Do Nanoparticles of Calcium Disodium EDTA Minimize the Toxic Effects of Cadmium in Female Rats?

The present study aims to investigate the ability of CaNa2EDTA (ethylenediaminetetraacetic acid) macroparticles and nanoparticles to treat cadmium-induced toxicity in female rats and to compare their efficacies. Forty rats were divided into 4 equal groups: control, cadmium, cadmium + CaNa2EDTA macroparticles and Cd + CaNa2EDTA nanoparticles. Cadmium was added to the drinking water in a concentration of 30 ppm for 10 weeks. CaNa2EDTA macroparticles and nanoparticles (50 mg/kg) were intraperitoneally injected during the last 4 weeks of the exposure period. Every two weeks, blood and urine samples were collected for determination of urea, creatinine, metallothionein and cadmium concentrations. At the end of the experiment, the skeleton of rats was examined by X-ray and tissue samples from the kidney and femur bone were collected and subjected to histopathological examination. Exposure to cadmium increased the concentrations of urea and creatinine in the serum and the concentrations of metallothionein and cadmium in serum and urine of rats. A decrease in bone mineralization by X-ray examination in addition to various histopathological alterations in the kidney and femur bone of Cd-intoxicated rats were also observed. Treatment with both CaNa2EDTA macroparticles and nanoparticles ameliorated the toxic effects induced by cadmium on the kidney and bone. However, CaNa2EDTA nanoparticles showed a superior efficacy compared to the macroparticles and therefore can be used as an effective chelating antidote for treatment of cadmium toxicity.

Promoted inhibition of TLR4/miR-155/ NFkB p65 signaling by cannabinoid receptor 2 agonist (AM1241), aborts inflammation and progress of hepatic fibrosis induced by thioacetamide.

The endocannabinoid system plays a pivotal role, whether it is promoting or dampening hepatic fibrosis. This study investigated the role of Cannabinoid receptor 2 (CB2) activation by the synthetic analog (AM1241) on revoking the progress of liver fibrosis. Thioacetamide (TAA) was used to induce liver fibrosis in rats for three weeks followed by its concurrent administration with AM1241 at two different doses for another three weeks. Markers for liver function and oxidative stress, hepatic TNF-α, IL-1ß and IL-6, qRT-PCR expression of Toll like receptor 4 (TLR4), TGF-ß1, α-SMA and microRNA-155 (miR-155) genes, Western blot for protein levels of Vimentin and E-cadherin, immunohistochemical expression of NFκB p65 and histopathology of liver tissue were all investigated. AM1241 administration significantly maintained liver function markers and decreased; malondialdehyde, Vimentin, TLR4, TGF-ß1, α-SMA and miR-155 genes expression, NFκB p65 immune-expression and pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6). Additionally, AM1241 significantly increased E-Cadherin level, GSH and SOD content. Histologically, AM1241 limited fibroplasia extension, and broke the itinerary of bridging fibrosis. In conclusion, activation of the CB2 receptors by AM1241 promoted liver regeneration and overrun the progression of liver fibrosis through; inhibition of TLR4/miR-155/NFκB p65 pathway, suppression of pro-inflammatory IL-6, IL-1ß and TNF-α, reducing TGF-ß1, α-SMA, Vimentin and up-regulating E-Cadherin.

Nanoparticles of zinc oxide defeat chlorpyrifos-induced immunotoxic effects and histopathological alterations.

BACKGROUND AND AIM: Chlorpyrifos (CPF) is a widely used organophosphate insecticide. Nanoparticles of zinc oxide (ZnO NPs) physically showed effective adsorbing property for some insecticides. The study was conducted to estimate the potential effect of ZnO NPs against CPF toxicity. MATERIALS AND METHODS: Four groups of male rats were used; control group and three groups received drinking water contained 75 mg/L CPF, combined 75 mg/L CPF and 200 mg/L ZnO NPs, and 200 mg/L ZnO NPs, respectively. RESULTS: CPF significantly decreased macrophage activity, serum lysozyme activity, and levels of interleukin-2 (IL-2) and IL-6; increased the percentage of DNA degeneration on comet assay of lymphocytes and significantly elevated hepatic and splenic malondialdehyde contents; and decreased their glutathione contents. The liver and spleen showed marked histological alterations after exposure to CPF with decreased expression of acetylcholinesterase. The coadministration of ZnO NPs ameliorated most of the undesirable effects of CPF, through elevation of macrophage and serum lysozyme activities, increased the levels of IL-2 and IL-6, corrected the oxidative stress markers, and alleviated most of the adverse effect exerted by CPF in liver and spleen tissues. CONCLUSION: The addition of ZnO NPs to CPF-contaminated drinking water may be useful as a powerful antioxidant agent against toxic damage induced by CPF particularly in individuals who are on daily occupational exposure to low doses of CPF.

Antioxidants: Scientific Literature Landscape Analysis.

Antioxidants are abundant in natural dietary sources, and the consumption of antioxidants has a lot of potential health benefits. However, there has been no literature analysis on this topic to evaluate its scientific impact in terms of citations. This study is aimed at identifying and analysing the antioxidant publications in the existing scientific literature. In this context, a literature search was performed with the Web of Science database. Full records and cited references of the 299,602 identified manuscripts were imported into VOSviewer for bibliometric analysis. Most of the manuscripts were published since 1991. The publications were mainly related to the categories biochemistry/molecular biology, food science technology, and pharmacology/pharmacy. These topics have been prolific since 1990 and before. Polymer science was prolific before, but its publication share declined in the recent two decades. Brazil, China, India, and South Korea have emerged as upcoming major contributors besides USA. Most prolific journals were Food Chemistry, Journal of Agricultural and Food Chemistry, Free Radical Biology and Medicine, and PLOS One. Clinical conditions with high citations included Alzheimer's disease, cancer, cardiovascular disease, and Parkinson's disease. Chemical terms and structures with high citations included alpha-tocopherol, anthocyanin, ascorbate, beta-carotene, carotenoid, curcumin, cysteine, flavonoid, flavonol, hydrogen peroxide, kaempferol, N-acetylcysteine, nitric oxide, phenolic acid, uric acid, vitamin C, vitamin E, selenium, and resveratrol. Citation patterns temporal analysis revealed a transition of the scientific interest from research focused on antioxidant vitamins and minerals into stronger attention focus on antioxidant phytochemicals (plant secondary metabolites).

The role of apitoxin in alleviating propionic acid-induced neurobehavioral impairments in rat pups: The expression pattern of Reelin gene.

The efficacy of apitoxin (bee venom; BV) in ameliorating propionic acid (PPA) -induced neurobehavioral impacts was studied. Sixty rat pups were enrolled in a split litter design to six groups: a control group, a PPA-treated group, a BV-treated group, a BV/PPA protective group, a PPA/BV therapeutic group, and a BV/PPA/BV protective and therapeutic group. Exploratory, social, locomotor, and repetitive/stereotype-like activities were assessed and prosocial, empathy, and acquired behavior were evaluated. Levels of neurotransmitter including serotonin, dopamine, and gamma-aminobutyric acid (GABA) were determined and a quantitative analysis of Reelin gene expression was performed. PPA treatment induced several behavioral alterations, as reduced exploratory activity and social behaviors, increased repetitive/stereotypic behaviors, and hyperactivity. In addition, a marked decline of neurotransmitters and down-regulation of Reelin mRNA expression were observed. BV exhibited high efficiency in ameliorating the PPA-induced neurobehavioral alterations, particularly when applied both before and after PPA administration. Overall, the results implied that BV has merit as a candidate therapeutic treatment to alleviate PPA-induced neurobehavioral disorders.

Modulating effect of MgO-SiO2 nanoparticles on immunological and histopathological alterations induced by aflatoxicosis in rats.

INTRODUCTION: AflatoxinB1 (AFB1) is well-known as a feed borne-hepatotoxic and immunosuppressive mycotoxin. This study was conducted to evaluate the efficacy of nanocomposite magnesium oxide and silicon oxide (MgO-SiO2) in reducing the toxic effects of AFB1on the immunity and histological alterations in liver, spleen and intestine of adult male rats. EXPERIMENTAL DESIGN: Animals were divided into a control (Gp1) and three experimental groups (Gps); Gp2 received feed contained 200 ppb AFB1, Gp3 received feed contained 200 ppb AFB1 and 0.5 g/kg MgO-SiO2 nanocomposite. While, rats of Gp4 received feed contained 0.5 g/kg MgO-SiO2 nano-composite. METHODS: Cellular and humoral immune responses, as well as histopathological examination and caspase-3 expression in liver, spleen, and intestine, were all evaluated. Residual concentration of AFB1was determined in serum, liver and fecal samples. The obtained data were statistically analyzed. RESULTS: AFB1markedly reduced body weight gain and food and water consumption. Cellular immune response (total and differential leukocytes count, neutrophils' phagocytic activity, lymphocyte transformation, macrophage activity and serum lysozyme activity), serum total protein, and humoral immune response (fractions of protein as estimated by SDS- PAGE electrophoresis) were all severely reduced by AFB1. Moreover, AFB1induced marked histological alterations and apoptosis in liver, spleen, and intestine. CONCLUSION: These findings suggested that the nanocomposite MgO-SiO2 has high affinity to adsorb AFB1 and can effectively modulate its toxicity in rats. IMPACT STATEMENT: Nanocomposite MgO-SiO2 may offer a novel effective and cheap approach for the preventive management of aflatoxicosis in animals.

d-Amphetamine-induced cytotoxicity and oxidative stress in isolated rat hepatocytes.

Amphetamines (AMP) are potent psychostimulants and commonly used drugs of abuse. Its chronic administration creates tolerance and addiction and also associated with neurotoxicity and hepatocellular damage through oxidative stress. The present study was designed to evaluate the cytotoxic effects as well as the oxidative stress induced by d-amphetamines in isolated rat hepatocytes. Hepatocytes were isolated by collagenase perfusion technique and were exposed to different concentrations of AMP (0.2, 0.4, 0.8 and 1.6mM) in a time-course experiment for up to 2h. AMP exposure induced a significant decrease in cell viability and a significant increase in the leakage of hepatic enzymes {lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and asparate aminotransferase (AST)} in a concentration and time-related manner. In the same experiment, GSH content and thiobarbituric acid reactive substances (TBARS) generation were determined as indices of oxidative stress and lipid peroxidation respectively. AMP exposure results in a significant decrease in cellular GSH content as well as a significant enhancement of TBARS accumulation in a concentration and time-related manners. The obtained results suggested that 2-h exposure of hepatocytes to AMP (0.8mM) was accompanied by submaximal responses. Therefore, a subsequent dose-response experiment was designed to evaluate the role of GSH modulation and oxidative stress in AMP toxicity in hepatocytes at 2h. LDH release and TBARS generation were used as indicators in this experiment. Pretreatment with the GSH-depleting agents, chlorodinitrobenzene (CDNB), buthionine sulfoximine (BSO), or bis(chloroethyl)-nitrosurea (BCNU) enhanced the cytotoxicity of AMP. Conversely, pretreatment with GSH or sulfhydryl compounds such as methionine (MT), cysteine (CYS) or dithiothreitol (DTT) attenuated AMP toxicity. Similarly, co-incubation with enzymatic antioxidants, superoxide dismutase (SOD) or catalase (CAT) or iron chelator, desferroxiamine (DFO) or the hydroxyl radical scavengers, dimethylsulfoxide (DMSO) exhibited significant protection against AMP cytotoxicity. The present results indicate that AMP has a potential cytotoxic effect in isolated rat hepatocytes. AMP cytotoxicity is concentration-dependent. GSH depletion and oxidative stress play an important role in enhancing hepatotoxic potential of AMP in isolated rat hepatocyte. Thiol group-donors, antioxidants, free radical scavengers and iron chelators can play a critical role against AMP-induced cellular damage.

Effects of ammonium metavanadate on fertility and reproductive performance of adult male and female rats.

Vanadium is a ubiquitous trace metal present in most plant and animal tissues. Environmental exposure to trivalent and pentavalent inorganic vanadium compounds has been related to impaired different phases of reproduction. Therefore, the effects of a pentavalent inorganic vanadium compound on general reproductive performance and fertility were investigated in male and female rats. Sexually mature male and female rats were exposed to 200 ppm ammonium metavanadate in drinking water. Male rats were exposed for 70 days, while the female rats exposed for 14 days premating, during mating, and throughout the whole length of gestation and lactation periods till weaning. The effects on male sex organ weights and fertility were evaluated at the end of exposure period. However, the effects on female fertility as well as developmental and postnatal effects were evaluated throughout the exposure period. The fertility was significantly reduced in both treated groups, with more pronounced suppressive effects in the male treated group. The number of implantation sites and the number of viable fetuses were significantly reduced in pregnant females of both treated groups. However, the number of resorptions, dead fetuses, and pre- and postimplantation losses were significantly increased. The incidence of resorptions was significantly increased in treated female group compared with untreated female group. The behavioral responses as well as fetal survival and viability indices were decreased in both treated groups during the lactation period. The incidence of these effects was more pronounced in the treated female group. The morphological, visceral, and skeletal anomalies were recorded significantly increased in fetuses of both treated groups, with more pronounced effects on fetuses of treated females. In conclusion, the exposure of adult male and female rats to ammonium metavanadate would cause adverse effects on fertility and reproduction.

Neurotoxicologic sequelae of tributyltin intoxication in rats.

Tributyltin oxide (TBTO) is a commonly used biocide. The purpose of this study is to correlate the toxicity of TBTO with the alterations of brain neurotransmitters and ATPases. TBTO was given by stomach tube to rats at either 37.5 or 75 mg x kg (-1)for 3 consecutive days. Nervous signs appeared in treated animals and the mortality reached 12 and 30%, respectively. The levels of brain dopamine, norepinephrine and serotonin decreased in a dose-dependent manner. The activities of brain total ATPase, Mg (2+)-ATPase and Na (+)/K (+)- ATPase were suppressed. The activity of Na (+)/K (+)- ATPase was more severely affected than that of Mg (2+)-ATPase. Histopathological changes in brain included hyperaemia, focal haemorrhages in vacuolated myelinated fibres, chromatolysis, or complete necrosis of neurons, degenerative changes, or complete absence of purkinje cells in the cerebellum.