Hyperglycemia enhances the generation of ROS and RNS that impair antioxidant power and cause oxidative damage in human erythrocytes.

Hyperglycemia is a state in which excess glucose circulates in blood. Erythrocytes are in direct contact with this high glucose concentration and are greatly affected by it. We have examined the effect of hyperglycemic condition on isolated human erythrocytes under in vitro conditions. Erythrocytes were incubated with different concentrations of glucose (5, 15, 30, 45 mmol/L) for 24 h, and several biochemical parameters were determined. Treatment with high glucose concentrations increased heme degradation and methemoglobin level, while methemoglobin reductase activity was decreased. A significant increase in protein oxidation and lipid hydroperoxides with a decrease in total sulfhydryl content was seen. This suggested the generation of oxidative stress, which was confirmed by an enhanced production of reactive oxygen and nitrogen species. Hyperglycemia led to a significant decline in the antioxidant power of erythrocytes, lowering their ability to quench free radicals and reduce metal ions to lower oxidation states. The plasma membrane redox system was upregulated, while ascorbate free radical reductase activity was lowered. Glucose exposure inhibited the enzymes of glycolysis and hexose monophosphate shunt. Electron microscopy showed morphological changes resulting in the formation of echinocytes. Thus, the hyperglycemic condition generates reactive species that oxidize proteins, hemoglobin, and lipids; impair the total antioxidant capacity; and alter morphology in human erythrocytes.

Pentachlorophenol causes redox imbalance, inhibition of brush border membrane and metabolic enzymes, DNA damage and histological alterations in rat kidney.

Pentachlorophenol (PCP) is a synthetic organochlorine compound that is widely used in biocide and pesticide industries, and in preservation of wood, fence posts, cross arms and power line poles. Humans are usually exposed to PCP through air, contaminated water and food. PCP enters the body and adversely affects liver, gastrointestinal tract, kidney and lungs. PCP is a highly toxic class 2B or probable human carcinogen that produces large amount of reactive oxygen species (ROS) within cells. This work aimed to determine PCP-induced oxidative damage in rat kidney. Adult rats were given PCP (25, 50, 100, 150 mg/kg body weight), in corn oil, once a day for 5 days while control rats were given similar amount of corn oil by oral gavage. PCP increased hydrogen peroxide level and oxidation of thiols, proteins and lipids. The antioxidant status of kidney cells was compromised in PCP treated rats while enzymes of brush border membrane (BBM) and carbohydrate metabolism were inhibited. Plasma level of creatinine and urea was also increased. Administration of PCP increased DNA fragmentation, cross-linking of DNA to proteins and DNA strand scission in kidney. Histological studies supported biochemical findings and showed significant damage in the kidneys of PCP-treated rats. These changes could be due to redox imbalance or direct chemical modification by PCP or its metabolites. These results signify that PCP-induced oxidative stress causes nephrotoxicity, dysfunction of BBM enzymes and DNA damage.

Protective effect of rutin against thiram-induced cytotoxicity and oxidative damage in human erythrocytes.

Thiram is a fungicide that is used to prevent fungal diseases in seeds and crops and also as an animal repellent. The pro-oxidant activity of thiram is well established. Rutin is a flavonoid glycoside present in many fruits and plants and has several beneficial properties, including antioxidant effects. We have previously shown that thiram causes oxidative damage in human erythrocytes. The present study was designed to evaluate the protective effect of rutin against thiram-induced damage in human erythrocytes. Treatment of erythrocytes with 0.5 mM thiram for 4 h increased the level of oxidative stress markers, decreased antioxidant power and lowered the activity of antioxidant and membrane bound enzymes. It also enhanced the generation of reactive oxygen and nitrogen species (ROS and RNS) and altered the morphology of erythrocytes. However, prior treatment of erythrocytes with rutin (0.5, 1 and 2 mM) for 2 h, followed by 4 h incubation with 0.5 mM thiram, led to a decrease in the level of oxidative stress markers in a rutin concentration-dependent manner. A significant restoration in the antioxidant power and activity of antioxidant enzymes was observed upon the treatment of erythrocytes with 1 and 2 mM rutin. Pre-incubation with rutin lowered the generation of ROS and RNS which will reduce oxidative damage in erythrocytes. The thiram-induced changes in cell morphology and activity of membrane-bound enzymes were also attenuated by rutin. These results suggest that rutin can be used to mitigate thiram-induced oxidative damage in human erythrocytes.

Mancozeb-induced cytotoxicity in human erythrocytes: enhanced generation of reactive species, hemoglobin oxidation, diminished antioxidant power, membrane damage and morphological changes.

Mancozeb is an ethylene bis-dithiocarbamate fungicide extensively used in agriculture to safeguard crops from various fungal diseases. The general population is exposed to mancozeb through consumption of contaminated food or water. Here, we have investigated the effect of mancozeb on isolated human erythrocytes under in vitro conditions. Erythrocytes were treated with different concentrations of mancozeb (0, 5, 10, 25, 50, 100 µM) and incubated for 24 h at 37 °C. Analysis of biochemical parameters and cell morphology showed dose-dependent toxicity of mancozeb in human erythrocytes. Mancozeb treatment caused hemoglobin oxidation and heme degradation. Protein and lipid oxidation were enhanced, while a significant decrease was seen in reduced glutathione and total sulfhydryl content. A significant increase in the generation of reactive oxygen and nitrogen species was detected in mancozeb-treated erythrocytes. The antioxidant capacity and the activity of key antioxidant enzymes were greatly diminished, while crucial metabolic pathways were inhibited in erythrocytes. Damage to the erythrocyte membrane on mancozeb treatment was apparent from increased cell lysis and osmotic fragility, along with the impairment of the plasma membrane redox system. Mancozeb also caused morphological alterations and transformed the normal discoid-shaped erythrocytes into echinocytes and stomatocytes. Thus, mancozeb induces oxidative stress in human erythrocytes, impairs the antioxidant defense system, oxidizes cellular components, that will adversely affect erythrocyte structure and function.

Esculin protects human blood cells from bioallethrin-induced toxicity: An ex vivo study.

Bioallethrin, a household insecticide, is a member of the pyrethroid family and is known for its adverse effects on human health. Human exposure to pyrethroids is unavoidable due to their widespread use in controlling several fatal vector-borne diseases, mostly in developing nations. Bioallethrin is known to induce oxidative stress in target cells, including erythrocytes. Here we have studied the protective effect of dietary antioxidant esculin on bioallethrin-induced damage in isolated human erythrocytes. The cells were incubated with 200 µM bioallethrin, without or with different concentrations of esculin (200, 400 and 600 µM), and the results compared to the untreated control samples. Bioallethrin-treated erythrocytes showed a significant increase in oxidative stress markers, like protein and lipid oxidation, accompanied by decrease in free amino groups and ratio of reduced to oxidized glutathione. There was enhanced generation of reactive oxygen and nitrogen species with changes in plasma membrane integrity. Bioallethrin oxidized hemoglobin to methemoglobin, which cannot transport oxygen. It altered the activities of antioxidant enzymes and lowered the electron donating and free radical quenching ability of erythrocytes. The cell morphology and redox system of erythrocyte membrane were also altered by bioallethrin. Treatment with esculin, prior to incubation with bioallethrin, led to significant restoration in all these parameters in an esculin concentration-dependent manner. Thus esculin attenuated the biolletherin-induced oxidative damage to erythrocytes. Esculin can, therefore, be an effective chemoprotectant against xenobiotic-induced toxicity in human erythrocytes.

Attenuation of Hg(II)-induced cellular and DNA damage in human blood cells by uric acid.

Mercury (Hg) is a widespread environmental pollutant and toxicant that induces multiple organ damage in humans and animals. Hg toxicity is mediated by the induction of oxidative stress in the target cells. We used uric acid (UA), a potent antioxidant found in biological fluids, to protect human red blood cells (RBC) and lymphocytes against Hg-mediated cell, organelle, and genotoxicity. RBCs were incubated with mercuric chloride (HgCl2), an Hg(II) compound, either alone or in the presence of UA. Incubation of RBCs with only HgCl2 increased the production of nitrogen and oxygen radical species, enhanced methemoglobin levels, heme degradation, free ferrous iron, oxidation of proteins and membrane lipids, and reduced the antioxidant capacity of cells. UA enhanced the antioxidant capacity of RBCs and restored metabolic, plasma membrane-bound, and antioxidant enzyme activities. Scanning electron microscopy showed that UA prevented HgCl2-mediated morphological changes in RBCs. HgCl2 dissipated the mitochondrial membrane potential and increased lysosomal membrane damage in lymphocytes, but UA pre-treatment attenuated these effects. Genotoxicity analysis by comet assay showed that UA protected lymphocyte DNA from HgCl2-induced damage. Importantly, UA itself did not exhibit any deleterious effects on RBCs or lymphocytes. Thus, UA protects human blood cells from Hg(II)-mediated oxidative damage, reducing the harmful effects of this extremely toxic metal. We suggest that UA has a similar protective role in plasma against heavy metal toxicity.

Cadmium chloride generates cytotoxic reactive species that cause oxidative damage and morphological changes in human erythrocytes.

Cadmium chloride (CdCl2) is a widely used industrial compound that exhibits multiple organ toxicity. Cadmium is transported through blood where erythrocytes are exposed to its action. Here the effect of CdCl2 on human erythrocytes was examined under in vitro conditions. Human erythrocytes were treated with 0.01-0.5 mM CdCl2 for 24 h at 37 °C. Lysates were made from CdCl2 treated and untreated (control) cells and used for further analysis. CdCl2 treatment resulted in marked hemolysis of erythrocytes and oxidation of hemoglobin to methemoglobin. This will result in anemia and also reduce the oxygen carrying ability of erythrocytes. Hemoglobin oxidation was accompanied by degradation of heme and release of free ferrous iron moiety. Further analysis showed elevated lipid hydroperoxides and formation of advanced oxidation protein products along with reduction in total sulfhydryl content, indicating the generation of oxidative stress condition in the cell. Incubation of erythrocytes with CdCl2 enhanced generation of reactive oxygen and nitrogen species, decreased the antioxidant power and inhibited pathways of glucose metabolism. Plasma membrane was damaged as indicated by enhanced osmotic fragility and inhibition of membrane bound enzymes. This was confirmed by electron microscopy which showed formation of echinocytes. These results show that CdCl2 generates reactive species which impair the antioxidant system resulting in oxidative damage to erythrocytes.

Cytoprotective effect of taurine against sodium chlorate-induced oxidative damage in human red blood cells: an ex vivo study.

Sodium chlorate (NaClO3) is a common non-selective herbicide that is also used in paper and pulp mills and is produced as a by-product during drinking water disinfection by chlorine dioxide. Here, we report the effect of dietary antioxidant taurine on NaClO3-induced cytotoxicity in human red blood cells (RBC). RBC were treated with 5 mM NaClO3, either alone or in presence of 1, 2.5 and 5.0 mM taurine. Incubation of RBC with NaClO3 alone caused hemolysis, increased oxidation of lipids and proteins, methemogobin level and decreased total sulfhydryl and glutathione content. It lowered the activities of antioxidant enzymes thioredoxin reductase, glutathione peroxidase, catalase and glutathione reductase, while Cu-Zn superoxide dismutase activity was increased. The antioxidant capacity of RBC was impaired. This strongly suggests that NaClO3 causes the induction of oxidative stress condition in RBC. The specific activities of lactate dehydrogenase, glucose 6-phosphate dehydrogenase and plasma membrane bound enzymes, were also greatly altered. However, prior treatment of RBC with taurine conferred significant protection against NaClO3-induced oxidative damage and also improved the antioxidant defence system of cells. These results were supported by electron microscopy images of RBC. Treatment with NaClO3 alone converted the normal biconcave discoidal RBC to acanthocytes and echinocytes but this transformation was greatly prevented in the presence of taurine. Thus, taurine mitigates the cytotoxicity of NaClO3 in human RBC and can function as an effective chemoprotectant.

Carbendazim toxicity in different cell lines and mammalian tissues.

The extensive production and use of harmful pesticides in agriculture to improve crop yield has raised concerns about their potential threat to living components of the environment. Pesticides cause serious environmental and health problems both to humans and animals. Carbendazim (CBZ) is a broad spectrum fungicide that is used to control or effectively kill pathogenic microorganisms. CBZ is a significant contaminant found in food, soil and water. It exerts immediate and delayed harmful effects on humans, invertebrates, aquatic animals and soil microbes when used extensively and repeatedly. CBZ is a teratogenic, mutagenic and aneugenic agent that imparts its toxicity by enhancing generation of reactive oxygen species generation. It elevates the oxidation of thiols, proteins and lipids and decreases the activities of antioxidant enzymes. CBZ is cytotoxic causing hematological abnormalities, mitotic spindle deformity, inhibits mitosis and alters cell cycle events which lead to apoptosis. CBZ is known to cause endocrine-disruption, embryo toxicity, infertility, hepatic dysfunction and has been reported to be one of the leading causes of neurodegenerative disorders. CBZ is dangerous to human health, the most common side effects upon chronic exposure are thyroid gland dysfunction and oxidative hepato-nephrotoxicity. In mammals, CBZ has been shown to disrupt the antioxidant defense system. In this review, CBZ-induced toxicity in different cells, tissues and organisms, under in vitro and in vivo conditions, has been systematically discussed.

3,4-Dihydroxybenzaldehyde attenuates pentachlorophenol-induced cytotoxicity, DNA damage and collapse of mitochondrial membrane potential in isolated human blood cells.

Pentachlorophenol (PCP) is a chlorophenolic compound that is widely used as pesticide, biocide and as a wood preservative to treat utility poles and wharf pilings. PCP is rapidly absorbed through the gastrointestinal tract and enters the blood where it generates active oxygen species in target cells. We have, therefore, examined the protective effect of plant antioxidant 3,4-dihydroxybenzaldehyde (DHB) against PCP-induced cyto-and geno-toxicity in human red blood cells (RBC) and lymphocytes, respectively. Human RBC were incubated at 37°C with 0.75 mM PCP, either alone or in presence of different concentrations of DHB (0.05-2.0 mM). Several biochemical parameters were determined in whole cells and hemolysates. Incubation of RBC with PCP alone increased the formation of reactive oxygen and nitrogen species (ROS and RNS) that resulted in oxidation of proteins, lipids, cellular thiols and plasma membrane damage. The antioxidant defense system was impaired and glucose metabolism was inhibited. However, prior treatment of RBC with DHB lowered ROS and RNS generation and attenuated PCP-induced oxidative damage of cell components. DHB alone enhanced electron transport by the plasma membrane redox system and also prevented its inhibition by PCP. DHB significantly prevented PCP-induced transformation of RBC morphology from normal biconcave shape to spherocytes, spiculated acanthocytes and echinocytes. DHB protected human lymphocytes from PCP-induced DNA damage and strand breaks, lysosomal membrane damage and collapse of the mitochondrial membrane potential. These results show that DHB mitigates PCP-induced cytotoxicity and can potentially function as a chemoprotective agent against the harmful effects of PCP and possibly other chlorophenols.

Fluoride enhances generation of reactive oxygen and nitrogen species, oxidizes hemoglobin, lowers antioxidant power and inhibits transmembrane electron transport in isolated human red blood cells.

Fluoride is a widespread environmental pollutant that at high levels exerts numerous deleterious effects on human health. The toxic effects of fluoride are a matter of serious concern since many countries have regions of endemic fluorosis. The main source of fluoride exposure for humans is intake of contaminated groundwater. Fluoride is absorbed from the gastrointestinal tract and enters the circulating blood, where the abundant red blood cells (RBC) are an early and major target of fluoride toxicity. Chronic fluoride exposure generates free radicals, reactive species which leads to redox imbalance, cytotoxicity and hematological damage. This study aimed to determine the effect of sodium fluoride (NaF) on human RBC under in vitro conditions. Isolated RBC were incubated with different concentrations of NaF (10-500 µM) for 8 h at 37 °C. Several biochemical parameters were determined in hemolysates or whole cells. Treatment of RBC with NaF enhanced the generation of reactive oxygen and nitrogen species. This increased the oxidation of hemoglobin to yield methemoglobin and oxoferrylhemoglobin, which are inactive in oxygen transport. NaF treatment increased the degradation of heme causing release of free iron from its porphyrin ring. Cellular antioxidant power was significantly decreased in NaF-treated RBC, lowering the metal reducing and free radical quenching ability of cells. The two pathways of glucose metabolism in RBC i.e. glycolysis and hexose monophosphate shunt, were inhibited. NaF also inhibited the plasma membrane redox system, and its associated ascorbate free radical reductase, to disrupt transmembrane electron transport. These results suggest that fluoride generates reactive species that cause extensive oxidative modifications in human RBC.

Oral administration of thiram inhibits brush border membrane enzymes, oxidizes proteins and thiols, impairs redox system and causes histological changes in rat intestine: A dose dependent study.

Pesticides are extensively employed worldwide, especially in agriculture to control weeds, insect infestation and diseases. Besides their targets, pesticides can also affect the health of non-target organisms, including humans The present study was conducted to study the effect of oral exposure of thiram, a dithiocarbamate fungicide, on the intestine of rats. Male rats were administered thiram at doses of 100, 250, 500 and 750 mg/kg body weight for 4 days. This treatment reduced cellular glutathione, total sulfhydryl groups but enhanced protein carbonyl content and hydrogen peroxide levels. In addition, the activities of all major antioxidant enzymes (catalase, thioredoxin reductase, glutathione peroxidase and glutathione-S-transferase) except superoxide dismutase were decreased. The antioxidant power of the intestine was impaired lowering the metal-reducing and free radical quenching ability. Administration of thiram also led to inhibition of intestinal brush border membrane enzymes, alkaline phosphatase, γ-glutamyl transferase, leucine aminopeptidase and sucrase. Activities of enzymes of pentose phosphate pathway, citric acid cycle, glycolysis and gluconeogenesis were also inhibited. Histopathology showed extensive damage in the intestine of thiram-treated rats at higher doses. All the observed effects were in a thiram dose-dependent manner. The results of this study show that thiram causes significant oxidative damage in the rat intestine which is associated with the marked impairment in the antioxidant defense system.

An overview of Covid-19 pandemic: immunology and pharmacology.

In this review, we present an elaborate account of coronavirus in context to Covid-19 focusing on its origin, genome, life cycle, and immunology with a basic understanding of the disease and its cause. Further, the transmission, prevention and advances in therapeutics have also been discussed anticipating the possible outcomes in the near future. Moreover, the recently emerged unconventional approaches to this viral disease like drug repurposing, plasma therapy, nasal spray, and other preventive measures worldwide are studied for a long-term impact and relevance. Hence, this account on coronavirus and the ongoing pandemic serves a purpose of spreading awareness and to pass on relevant knowledge for a better chance to combat such unfortunate health crisis in future.

Taurine attenuates Cr(VI)-induced cellular and DNA damage: an in vitro study using human erythrocytes and lymphocytes.

Hexavalent chromium [(Cr(VI)] is widely used in several industries, but human exposure results in multiple organ toxicity. Enhanced generation of free radicals and reactive species is thought to play a key role in Cr(VI)-induced toxicity. We have examined the effect of taurine, a simple sulphur-containing amino acid and an antioxidant, on potassium dichromate [K2Cr2O7, a Cr(VI) compound]-induced cytotoxicity and genotoxicity in human blood cells. Erythrocytes were treated with K2Cr2O7, either alone or after incubation with different concentrations of taurine. Treatment of erythrocytes with K2Cr2O7 alone led to marked increase in generation of reactive oxygen and nitrogen species, lipid and protein oxidation. This was accompanied by decrease in total sulfhydryl and glutathione content and lowered antioxidant power of the cells. This suggests that Cr(VI) induces oxidative stress in the cells. Incubation of erythrocytes with taurine prior to addition of K2Cr2O7, resulted in a concentration-dependent decrease in the generation of reactive oxygen and nitrogen species, mitigation of oxidative stress and amelioration of antioxidant power of these cells. It also restored the activities of several metabolic, antioxidant and membrane-bound enzymes. Cr(VI)-induced damage to erythrocyte membrane and lymphocyte DNA was also significantly attenuated by prior administration of taurine. These results suggest that taurine can function as a chemoprotectant against Cr(VI)-induced oxidative injury and can be potentially used to mitigate the toxic effects of this transition metal ion.

Thiram-induced cytotoxicity and oxidative stress in human erythrocytes: an in vitro study.

Tetramethylthiuram disulfide, commonly known as thiram, is an organosulfur compound which is used as a bactericide, fungicide and ectoparasiticide to prevent disease in seeds and crops. Being a fungicide there is a high probability of human occupational exposure to thiram and also via consumption of contaminated food. In this work, the cytotoxicity of thiram was studied under in vitro conditions using human erythrocytes as the cellular model. Erythrocytes were incubated with different concentrations of thiram (25-500 µM) for 4 h at 37 °C. Control cells (thiram untreated) were similarly incubated at 37 °C. Whole cells and hemolysates were analyzed for various biochemical parameters. Treatment of erythrocytes with thiram increased protein and lipid oxidation and hydrogen peroxide level in hemolysates but decreased glutathione and total sulfhydryl group content. This was accompanied by hemoglobin oxidation, heme degradation and release of free iron. Activities of all major antioxidant enzymes were inhibited. The antioxidant power of thiram treated erythrocytes was lowered resulting in decreased metal reducing and free radical quenching ability. These results suggest that thiram enhances the generation of reactive species that cause oxidative modification of cell components. This was confirmed by experiments that showed enhanced generation of reactive oxygen and nitrogen species in thiram treated erythrocytes. Activities of marker enzymes of glucose metabolism and erythrocyte membrane were also inhibited. All effects were seen in a thiram concentration-dependent manner. Electron microscopy further supported the damaging effect of thiram on erythrocytes. Thus thiram induces oxidative stress condition in human erythrocytes and causes oxidative modification of cell components.

Ameliorative effect of carnosine and N-acetylcysteine against sodium nitrite induced nephrotoxicity in rats.

The widespread use of sodium nitrite (NaNO2 ) for various industrial purposes has increased human exposure to alarmingly high levels of nitrate/nitrite. Because NaNO 2 is a strong oxidizing agent, induction of oxidative stress is one of the mechanisms by which it can exert toxicity in humans and animals. We have investigated the possible protection offered by carnosine (CAR) and N-acetylcysteine (NAC) against NaNO 2 -induced nephrotoxicity in rats. Animals orally received CAR at 100 mg/kg body weight/d for seven days or NAC at 100 mg/kg body weight/d for five days followed by a single oral dose of NaNO 2 at 60 mg/kg body weight. The rats were killed after 24 hours, and the kidneys were removed and processed for various analyses. NaNO 2 induced oxidative stress in kidneys, as shown by the decreased activities of antioxidant defense, brush border membrane, and metabolic enzymes. DNA-protein crosslinking and DNA fragmentation were also observed. CAR/NAC pretreatment significantly protected the kidney against these biochemical alterations. Histological studies supported these findings, showing kidney damage in NaNO 2 -treated animals and reduced tissue impairment in the combination groups. The protection offered by CAR and NAC against NaNO 2 -induced damage, and their nontoxic nature, makes them potential therapeutic agents against nitrite-induced nephrotoxicity.

Acute oral dose of sodium nitrite causes redox imbalance and DNA damage in rat kidney.

Sodium nitrite (NaNO2 ) is widely used as a food additive and preservative in fish and meat products. We have evaluated the effect of a single acute oral dose of NaNO2 on oxidative stress parameters, antioxidant capacity, and DNA in rat kidney. Male Wistar rats were divided into four groups and given single oral dose of NaNO2 at 20, 40, 60, and 75 mg/kg body weight; untreated rats served as the control group. All animals in NaNO2 -treated groups showed marked alterations in various parameters of oxidative stress as compared to the control group. This included increase in lipid peroxidation, protein oxidation, hydrogen peroxide levels, and decrease in reduced glutathione content and antioxidant capacity. Administration of NaNO2 also increased DNA damage as evident from release of free nucleotides and confirmed by comet assay. It also led to greater cross-linking of DNA to proteins. Histological analysis showed marked morphological changes in the kidney of NaNO2 -treated animals. These alterations could be due to increased free radical generation or direct chemical modification by reaction intermediates. Our results suggest that nitrite-induced nephrotoxicity is mediated through redox imbalance and results in DNA damage.

Reliability of the triple-timed up-and-go test.

INTRODUCTION: We report the reliability of a new measure, the triple-timed up-and-go (3TUG) test, for assessing clinical function in patients with Lambert-Eaton myasthenia (LEM). METHODS: Intrarater reproducibility and interrater agreement of the 3TUG test were assessed in 25 control participants, 24 patients with non-LEM neuromuscular disease, and 12 patients with LEM. The coverage probability (CP) method was the primary measure of reproducibility and agreement. The a priori acceptable range was < 20% difference in 3TUG test times and a CP ≥0.90 confirmed agreement. RESULTS: CP values > 0.90 for intrarater and interrater tests confirmed acceptable reproducibility and agreement for all groups. DISCUSSION: The 3TUG test is a quick, noninvasive, and reproducible measure that is easy to perform, measures clinically important weakness in LEM patients, and requires little training. Additional evaluation in a larger number of LEM patients is in progress to validate the 3TUG test as a clinical measure in LEM. Muscle Nerve 57: 136-139, 2017.

Carnosine and N-acetyl cysteine protect against sodium nitrite-induced oxidative stress in rat blood.

Sodium nitrite (NaNO2 ) is widely used in the food industry as a preservative and colorant in meat and fish products. Industrialization and improper agricultural practices have greatly increased human exposure to high nitrite levels, mainly through contaminated drinking water, causing various health disorders. We have investigated the protective effect of carnosine (CAR) and N-acetyl cysteine (NAC) on NaNO2 -induced toxicity in rat blood. CAR is a bioactive dipeptide found in mammalian muscle while NAC is a synthetic sulfhydryl amino acid and an important precursor of glutathione. Animals were given a single acute oral dose of NaNO2 at 60 mg/kg body weight with or without prior administration of either CAR or NAC. Rats were sacrificed after 24 h, blood was withdrawn and plasma and erythrocytes were isolated. Administration of NaNO2 alone increased methemoglobin levels and methemoglobin reductase activity, decreased the activities of antioxidant defense and metabolic enzymes and significantly weakened the total antioxidant capacity of rat erythrocytes. Similar effects were seen in plasma of NaNO2 -treated rats. In contrast, administration of CAR or NAC, prior to NaNO2 treatment, markedly attenuated the NaNO2 -elicited deleterious effects. Thus, CAR and NAC can mitigate nitrite-induced metabolic alterations and oxidative damage probably due to their intrinsic biochemical antioxidant properties. This study suggests that CAR and NAC can be potentially used as therapeutic/protective agents against NaNO2 toxicity.

3,4-Dihydroxybenzaldehyde lowers ROS generation and protects human red blood cells from arsenic(III) induced oxidative damage.

Arsenic (As) is a potent environmental toxicant and chronic exposure to it results in various malignancies in humans. Oxidative stress has been implicated in the etiopathogenesis of As-induced toxicity. This investigated the protective effect of plant antioxidant 3,4-dihydroxybenzaldehyde (DHB) on sodium meta-arsenite (SA), an As-(III) compound, induced oxidative damage in human red blood cells (RBC). The RBC were first incubated with different concentrations of DHB and then treated with SA at 37°C. Hemolysates were prepared and assayed for various biochemical parameters. Treatment of RBC with SA alone enhanced the generation of reactive oxygen species and increased lipid and protein oxidation. Reduced glutathione levels, total sulfhydryl content and cellular antioxidant power were significantly decreased in SA alone treated RBC, compared to the untreated control cells. This was accompanied by membrane damage, alterations in activities of antioxidant enzymes and deranged glucose metabolism. Incubation of RBC with DHB, prior to treatment with SA, significantly and dose-dependently attenuated the SA-induced changes in all these parameters. Scanning electron microscopy of RBC confirmed these biochemical results. Treatment of RBC with SA alone converted the biconcave discoids to echinocytes but the presence of DHB inhibited this conversion and the RBC retained their normal shape. These results show that DHB protects human RBC from SA-induced oxidative damage, most probably due to its antioxidant character.