ABSTRACT
Soil pollution with heavy metals has grown to be a big hassle, leading to the loss in farming production particularly in developing countries like Pakistan, where no proper channel is present for irrigation and extraction of these toxic heavy metals. The present study aims to ameliorate the damages caused by heavy metal ions (Hg-Mercury) on rapeseed (Brassica napus L.) via a growth regulator (α-tocopherol 150 mg/L) and thermopriming technique at 4 °C and 50 °C to maintain plant agronomical and physiological characteristics. In pot experiments, we designed total of 11 treatments viz.( T0 (control), T1 (Hg4ppm), T2 (Hg8ppm), T3 (Hg4ppm + 4 °C), T4 (Hg4ppm + 4 °C + tocopherol (150 m/L)), T5 (Hg4ppm + 50 °C), T6 (Hg4ppm + 50 °C + tocopherol (150 mg/L)), T7 (Hg8ppm + 4 °C), T8 (Hg8ppm + 4 °C + tocopherol (150 mg/L)), T9 (Hg8ppm + 50 °C), T10 (Hg8ppm + 50 °C + tocopherol (150 mg/L) the results revealed that chlorophyll content at p < 0.05 with growth regulator and antioxidant enzymes such as catalase, peroxidase, and malondialdehyde enhanced up to the maximum level at T5 = Hg4ppm + 50 °C (50 °C thermopriming under 4 ppm mercuric chloride stress), suggesting that high temperature initiate the antioxidant system to reduce photosystem damage. However, protein, proline, superoxide dismutase at p < 0.05, and carotenoid, soluble sugar, and ascorbate peroxidase were increased non-significantly (p > 0.05) 50 °C thermopriming under 8 ppm high mercuric chloride stress (T9 = Hg8ppm + 50 °C) representing the tolerance of selected specie by synthesizing osmolytes to resist oxidation mechanism. Furthermore, reduction in % MC (moisture content) is easily improved with foliar application of α-tocopherol and 50 °C thermopriming and 4 ppm heavy metal stress at T6 = Hg4ppm + 50 °C + α-tocopherol (150 mg/L), with a remarkable increase in plant vigor and germination energy. It has resulted that the inhibitory effect of only lower concentration (4 ppm) of heavy metal stress was ameliorated by exogenous application of α-tocopherol and thermopriming technique by synthesizing high levels of proline and antioxidant activities in maintaining seedling growth and development on heavy metal contaminated soil.
Subject(s)
Brassica napus , Metals, Heavy , Soil Pollutants , Antioxidants/metabolism , alpha-Tocopherol/pharmacology , alpha-Tocopherol/metabolism , Brassica napus/metabolism , Mercuric Chloride/toxicity , Mercuric Chloride/metabolism , Tocopherols/metabolism , Tocopherols/pharmacology , Metals, Heavy/metabolism , Proline/metabolism , Soil Pollutants/metabolismABSTRACT
In this study, a zebrafish embryo toxicity model was employed, utilizing 24 h postfertilization (hpf) zebrafish embryos. These embryos were treated with varying concentrations of mercuric chloride for 96 h under static conditions. We assessed multiple parameters that reflected developmental abnormalities, behavioral alterations, morphological anomalies, antioxidant enzyme activities, including those of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione S-transferase (GST), immune messenger RNA transcription levels of key factors such as tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and cyclooxygenase 2 (COX-2), as well as protein expression of TNF-α. The results revealed that embryos exposed to higher concentrations of mercury exhibited reduced hatchability and increased rates of morphological abnormalities and mortality at 48, 72, and 96 hpf. In addition, a concentration-dependent increase in developmental abnormalities, including cardiac edema, reduced body length, yolk sac edema, scoliosis, and bent tails, was observed. Larval behaviors, such as touch-induced escape responses, startle reactions, and turning actions, were found to be diminished in a concentration-dependent manner. Additionally, the activities of various antioxidative enzymes, such as SOD, CAT, and GST, exhibited an increase at higher mercury concentrations, with the exception of GPX activity, which decreased significantly in a dose-dependent manner (p < 0.05). Pro-inflammatory cytokine transcription levels, specifically TNF-α, IL-1ß, IL-6, and COX-2, were significantly upregulated in a dose-dependent manner in the mercuric (II) chloride (HgCl2 ) treatment group compared with the control group. TNF-α protein expression was notably elevated in the larvae group treated with 300 and 400 nM HgCl2 .
Subject(s)
Antioxidants , Zebrafish , Animals , Antioxidants/pharmacology , Zebrafish/metabolism , Mercuric Chloride/toxicity , Chlorides/pharmacology , Oxidative Stress , Cytokines/metabolism , Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Embryo, Nonmammalian , Superoxide Dismutase/metabolismABSTRACT
Mercury chloride is a type of heavy metal that causes the formation of free radicals, causing hepatotoxicity, nephrotoxicity and apoptosis. In this study, the effects of naringenin on oxidative stress and apoptosis in the liver and kidney of rats exposed to mercury chloride were investigated. In the study, 41 2-month-old male Wistar-Albino rats were divided into five groups. Accordingly, group 1 was set as control group, group 2 as naringenin-100, group 3 as mercury chloride, group 4 as mercury chloride + naringenin-50, and group 5 as mercury chloride + naringenin-100. For the interventions, 1 mL/kg saline was administered to the control, 0.4 mg/kg/day mercury (II) chloride to the mercury chloride groups by i.p., and 50 and 100 mg/kg/day naringenin prepared in corn oil to the naringenin groups by gavage. All the interventions lasted for 20 days. Mercury chloride administration was initiated 1 h following the administration of naringenin. When mercury chloride and the control group were compared, a significant increase in plasma urea, liver and kidney malondialdehyde (MDA) levels, in kidney superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) activities (p < .001), and a significant decrease in liver and kidney glutathione (GSH) levels (p < .001), in liver catalase (CAT) activity (p < .01) were observed. In addition, histopathological changes and a significant increase in caspase-3 levels were detected (p < .05). When mercury chloride and treatment groups were compared, the administration of naringenin caused a decrease aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) (p < .01), urea, creatinine levels (p < .001) in plasma, MDA levels in liver and kidney, SOD, GSH-Px, GST activities in kidney (p < .001), and increased GSH levels in liver and kidney. The addition of naringenin-100 increased GSH levels above the control (p < .001). The administration of naringenin was also decreased histopathological changes and caspase-3 levels (p < .05). Accordingly, it was determined that naringenin is protective and therapeutic against mercury chloride-induced oxidative damage and apoptosis in the liver and kidney, and 100 mg/kg naringenin is more effective in preventing histopathological changes and apoptosis.
Subject(s)
Chlorides , Flavanones , Mercury , Rats , Male , Animals , Chlorides/metabolism , Caspase 3/metabolism , Rats, Wistar , Mercuric Chloride/toxicity , Mercuric Chloride/metabolism , Oxidative Stress , Antioxidants/metabolism , Kidney , Liver , Glutathione/metabolism , Superoxide Dismutase/metabolism , Apoptosis , Mercury/metabolism , Mercury/pharmacology , UreaABSTRACT
Mercury is a highly toxic element that induces severe alterations and a broad range of adverse effects on health. Its exposure is a global concern because it is widespread in the environment due to its multiple industrial, domestic, agricultural and medical usages. Among its various chemical forms, both humans and animals are mainly exposed to mercury chloride (HgCl2), methylmercury and elemental mercury. HgCl2 is metabolized primarily in the liver. We analysed the effects on the nuclear architecture of an increasing dosage of HgCl2 in mouse hepatocytes cell culture and in mouse liver, focusing specifically on the organization, on some epigenetic features of the heterochromatin domains and on the nucleolar morphology and activity. Through the combination of molecular and imaging approaches both at optical and electron microscopy, we show that mercury chloride induces modifications of the heterochromatin domains and a decrease of some histones post-translational modifications associated to heterochromatin. This is accompanied by an increase in nucleolar activity which is reflected by bigger nucleoli. We hypothesized that heterochromatin decondensation and nucleolar activation following mercury chloride exposure could be functional to express proteins necessary to counteract the harmful stimulus and reach a new equilibrium.
Subject(s)
Mercuric Chloride , Mercury , Humans , Mice , Animals , Mercuric Chloride/toxicity , Heterochromatin , Chlorides/pharmacology , Mercury/toxicity , LiverABSTRACT
Mercury is a toxic, environmentally heavy metal that can cause severe damage to all organs, including the nervous system. The functions of puerarin include antioxidant, anti-inflammatory, nerve cell repair, regulation of autophagy, and so forth. But because of the limited oral absorption of puerarin, it affects the protective effect on brain tissue. The nano-encapsulation of Pue can improve its limitation. Therefore, this study investigated the protective effect of Pue drug-loaded PLGA nanoparticles (Pue-PLGA-nps) on brain injury induced by mercuric chloride (HgCl2 ) in mice. The mice were divided into normal saline (NS) group, HgCl2 (4 mg/kg) group, Pue-PLGA-nps (50 mg/kg) group, HgCl2 + Pue (4 mg/kg + 30 mg/kg) group, and HgCl2 + Pue-PLGA-nps (4 mg/kg + 50 mg/kg) group. After 28 days of treatment, the mice were observed for behavioral changes, antioxidant capacity, autophagy and inflammatory response, and mercury levels in the brain, blood, and urine were measured. The results showed that HgCl2 toxicity caused learning and memory dysfunction in mice, increased mercury content in brain and blood, and increased serum levels of interleukin (IL-6), IL-1ß, and tumor necrosis factor-α in the mice. HgCl2 exposure decreased the activity of T-AOC, superoxide dismutase, and glutathione peroxidase, and increased the expression of malondialdehyde in the brain of mice. Moreover, the expression levels of TRIM32, toll-like receptor 4 (TLR4), and LC3 proteins were upregulated. Both Pue and Pue-PLGA-nps interventions mitigated the changes caused by HgCl2 exposure, and Pue-PLGA-nps further enhanced this effect. Our results suggest that Pue-PLGA-nps can ameliorate HgCl2 -induced brain injury and reduce Hg accumulation, which is associated with inhibition of oxidative stress, inflammatory response, and TLR4/TRIM32/LC3 signaling pathway.
Subject(s)
Brain Injuries , Mercury , Nanoparticles , Mice , Animals , Antioxidants/pharmacology , Antioxidants/metabolism , Mercuric Chloride/toxicity , Toll-Like Receptor 4/metabolism , Brain/metabolism , Oxidative Stress , Polylactic Acid-Polyglycolic Acid Copolymer/pharmacology , Mercury/metabolism , Mercury/pharmacology , Brain Injuries/chemically induced , Brain Injuries/drug therapy , Brain Injuries/prevention & controlABSTRACT
We have adapted a semiautomated method for tracking Caenorhabditis elegans spontaneous locomotor activity into a quantifiable assay by developing a sophisticated method for analyzing the time course of measured activity. The 16-h worm Adult Activity Test (wAAT) can be used to measure C. elegans activity levels for efficient screening for pharmacological and toxicity-induced effects. As with any apical endpoint assay, the wAAT is mode of action agnostic, allowing for detection of effects from a broad spectrum of response pathways. With caffeine as a model mild stimulant, the wAAT showed transient hyperactivity followed by reversion to baseline. Mercury chloride (HgCl2 ) produced an early dose-response hyperactivity phase followed by pronounced hypoactivity, a behavior pattern we have termed a toxicant "escape response." Methylmercury chloride (meHgCl) produced a similar pattern to HgCl2 , but at much lower concentrations, a weaker hyperactivity response, and more pronounced hypoactivity. Sodium arsenite (NaAsO2 ) and dimethylarsinic acid (DMA) induced hypoactivity at high concentrations. Acute toxicity, as measured by hypoactivity in C. elegans adults, was ranked: meHgCl > HgCl2 > NaAsO2 = DMA. Caffeine was not toxic with the wAAT at tested concentrations. Methods for conducting the wAAT are described, along with instructions for preparing C. elegans Habitation Medium, a liquid nutrient medium that allows for developmental timing equivalent to that found with C. elegans grown on agar with OP50 Escherichia coli feeder cultures. A de novo mathematical parametric model for adult C. elegans activity and the application of this model in ranking exposure toxicity are presented.
Subject(s)
Caenorhabditis elegans , Models, Theoretical , Animals , Mercuric Chloride/toxicity , Escherichia coliABSTRACT
The widespread presence of mercury, a heavy metal found in the environment and used in numerous industries and domestic, raises concerns about its potential impact on human health. Nevertheless, the adverse effects of this environmental toxicant at low concentrations are often underestimated. There are emerging studies showing that accumulation of mercury in the eye may contribute to visual impairment and a comorbidity between autism spectrum disorders (ASD) trait and visual impairment. However, the underlying mechanism of visual impairment in humans and rodents is challenging. In response to this issue, zebrafish larvae with a cone-dominated retinal visual system were exposed to 100 nM mercury chloride (HgCl2), according to our previous study, followed by light-dark stimulation, a social assay, and color preference to examine the functionality of the visual system in relation to ASD-like behavior. Exposure of embryos to HgCl2 from gastrulation to hatching increased locomotor activity in the dark, reduced shoaling and exploratory behavior, and impaired color preference. Defects in microridges as the first barrier may serve as primary tools for HgCl2 toxicity affecting vision. Depletion of polyunsaturated fatty acids (PUFAs), linoleic acid, arachidonic acid (ARA), alpha-linoleic acid, docosahexaenoic acid (DHA), stearic acid, L-phenylalanine, isoleucine, L-lysine, and N-acetylputrescine, along with the increase of gamma-aminobutyric acid (GABA), sphingosine-1-phosphate, and citrulline assayed by liquid chromatography-mass spectrometry (LC-MS) suggest that these metabolites serve as biomarkers of retinal impairments that affect vision and behavior. Although suppression of adsl, shank3a, tsc1b, and nrxn1a gene expression was observed, among these tsc1b showed more positive correlation with ASD. Collectively, these results contribute new insights into the possible mechanism of mercury toxicity give rise to visual, cognitive, and social deficits in zebrafish.
Subject(s)
Mercury , Zebrafish , Humans , Animals , Zebrafish/metabolism , Mercury/toxicity , Mercuric Chloride/toxicity , Vision Disorders , Gene ExpressionABSTRACT
Mercury chloride can cause severe liver injury, which involves multiple mechanisms. Ferroptosis plays an important role in regulating the development and progression of liver pathology. Oleanolic acid (OA), a triterpenoid compound widely exists in fruits, has liver protective properties. In this study, we investigated the role of ferroptosis in mercury chloride-induced liver injury and the intervention effect of OA, and clarified the potential mechanism. We found that mercury chloride-induced oxidative stress in liver tissues and cells, leading to lipid peroxidation and iron overload, thereby reducing the expression levels of GPX4 and SLC7A11, and increasing the expression level of TRF1, OA pretreatment improved the changes of GPX4, SLC7A11 and TRF1 induced by mercury chloride, which were related to its inhibition of oxidative stress. Furthermore, We pretreated cells with OA, VC, and Fer-1, respectively and found that VC pretreatment reduced oxidative stress and significantly reversed the gene and protein expressions of GPX4, SLC7A11, and TRF1 in mercury chloride-exposed cells (P < 0.05, vs. HgCl2 group), however, the protein expression level of GPX4 in OA pre-treatment group was lower than that in VC pre-treatment group (P < 0.05). Fer-1 pretreatment decreased the level of iron ions in cells, increased the gene and protein expression levels of GPX4 and SLC7A11, and decreased the gene and protein expression levels of TRF1 (P < 0.05, vs. HgCl2 group), however, the protein expression levels of GPX4 and SLC7A11 in OA pre-treatment group were lower than those in Fer-1 pre-treatment group (P < 0.05). Moreover, vivo experiments also demonstrated that pre-treatment with OA, VC, and Fer-1 reversed the changes in gene expression levels of Nrf2 and SOD1, and protein expression of GPX4 induced by mercury chloride (P < 0.05, vs. HgCl2 group), meanwhile, the difference was not statistically significant among OA, VC, and Fer-1 pretreatment. The improvement effect of OA pretreatment on the change in TFR1 protein expression caused by mercury chloride was similar to that of Fer-1 and VC, however, the intervention effect of OA on SLC7A11 protein expression was not as good as Fer-1 and VC pre-treatment. To sum up, all these results suggest that ferroptosis is involved in mercury chloride-induced liver injury, OA pretreatment alleviated mercury chloride-induced ferroptosis by inhibiting ROS production and iron ion overload, and then alleviate the liver injury.
Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Ferroptosis , Iron Overload , Mercury , Oleanolic Acid , Humans , Chlorides , Mercuric Chloride/toxicity , Oleanolic Acid/pharmacology , Oleanolic Acid/therapeutic use , Reactive Oxygen Species , Iron Overload/drug therapy , Iron , Halogens , Mercury/toxicityABSTRACT
Acute kidney injury, which is associated with high levels of morbidity and mortality, affects a significant number of individuals, and can be triggered by multiple factors, such as medications, exposure to toxic chemicals or other substances, disease, and trauma. Because the kidney is a critical organ, understanding and identifying early cellular or gene-level changes can provide a foundation for designing medical interventions. In our earlier work, we identified gene modules anchored to histopathology phenotypes associated with toxicant-induced liver and kidney injuries. Here, using in vivo and in vitro experiments, we assessed and validated these kidney injury-associated modules by analyzing gene expression data from the kidneys of male Hartley guinea pigs exposed to mercuric chloride. Using plasma creatinine levels and cell-viability assays as measures of the extent of renal dysfunction under in vivo and in vitro conditions, we performed an initial range-finding study to identify the appropriate doses and exposure times associated with mild and severe kidney injuries. We then monitored changes in kidney gene expression at the selected doses and time points post-toxicant exposure to characterize the mechanisms of kidney injury. Our injury module-based analysis revealed a dose-dependent activation of several phenotypic cellular processes associated with dilatation, necrosis, and fibrogenesis that were common across the experimental platforms and indicative of processes that initiate kidney damage. Furthermore, a comparison of activated injury modules between guinea pigs and rats indicated a strong correlation between the modules, highlighting their potential for cross-species translational studies.
Subject(s)
Acute Kidney Injury , Mercuric Chloride , Rats , Male , Guinea Pigs , Animals , Mercuric Chloride/toxicity , Kidney/metabolism , Kidney Function Tests , Acute Kidney Injury/metabolism , Liver/metabolismABSTRACT
Results obtained from rat studies indicate that, even at low concentrations, mercurial species cause harmful effects on the kidneys, by inducing the nephrotic oxidative stress response. In the present work, Hg-associated proteins were identified as possible mercury-exposure biomarkers in rat kidneys exposed to low mercury chloride concentrations for 30 days (Hg-30) and 60 days (Hg-60), using metalloproteomic strategies. The renal proteomic profile was fractioned by two-dimensional electrophoresis and the mercury determinations in kidney samples, protein pellets and protein spots were performed using graphite furnace atomic absorption spectrometry. The characterization of Hg-associated protein spots and the analysis of differentially expressed proteins were performed by liquid chromatography, coupled with tandem mass spectrometry. Eleven Hg-associated protein spots with a concentration range of 79 ± 1 to 750 ± 9 mg kg-1 in the Hg-60 group were identified. The characterization and expression analyses allowed the identification of 53 proteins that were expressed only in the Hg-60 group, 13 "upregulated" proteins (p > 0.95) and 47 "downregulated" proteins (p < 0.05). Actin isoforms and hemoglobin subunits were identified in protein spots of the Hg-60 group, with mercury concentrations in the range of 138 to 750 mg kg-1, which qualifies these proteins as potential mercury-exposure biomarkers.
Subject(s)
Acid-Base Imbalance , Mercury , Animals , Rats , Carrier Proteins , Chlorides , Proteomics , Mercuric Chloride/toxicity , Mercury/toxicity , BiomarkersABSTRACT
In the present investigation, the effect of mercuric chloride on gestation and lactation periods in mice was studied. The animals were treated with 10 ppm of HgCl2 and its complications were evaluated by supplementing 150 and 300 ppm of curcumin, respectively. Results indicated that HgCl2 increased depression-like behavior in treated animals compared to control and effects of depression in offspring significantly (pË0.001) enhanced. Interestingly, the Tail suspension test clearly confirmed that the administration of curcumin enhanced the immobility (pË0.001). The results confirmed that the curcumin administered mice spent less time in the closed arm (P < 0.001), whereas spent a very long time (P < 0.001) in the open arm. Related to the locomotor behaviors, number of squares crossed, wall rear, rear, and locomotion duration were decreased significantly (P < 0.001) while immobility duration was increased (P < 0.001) significantly compared to control. The anxiety and depression behaviors disorder due to mercuric chloride exposure indicated its availability via placenta or/and milk during lactation. The treatment with curcumin improved anxiety and depression behaviors compared to Hg experimental group.
Subject(s)
Curcumin , Mercuric Chloride , Animals , Anxiety/chemically induced , Anxiety/drug therapy , Behavior, Animal , Curcumin/pharmacology , Curcumin/therapeutic use , Depression/chemically induced , Depression/drug therapy , Female , Lactation , Mercuric Chloride/toxicity , Mice , PregnancyABSTRACT
Mercury as a toxic heavy metal will accumulate in the body and induce various diseases through the food chain. However, it is unknown that the detailed mechanism of reproductive disorder induced by inorganic mercury in male mice to date. This study investigated the toxicological effect of mercuric chloride (HgCl2 ) exposure on reproductive system in male mice. Male Kunming mice received normal saline daily or HgCl2 (3 mg/kg bodyweight) by intraperitoneal injection for a week. The reproductive function was evaluated, and the HgCl2 exposure induced the decline of sperm quality, pregnancy rate, mean litter size, and survival rate. Notably, we firstly found the HgCl2 -induced immunosuppression and fibrosis in mice testis according to the results of RNA sequencing. Collectively, these findings demonstrate that HgCl2 exposure disrupts the reproductive system and induces testicular immunosuppression and fibrosis via inhibition of the CD74 signaling pathway in male mice.
Subject(s)
Mercury , Testis , Animals , Animals, Outbred Strains , Fibrosis , Immunosuppression Therapy , Male , Mercuric Chloride/toxicity , Mice , Oxidative StressABSTRACT
Mercury (Hg) is a persistent environmental and industrial pollutant that accumulated in the body and induces oxidative stress and inflammation damage. Selenium (Se) has been reported to antagonize immune organs damage caused by heavy metals. Here, we aimed to investigate the prevent effect of Se on mercuric chloride (HgCl2 )-induced thymus and bursa of Fabricius (BF) damage in chickens. The results showed that HgCl2 caused immunosuppression by reducing the relative weight, cortical area of the thymus and BF, and the number of peripheral blood lymphocytes. Meanwhile, HgCl2 induced oxidative stress and imbalance in cytokines expression in the thymus and BF. Further, we found that thioredoxin-interacting protein (TXNIP) and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome mediated HgCl2 -induced oxidative stress and inflammation. Mechanically, the targeting and inhibitory effect of microRNA (miR)-135b/183 on forkhead box O1 (FOXO1) were an upstream event for HgCl2 -activated TXNIP/NLRP3 inflammasome pathway. Most importantly, Se effectively attenuated the aforementioned damage in the thymus and BF caused by HgCl2 and inhibited the TXNIP/NLRP3 inflammasome pathway by reversing the expression of FOXO1 through inhibiting miR-135b/183. In conclusion, the miR-135b/183-FOXO1/TXNIP/NLRP3 inflammasome axis might be a novel mechanism for Se to antagonize HgCl2 -induced oxidative stress and inflammation in the central immune organs of chickens.
Subject(s)
MicroRNAs , Selenium , Animals , Chickens/metabolism , Inflammasomes/metabolism , Mercuric Chloride/toxicity , MicroRNAs/genetics , MicroRNAs/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Selenium/pharmacologyABSTRACT
The present study was undertaken to investigate the adverse effects of mercuric chloride (HgCl2 ) overload in the fish Channa punctatus. Two sublethal test concentrations of HgCl2 (1/20th and 1/10th of 96 h LC50 i.e., 0.03 mg l-1 (low concentration) and 0.07 mg l-1 (high concentration), respectively, were used for exposure. Blood, liver and kidney tissues of the control and exposed specimens were sampled at intervals of 15, 30, and 45 days to assess alterations in oxidative stress, genotoxicity haematological parameters and histopathology. Significant changes in Hb%, RBC count, WBC count, antioxidant enzyme activity, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione reductase (GR), were recorded. Micronuclei (MN) induction, nuclear abnormalities (NAs) and histopathological alterations were also observed in the exposed fish. Significant (P < 0.05) increase in the activities of SOD, CAT, GSH and GR was observed. After 45 days, a decrease in the level of GSH and GR was noticed which suggests an undermined anti-oxidative defence system in the fish exposed to HgCl2 . Histological examination of the liver and kidney showed serious tissue injury and histological alterations. Significant increases in MN and NA frequencies reveal the DNA damage in erythrocytes of fish, and haematological changes show the toxicological potential of HgCl2 . The observed changes in the antioxidant defence system, genotoxicity and haematological and histological changes in the present study provide the most extensive insight into HgCl2 stress in C. punctatus.
Subject(s)
Antioxidants , Mercuric Chloride , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , DNA Damage , Fishes/genetics , Glutathione/genetics , Glutathione/metabolism , Glutathione/pharmacology , Lipid Peroxidation , Mercuric Chloride/toxicity , Oxidative Stress/genetics , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , Superoxide Dismutase/pharmacologyABSTRACT
Autophagy and apoptosis are two important regulatory mechanisms for how the body can respond to diseases. This study was designed to investigate the protective actions of vitamin E (Vit-E) and lactobacillus plantarum (Lac-B) against mercuric chloride (HgCl2)-induced kidney injury. Thirty albino rats were divided into five groups: group 1 served as the normal group; rats in group 2 received high doses of HgCl2; rats in groups 3, 4 and 5 were given Vit-E, Lac-B and the combination of Vit-E and Lac-B, respectively along with HgCl2 for two weeks. HgCl2 provoked renal injury, manifested by elevation in serum urea, urea nitrogen and creatinine. Kidney levels of oxidative stress and inflammation were markedly increased post HgCl2 administration. Moreover, HgCl2 significantly elevated the gene expression levels of VCAM-1 and cystatin C, while podocin was downregulated. Additionally, it markedly decreased the protein expression of Beclin-1 and Bcl-2. Histopathological examination revealed massive degeneration with congested blood vessels following HgCl2 administration. Treatment with Vit-E or/and Lac-B restored the normal levels of the previously mentioned parameters, as well as improved the morphology of kidney tissues. Both Vit-E and Lac-B provided a protective effect against HgCl2-induced kidney damage by regulating autophagy and apoptosis.
Subject(s)
Lactobacillus plantarum , Vitamin E , Rats , Antioxidants/pharmacology , Apoptosis , Autophagy , Beclin-1/metabolism , Kidney/metabolism , Lactobacillus plantarum/metabolism , Mercuric Chloride/toxicity , Oxidative Stress , Urea/pharmacology , Vitamin E/pharmacology , Vitamin E/metabolism , AnimalsABSTRACT
Objective: To explore the expulsion effect of sodium dimercaptopropanesulfonate (DMPS) on mercury in different organs of mercury poisoning and the therapeutic effect of glutathione (GSH) combined with antioxidant therapy on mercury poisoning. Methods: In February 2019, 50 SPF male SD rats were randomly divided into 5 groups, 10 rats in each group: A (saline negative control group) , B (HgCL2 positive control group) , treatment group (C: intramuscular injection of DMPS 15 mg/kg treatment, D: intramuscular injection of DMPS30 mg/kg treatment, E: intramuscular injection of DMPS 15 mg/kg and intraperitoneal injection of GSH200 mg/kg treatment) . Rats in group B, C, D and E were subcutaneously injected with mercury chloride solution (1 mg/kg) to establish a rat model of subacute mercury poisoning kidney injury. Rats in group A were subcutaneously injected with normal saline. After the establishment of the model, rats in the treatment group were injected with DMPS and GSH. Rats in group A and group B were injected with normal saline. At 21 d (treatment 7 d) and 28 d (treatment 14 d) after exposure, urine and blood samples of 5 rats in each group were collected. Blood biochemistry, urine mercury, urine microalbumin and mercury content in renal cortex, cerebral cortex and cerebellum were detected. Results: After exposure to mercury, the contents of mercury in renal cortex, cerebrum and cerebellum of rats in group B, C, D and E increased, and urine microalbumin increased. Pathology showed renal tubular injury and renal interstitial inflammation. Compared with group B, urinary mercury and renal cortex mercury in group C, D and E decreased rapidly after DMPS treatment, and there was no significant decrease in mercury levels in cerebellum and cerebral cortex of rats, accompanied by transient increase in urinary albumin after DMPS treatment (P<0.05) ; the renal interstitial inflammation in group E was improved after GSH treatment. There was a positive correlation between urinary mercury and the contents of mercury in renal cortex, cerebral cortex and cerebellum (r=0.61, 0.47, 0.48, P<0.05) . Conclusion: DMPS mercury expulsion treatment can significantly reduce the level of metal mercury in the kidney, and there is no significant change in the level of metal mercury in the cortex and cerebellum.
Subject(s)
Kidney Diseases , Mercury Poisoning , Mercury , Animals , Brain/drug effects , Glutathione , Inflammation , Kidney/drug effects , Kidney Diseases/chemically induced , Male , Mercuric Chloride/pharmacology , Mercuric Chloride/therapeutic use , Mercury/urine , Mercury Poisoning/drug therapy , Rats , Rats, Sprague-Dawley , Saline Solution/pharmacology , Saline Solution/therapeutic use , Unithiol/pharmacology , Unithiol/therapeutic useABSTRACT
Exposure to heavy metals may have toxic effects on several human organs causing morbidity and mortality. Metals may trigger or exacerbate autoimmunity in humans. Inbred mouse strains with certain H-2 haplotypes are susceptible to xenobiotic-induced autoimmunity; and their immune response to metals such as mercury, gold, and silver have been explored. Serum antinuclear antibodies (ANA), polyclonal B-cell activation, hypergammaglobulinemia and tissue immune complex deposition are the main features of metal-induced autoimmunity in inbred mice. However, inbred mouse strains do not represent the genetic heterogeneity in humans. In this study, outbred Swiss Webster (SW) mice exposed to gold or mercury salts showed immune and autoimmune responses. Intramuscular injection of 22.5 mg/kg.bw aurothiomalate (AuTM) induced IgG ANA in SW mice starting after 5 weeks that persisted until week 15 although with a lower intensity. This was accompanied by elevated serum levels of total IgG antibodies against chromatin and total histones. Exposure to gold led to development of serum IgG autoantibodies corresponding to H1 and H2A histones, and dsDNA. Both gold and mercury induced polyclonal B-cell activation. Eight mg/L mercuric chloride (HgCl2) in drinking water, caused IgG antinucleolar antibodies (ANoA) after 5 weeks in SW mice accompanied by immune complex deposition in kidneys and spleen. Serum IgG antibodies corresponding to anti-fibrillarin, and anti-PM/Scl-100 antibodies, were observed in mercury-exposed SW mice. Gold and mercury trigger systemic autoimmune response in genetically heterogeneous outbred SW mice and suggest them as an appropriate model to study xenobiotic-induced autoimmunity.
Subject(s)
Antibodies, Antinuclear/blood , Autoimmunity/drug effects , B-Lymphocytes/drug effects , Gold Sodium Thiomalate/toxicity , Immunoglobulin G/blood , Lymphocyte Activation/drug effects , Mercuric Chloride/toxicity , Administration, Oral , Animals , Antigen-Antibody Complex , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Chromatin/immunology , Chromosomal Proteins, Non-Histone/immunology , Exoribonucleases/immunology , Exosome Multienzyme Ribonuclease Complex/immunology , Female , Gold Sodium Thiomalate/administration & dosage , Histones/immunology , Injections, Intramuscular , Kidney/drug effects , Kidney/immunology , Mercuric Chloride/administration & dosage , Mice , Spleen/drug effects , Spleen/immunologyABSTRACT
Cardiovascular diseases are among the main causes of mortality in the world. There is evidence of cardiovascular harm after exposure to low lead or mercury concentrations, but the effects of chronic exposure to the association of low doses of these toxic metals are still unknown. This work evaluated after 4 weeks, the association effects of low concentrations of lead and mercury on blood pressure and vascular resistance reactivity. Wistar rats were exposed for 28 days to lead acetate (1st dose of 4 µg/100 g and subsequent doses of 0.05 µg /100 g/day to cover daily losses) and mercury chloride (1st dose of 2.17 µg/kg and subsequent doses of 0.03 µg/kg/ day to cover daily losses) and the control group received saline, i.m. Results showed that treatment increased blood pressure and induced left ventricular hypertrophy. The mesenteric vascular reactivity to phenylephrine and the endothelium-dependent vasodilator response assessed by acetylcholine did not change. Additionally, reduced involvement of vasoconstrictor prostanoids derived from cyclooxygenase was observed in the PbHg group. By other regulatory routes, such as potassium channels, the vessel showed a greater participation of BKCa channels, and a reduction in the participation of Kv channels and SKCa channels. The endothelium-independent smooth muscle relaxation was significantly impaired by reducing cGMP, possibly through the hyperstimulation of Phosphodiesterase-5 (PDE5). Our results suggested that exposure to low doses of lead and mercury triggers this compensatory mechanism, in response to the augment of arterial pressure.
Subject(s)
Arterial Pressure/drug effects , Cyclic GMP/metabolism , Mercuric Chloride/toxicity , Muscle, Smooth, Vascular/drug effects , Organometallic Compounds/toxicity , Vasodilation/drug effects , Animals , Cyclic Nucleotide Phosphodiesterases, Type 5/metabolism , Down-Regulation , Hypertension/chemically induced , Hypertension/metabolism , Hypertension/physiopathology , Hypertrophy, Left Ventricular/chemically induced , Hypertrophy, Left Ventricular/metabolism , Hypertrophy, Left Ventricular/physiopathology , Mesenteric Arteries/drug effects , Mesenteric Arteries/metabolism , Mesenteric Arteries/physiopathology , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/physiopathology , Rats, Wistar , Second Messenger Systems , Time Factors , Vascular Resistance/drug effectsABSTRACT
INTRODUCTION: The presence of mercury in the environment is a worldwide concern. Inorganic mercury is present in industrial materials, is employed in medical devices, is widely used in batteries, is a component of fluorescent light bulbs, and it has been associated with human poisoning in gold mining areas. The nephrotoxicity induced by inorganic mercury is a relevant health problem mainly in developing countries. The primary mechanism of mercury toxicity is oxidative stress. Trimetazidine (TMZ) is an anti-ischemic drug, which inhibits cellular oxidative stress, eliminates oxygen-free radicals, and improves lipid metabolism. The aim of this study was to evaluate whether the administration of TMZ protects against mercuric chloride (HgCl2) kidney damage. METHODS: Adult male Wistar rats received only HgCl2 (4 mg/kg bw, sc) (Hg group, n = 5) or TMZ (3 mg/kg bw, ip) 30 min before HgCl2 administration (4 mg/kg bw, sc) (TMZHg group, n = 7). Simultaneously, a control group of rats (n = 4) was studied. After 4 days of HgCl2 injection, urinary flow, urea and creatinine (Cr) plasma levels, Cr clearance, urinary glucose, and sodium-dicarboxylate cotransporter 1 (NaDC1) in urine were determined. Lipid peroxidation (MDA) and glutathione (GSH) levels were measured in kidney homogenates. RESULTS: Rats only treated with HgCl2 showed an increase in urea and Cr plasma levels, urinary flow, fractional excretion of water, glucosuria, and NaDC1 urinary excretion as compared with the control group and a decrease in Cr clearance. TMZHg group showed a decrease in urea and Cr plasma levels, urinary flow, fractional excretion of water, glucosuria, NaDC1 urinary excretion, and an increase in Cr clearance when compared to the Hg group. Moreover, MDA and GSH levels observed in Hg groups were decreased and increased, respectively, by TMZ pretreatment. CONCLUSION: TMZ exerted a renoprotective action against HgCl2-induced renal injury, which might be mediated by the reduction of oxidative stress. Considering the absence of toxicity of TMZ, its clinical application against oxidative damage due to HgCl2-induced renal injury should be considered. The fact that TMZ is commercially available should simplify and accelerate the translation of the present data "from bench to bedside." In this context, TMZ become an interesting new example of drug repurposing.
Subject(s)
Kidney Diseases/prevention & control , Mercury Poisoning/prevention & control , Protective Agents/pharmacology , Trimetazidine/pharmacology , Animals , Creatinine/blood , Dicarboxylic Acid Transporters/urine , Glutathione/metabolism , Glycosuria/chemically induced , Glycosuria/prevention & control , Kidney Diseases/chemically induced , Lipid Peroxidation/drug effects , Male , Malondialdehyde/metabolism , Mercuric Chloride/adverse effects , Organic Anion Transporters, Sodium-Dependent/urine , Oxidative Stress/drug effects , Protective Agents/therapeutic use , Rats, Wistar , Sodium Chloride/urine , Symporters/urine , Trimetazidine/therapeutic use , Urea/blood , Urination/drug effectsABSTRACT
C-phycoerythrin (C-PE) is a phycobiliprotein that prevents oxidative stress and cell damage. The aim of this study was to evaluate whether C-PE also counteracts endoplasmic reticulum (ER) stress as a mechanism contributing to its nephroprotective activity. After C-PE was purified from Phormidium persicinum by using size exclusion chromatography, it was characterized by spectrometry and fluorometry. A mouse model of HgCl2-induced acute kidney injury (AKI) was used to assess the effect of C-PE treatment (at 25, 50, or 100 mg/kg of body weight) on oxidative stress, the redox environment, and renal damage. ER stress was examined with the same model and C-PE treatment at 100 mg/kg. C-PE diminished oxidative stress and cell damage in a dose-dependent manner by impeding the decrease in expression of nephrin and podocin normally caused by mercury intoxication. It reduced ER stress by preventing the activation of the inositol-requiring enzyme-1α (IRE1α) pathway and avoiding caspase-mediated cell death, while leaving the expression of protein kinase RNA-like ER kinase (PERK) and activating transcription factor 6α (ATF6α) pathways unmodified. Hence, C-PE exhibited a nephroprotective effect on HgCl2-induced AKI by reducing oxidative stress and ER stress.