received A. melanocarpa extract as drinking water, we noted that the levels of the oxidative stress biomarkers tended to be restored almost to normal levels, which could be a possible good antioxidant used in condition to cisplatin use. Also, we noted a significant (P < 0.001) decrease of total antioxidant capacity in liver and kidney of rats exposed to cisplatin, recovered in those that received chokeberry. Studied trace elements important for the stress oxidative enzymes (Cu, Zn, Fe and Mn) were decreased in cisplatin exposed groups compared to control and mainly all were almost to normal level in groups receiving A. melanocarpa. Conclusion. A. melanocarpa extract due to its antioxidants content could offer protection against free radicals produced as a consequence of cisplatin use.     

Effects of beta-carotene on oxidative stress in normal and diabetic rats

Increasing interest in the role of oxidative stress and beta-carotene in disease and prevention led us to examine the results of beta-carotene's administration in diabetic rats, a model for high-oxidative stress. In this experiment, amounts of lipid peroxidation, glutathione, and glutathione disulfide, and activity levels of catalase, glutathione peroxidase, glutathione reductase, superoxide dismutase, and gamma-glutamyl transpeptidase were measured in the liver, kidney, and heart of Sprague-Dawley rats with streptozotocin-induced diabetes, and after treatment with 10 mg/kg/day of beta-carotene for 14 days. Beta-carotene treatment resulted in the reversal of the diabetes-induced increase in hepatic and cardiac catalase activity, the decreased levels of glutathione disulfide in the heart, and the increased cardiac and renal levels of lipid peroxidation. Treatment with beta-carotene exacerbated the increased glutathione peroxidase activity in the heart and the decreased catalase activity in the kidneys. In contrast to reduced hepatic glutathione levels in untreated diabetic rats, beta-carotene treatment increased glutathione levels in diabetic rats. Increased hepatic gamma-glutamyl transpeptidase activity in diabetic rats was not reduced by treatment. Thus, beta-carotene therapy for 14 days prevented/reversed some, but not all, diabetes-induced changes in oxidative stress parameters.     

The role of oxidative stress in alterations of hematological parameters and inflammatory markers induced by early hypercholesterolemia

Aims

The investigation of the effects of a high cholesterol diet (HD) for a short-time period on hematological parameters and the potential role of oxidative stress and inflammation markers.

Main methods

Rabbits were fed either a control diet or a diet containing 1% cholesterol (HD) for 5–6 weeks. The plasma lipid levels, C reactive protein (CRP), total red blood cells (RBC), total white blood cells (WBC), platelet count, packed cell volume (PCV) and leukocyte formula were determined. Oxidative stress was evaluated by the thiobarbituric acid reactive substances (TBARS), total glutathione and GSH serum level measurements. The osmotic fragility and the membrane fluidity of erythrocytes were determined. The levels of total cholesterol and TBARS were also measured in the erythrocyte membrane suspension.

Key findings

A decrease in the RBC and PCV was observed in rabbits fed on HD. The membrane rigidity and osmotic fragility were increased, and the morphological changes caused by the HD and TBARS levels in the erythrocyte membrane may account for this phenomenon. The inflammatory markers as the CRP levels, the platelet count, the WBC and the neutrophils were increased. The TBARS and GSH levels in the serum were increased and decreased, respectively.

Significance

This study shows that feeding rabbits an HD for a short time induces hematological alterations, disturbances in the oxidant–antioxidant balance and an increase of inflammatory markers. These findings support the importance of the early correction or prevention of high cholesterol levels to disrupt the process leading to the development of cardiovascular diseases.     

Short-term exposure to nonylphenol induces pancreatic oxidative stress and alters liver glucose metabolism in adult female rats

Nonylphenol is known to have estrogenic properties and has been reported to cause health hazards to animals and humans. The effects of nonylphenol on pancreas are not clearly elucidated. In this study, we sought to evaluate the effects of nonylphenol on the oxidative status of pancreas and consequential effects of nonylphenol on some of the end points of carbohydrate metabolism in the female rats. Rats were administered nonylphenol orally at the doses of 1.5, 15, and 150 mg/kg of body weight per day for 7 days. After 24 h of last dosing, the animals were sacrificed by cervical dislocation. The activities of pancreatic superoxide dismutase and catalase were significantly decreased with a concomitant increase in the levels of H2O2 and lipid peroxidation. Nonylphenol increased plasma insulin levels with a concomitant decrease in the levels of plasma glucose as compared to the control groups of rats. A dose-dependent increase in the activities of liver hexokinase and phosphofructokinase was recorded along with decreased activity of glycogen phosphorylase in liver. Western blot analysis revealed a significant decrease in the levels of GLUT-2. These results show that nonylphenol causes oxidative stress in pancreas and impairs liver glucose homeostasis.     

Chemopreventive activity of glycyrrhizin on lead acetate mediated hepatic oxidative stress and its hyperproliferative activity in Wistar rats

Lead is a pervasive environmental pollutant with no beneficial biological role and its toxicity continues to be a major health problem due to its interference with natural environment. In the present study we have evaluated the chemopreventive effect of glycyrrhizin on lead acetate mediated hepatic oxidative stress, toxicity and tumor promotion related alterations in rats. Lead acetate (100mg/kg bwt., i.p.) enhanced lipid peroxidation with concomitant reduction in glutathione, glutathione reductase, glutathione-S-transferase and glutathione peroxidase activities. There was an increase in the levels of transaminase enzymes and LDH. Lead acetate treatment also enhanced ornithine decarboxylase (ODC) activity and [(3)H] thymidine incorporation into hepatic DNA. Pretreatment of rats orally with glycyrrhizin (150 and 300 mg/kg bwt., orally) resulted in a significant decrease in hepatic microsomal lipid peroxidation (P<0.001) and increase in the level of GSH content (P<0.001) and its dependent enzyme. There was significant reduction in the levels of SGPT, SGOT and LDH (P<0.001). A significant inhibition in ODC activity and DNA synthesis (P<0.001) was also observed. On the basis of the above results it can be hypothesized that glycyrrhizin is a potent chemopreventive compound against lead acetate mediated hepatic oxidative stress, toxicity and tumor promotion related responses in rats.     

Evaluation of comparative effect of pre‐ and posttreatment of selenium on mercury‐induced oxidative stress,histological alterations,and metallothionein mRNA expression in rats

To evaluate the effect of pre‐ or posttreatment of selenium (6 μmol/kg b.w., single intraperitoneal injection) in mercury intoxication, rats were exposed to mercury (12 μmol/kg b.w., single intraperitoneal injection). Exposure to mercury resulted in induced oxidative stress in liver, kidney, and brain tissues. Marked changes in serum biochemical parameters together with alterations in histopathology and an induction in metallothionein‐I and metallothionein‐II mRNA expression in the liver and kidney were observed. Pretreatment with selenium to mercury‐exposed animals had protective effect on the liver, whereas posttreatment had partial protection on restoration of altered oxidative stress parameters. In the kidney, pretreatment with selenium showed partial protection on restoration of altered biochemical parameters, whereas no protection was observed in posttreatment. The pretreatment with selenium resulted in restoration of mercury‐induced metallothionein‐I and metallothionein‐II mRNA expression, which was completely restored in the liver whereas partial restoration was observed in the kidney. Posttreatment with selenium resulted in further induction in metallothionein‐I and metallothionein‐II mRNA expression in the liver and kidney. In the brain, selenium showed partial protection on alerted biochemical parameters. Results indicate that pretreatment with selenium is beneficial in comparison to posttreatment in mercury intoxication. Thus, dietary intake of selenium within safe limit may, therefore, enable us in combating any foreseen effects due to mercury exposure. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:123–135, 2010; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20320     

Nitric oxide and oxidative stress in brain and heart of normal rats treated with doxorubicin: role of aminoguanidine

Doxorubicin (DOX) is a potent antitumor antibiotic drug known to cause severe cardiac toxicity. Moreover, its adverse effects were found to be extended to the cerebral tissue. Several mechanisms for this toxicity have been ascribed. Currently, one of the most accepted mechanisms is through free radicals; however, the exact role of nitric oxide (NO) is still unclear. Accordingly, a NO-synthase inhibitor with some antioxidant property, aminoguanidine (AG), was selected to examine its potential protective effect against DOX-induced toxicity. Male Wistar albino rats (150-200 g) were allocated into a normal control group, DOX-induced toxicity group, and DOX + AG-treated group. DOX was injected i.p. at a dose of 10 mg/kg divided into four equal injections over a period of 2 weeks. AG was injected i.p. at a dose of 100 mg/kg 1 h before each DOX injection. The animals were sacrificed 24 h after the last DOX injection and the following parameters were measured: serum lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) activities, cardiac and cerebral contents of malondialdehyde (MDA), conjugated diene (CD), glutathione (GSH), NO, and cytosolic calcium, as well as superoxide dismutase (SOD) and glutathione peroxidase (GSHP(X)) activities. Cardiotoxicity was manifested by a marked increase in serum LDH and CPK in addition to the sharp increase in MDA reaching eightfolds the basal level. This was accompanied by significant increase in CD, NO, cytosolic calcium, SOD, and GSHP(X) content/activity by 69, 85, 76, 125, and 41% respectively as compared to normal control. On the other hand, GSH was significantly depressed. In brain, only significant increase in MDA and GSHP(X) and decrease in GSH were obtained but to a lesser extent than the cardiac tissue. AG treatment failed to prevent the excessive release of cardiac enzymes; however, it alleviated the adverse effects of DOX in heart. AG administration resulted in marked decrease in the elevated levels of MDA, NO, SOD, and GSHP(X), however, MDA level was still pathological. The altered parameters in brain were restored by AG. It is concluded that, AG could not provide complete protection against DOX-induced toxicity. Therefore, it is recommended that, maintenance of the endogenous antioxidant, GSH, and regulation of calcium homeostasis must be considered, rather than NO formation, to guard against DOX-induced toxicity.     

Effects of isoeugenol on oxidative stress pathways in normal and streptozotocin-induced diabetic rats.

Because some complications of diabetes mellitus may result from oxidative damage, we investigated the effects of subacute treatment (10mg/kg/day, intraperitoneal [ip], for 14 days) with the antioxidant isoeugenol on the oxidant defense system in normal and 30-day streptozotocin-induced diabetic Sprague-Dawley rats. Liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione content, and activities of the free radical-detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Treatment with isoeugenol reversed diabetic effects on hepatic glutathione peroxidase activity and on oxidized glutathione concentration in brain. Treatment with the lipophilic compound isoeugenol also decreased lipid peroxidation in both liver and heart of normal animals and decreased hepatic oxidized glutathione content in both normal and diabetic rats. Some effects of isoeugenol treatment, such as decreased activity of hepatic superoxide dismutase and glutathione reductase in diabetic rats, were unrelated to the oxidative effects of diabetes. In heart of diabetic animals, isoeugenol treatment resulted in an exacerbation of already elevated activities of catalase. These results indicate that isoeugenol therapy may not reverse diabetic oxidative stress in an overall sense.     

Roles of bioavailable iron and calcium in coal dust-induced oxidative stress: possible implications in coal workers' lung disease

Marked regional differences in prevalence of pneumoconiosis are apparent in the US despite comparable dust exposure. In the present study, we examined the ability of 28 coal samples to release bioavailable iron (BAI) and calcium, as well as other metals such as Cr, Ni, Cu, and Co, from three coalmine regions in Utah (UT), West Virginia (WV), and Pennsylvania (PA), respectively. BAI is defined as iron (both Fe 2+ and Fe 3+ ) released by the coals in 10 mM phosphate solution, pH 4.5, which mimics conditions of the phagolysosomes in cells. We found that coals from the UT, WV, and PA regions released average levels of BAI of 9.6, 4658.8, and 12149 parts per million (ppm, w/w), respectively, which correlated well with the prevalence of pneumoconiosis from that region (correlation coefficient r =0.92 ). The low levels of BAI in the UT coals were due to the presence of calcite (CaCO 3 ), which was shown to be preferentially acid solubilized before iron compounds. Release of iron by two coal samples from the PA and UT regions was further examined in vitro in human lung epithelial A549 cells. We found that the coal from PA, with a high prevalence of pneumoconiosis, released BAI in a dose-dependent manner, both in tissue culture media and in A549 cells. At 2 μg/cm 2 , levels of lipid peroxidation induced by the PA coal were increased 112% over control cells at 24 h treatment, and were sustained at this level for 3 days. The coal from UT, with a low prevalence of pneumoconiosis, induced a marginal increase in cellular iron at 5 and 10 μg/cm 2 treatments and had no effect on lipid peroxidation. Calcium levels in the cells treated with the PA and UT coals were 8.6 and 11.5 μmoles/10 6 cells, respectively, and were significantly higher than that in the controls (53 μmoles/10 6 cells). Our results suggest that the differences in the BAI content in the coals may be responsible for the observed regional differences in the prevalence of pneumoconiosis. Therefore, BAI may be a useful characteristic of coal for predicting coal's toxicity.     

Reactive oxygen species and mitochondrial sensitivity to oxidative stress determine induction of cancer cell death by p21

p21(Waf1/Cip1/Sdi1) is a cyclin-dependent kinase inhibitor that mediates cell cycle arrest. Prolonged p21 up-regulation induces a senescent phenotype in normal and cancer cells, accompanied by an increase in intracellular reactive oxygen species (ROS). However, it has been shown recently that p21 expression can also lead to cell death in certain models. The mechanisms involved in this process are not fully understood. Here, we describe an induction of apoptosis by p21 in sarcoma cell lines that is p53-independent and can be ameliorated with antioxidants. Similar levels of p21 and ROS caused senescence in the absence of significant death in other cancer cell lines, suggesting a cell-specific response. We also found that cells undergoing p21-dependent cell death had higher sensitivity to oxidants and a specific pattern of mitochondrial polarization changes. Consistent with this, apoptosis could be blocked with targeted expression of catalase in the mitochondria of these cells. We propose that the balance between cancer cell death and arrest after p21 up-regulation depends on the specific effects of p21-induced ROS on the mitochondria. This suggests that selective up-regulation of p21 in cancer cells could be a successful therapeutic intervention for sarcomas and tumors with lower resistance to mitochondrial oxidative damage, regardless of p53 status.     

Effects of combined quercetin and coenzyme Q(10) treatment on oxidative stress in normal and diabetic rats

Reactive oxygen species may be actively involved in the genesis of various pathological states such as ischemia-reperfusion injury, cancer, and diabetes. Our objective was to determine if subacute treatment with combined antioxidants quercetin and coenzyme Q(10) (10 mg/kg/day ip for 14 days) affects the activities of antioxidant enzymes in normal and 30-day streptozotocin-induced diabetic Sprague-Dawley rats. Quercetin treatment raised blood glucose concentrations in normal and diabetic rats, whereas treatment with coenzyme Q(10) did not. Liver, kidney, heart, and brain tissues were excised and the activities of catalase, glutathione reductase, glutathione peroxidase, superoxide dismutase, and concentrations of oxidized and reduced glutathione were determined. In the liver of diabetic rats, superoxide dismutase, glutathione peroxidase, and levels of both oxidized and reduced glutathione were significantly decreased from the nondiabetic control, and these effects were not reversed when antioxidants were administered. In kidney, glutathione peroxidase activity was significantly elevated in the diabetic rats as compared to nondiabetic rats, and antioxidant treatment did not return the enzyme activity to nondiabetic levels. In heart, catalase activity was increased in diabetic animals and restored to normal levels after combined treatment with quercetin and coenzyme Q(10). Cardiac superoxide dismutase was lower than normal in quercetin- and quercetin + coenzyme Q(10)-treated diabetic rats. There were no adverse effects on oxidative stress markers after treatment with quercetin or coenzyme Q(10) singly or in combination. In spite of the elevation of glucose, quercetin may be effective in reversing some effects of diabetes, but the combination of quercetin + coenzyme Q(10) did not increase effectiveness in reversing effects of diabetes.     

Alterations in neuromuscular junctions and oxidative stress of the soleus muscle of obese Wistar rats caused by vibratory platform training

Objectives:evaluate the effects that whole-body vibration (WBV) causes on the neuromuscular junctions and oxidative stress of the soleus muscle of obese Wistar rats.Methods:32 male Wistar rats were used, 16 of which were obesity induced by monosodium glutamate, randomized into four groups: control (GC), control with WBV (GCP), obese (GO) and obese with WBV (GOP). At the 70 days old, the training on WBV was started, performed 3 times a week, during 8 consecutive weeks. At the 130 days old, the animals were euthanized and the soleus muscles were collected.Results:Regarding the analysis of the neuromuscular junctions, the obese groups had lower mean size when compared to the control groups. On the other hand, the WBV presented higher averages when compared to the groups that did not perform the training. Regarding the oxidative stress, for the lipid peroxidation there was a significant difference between obese and non-obese animals, however, there was no difference between the animals WBV and those who did not.Conclusion:WBV promotes beneficial changes such as increased measurements of the structures of the neuromuscular junctions, but is not able to promote changes in the concentration of the cholinesterase enzyme in the synaptic cleft.     

Establishment of drug delivery system nanocapsulated with an antioxidant (+)-catechin hydrate and sodium meta borate chelator against sodium fluoride induced oxidative stress in rats

Oxidative stress a major cause of fluoride induced toxicity and mitochondrial impairment in common in experimental rats during chronic exposure of fluoride. Attempts have been made in the present experiment to diminish oxidative damage, combined therapy with (+)-catechin hydrate (an antioxidant) and sodium meta borate (chelator) were used. Fluoride intoxication in rats was performed by using 13 mg/kg NaF and both antioxidant CH and chelator SMB were used at a concentration of 8.98 μM/kg body weight. Mixture of CH and SMB in free or in PLGA nanocapsule encapsulated form were prepared. The efficacies of those formulations were tested in combating free radical mediated oxidative insult produced by sodium fluoride (NaF). The amalgamated therapy used in this experiment was shown to reduce fluoride levels in liver, brain and kidney from 9.5, 5.5, 6.3 μg/g to 4.6, 2, 2.6 μg/g, respectively. Our result indicated that the combined chelator and antioxidant therapy in nanocapsulated drug delivery system could provide a projection in combating fluoride induced mitochondrial impairment in rat model.