Simultaneous induction of Pb-metallothionein-like protein and Zn-thionein in the liver of rats given lead acetate.
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ABSTRACT:
SUBMITTER: Ikebuchi H
PROVIDER: S-EPMC1153059 | biostudies-other | 1986 Jan
REPOSITORIES: biostudies-other
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Project description:Exposure to lead (Pb) causes multiorgan dysfunction including reproductive impairments. Here, we examined the protective effects of coenzyme Q10 (CoQ10) administration on testicular injury induced by lead acetate (PbAc) exposure in rats. This study employed four experimental groups (n = 7) that underwent seven days of treatment as follows: control group intraperitoneally (i.p.) treated with 0.1?ml of 0.9% NaCl containing 1% Tween 80 (v : v), CoQ10 group that was i.p. injected with 10?mg/kg CoQ10, PbAc group that was i.p. treated with PbAc (20?mg/kg), and PbAc+CoQ10 group that was i.p. injected with CoQ10 2?h after PbAc. PbAc injection resulted in increasing residual Pb levels in the testis and reducing testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Additionally, PbAc exposure resulted in significant oxidative damage to the tissues on the testes. PbAc raised the levels of prooxidants (malondialdehyde and nitric oxide) and reduced the amount of endogenous antioxidative proteins (glutathione and its derivative enzymes, catalase, and superoxide dismutase) available in the cell. Moreover, PbAc induced the inflammatory response as evidenced by the upregulation of inflammatory mediators (tumor necrosis factor-alpha and interleukin-1 beta). Further, PbAc treatment induced apoptosis in the testicular cells, as indicated by an increase in Bax and caspase 3 expression, and reduced Bcl2 expression. CoQ10 supplementation improved testicular function by inhibiting Pb accumulation, oxidative stress, inflammation, cell death, and histopathological changes following PbAc exposure. Our findings suggest that CoQ10 can act as a natural therapeutic agent to protect against the reproductive impairments associated with PbAc exposure.
| S-EPMC7290879 | biostudies-literature
Project description:Despite restrictions, exposure to lead (Pb) continues. Moreover, exposure varies and is often higher in lower socioeconomic status (SES) families and remains a significant risk to cognitive development. Stress is another risk factor. Lower SES may be a proxy for stress in humans. When stress and Pb co-occur, risk may be increased. A few previous experiments have combined Pb with intermittent or acute stress but not with chronic stress. To determine if chronic developmental stress affects outcome in combination with Pb, we tested such effects on growth, organ weight, brain monoamines, and response to an acute stressor. Sprague Dawley rats were gavaged with Pb acetate (1 or 10 mg/kg) or vehicle every other day from postnatal day (P)4-29 and reared in standard or barren cages. Subsets were analyzed at different ages (P11, 19, 29). Chronic stress did not alter blood Pb levels but altered HPA axis response during early development whereas Pb did not. Pb treatment and rearing each altered organ-to-body weight ratios, most notably of thymus weights. Both Pb and rearing resulted in age- and region-dependent changes in serotonin and norepinephrine levels and in dopamine and serotonin turnover. The model introduced here may be useful for investigating the interaction of Pb and chronic developmental stress.
| S-EPMC3005021 | biostudies-literature
Project description:Mammalian metallothioneins are redox-active metalloproteins. In the case of zinc metallothioneins, the redox activity resides in the cysteine sulfur ligands of zinc. Oxidation releases zinc, whereas reduction re-generates zinc-binding capacity. Attempts to demonstrate the presence of the apoprotein (thionein) and the oxidized protein (thionin) in tissues posed tremendous analytical challenges. One emerging strategy is differential chemical modification of cysteine residues in the protein. Chemical modification distinguishes three states of the cysteine ligands (reduced, oxidized and metal-bound) based on (i) quenched reactivity of the thiolates when bound to metal ions and restoration of thiol reactivity in the presence of metal-ion-chelating agents, and (ii) modification of free thiols with alkylating agents and subsequent reduction of disulfides to yield reactive thiols. Under normal physiological conditions, metallothionein exists in three states in rat liver and in cell lines. Ras-mediated oncogenic transformation of normal HOSE (human ovarian surface epithelial) cells induces oxidative stress and increases the amount of thionin and the availability of cellular zinc. These experiments support the notion that metallothionein is a dynamic protein in terms of its redox state and metal content and functions at a juncture of redox and zinc metabolism. Thus redox control of zinc availability from this protein establishes multiple methods of zinc-dependent cellular regulation, while the presence of both oxidized and reduced states of the apoprotein suggest that they serve as a redox couple, the generation of which is controlled by metal ion release from metallothionein.
| S-EPMC1863571 | biostudies-other
Project description:The current study was aimed to evaluate the preventive effects of Indigofera oblongifolia leaf extract (IOLE) on lead acetate (PbAc)-induced hepatotoxicity in adult male Wistar rats. PbAc was intraperitoneally injected at a dose of 20 mg/kg body weight for 5 days alone or in combination with the IOLE (100 mg/kg). Liver lead concentration and oxidative stress markers such as lipid peroxidation, hydrogen peroxide, nitric oxide, and glutathione content were investigated in addition to the enzymatic antioxidant activities. PbAc injection caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, hydrogen peroxide, and nitric oxide, with a concomitant decline in the glutathione content compared with the control, accompanied by a significant inhibition of antioxidant enzyme activities. The induction of oxidative stress, lead accumulation, and histological alterations in the liver were successfully minimized by pre-administration of IOLE. In addition, the PbAc group showed increase in the levels of Bax, caspase-3, and matrix metalloproteinase-9 proteins, while the expression of Bcl-2 protein was decreased. Prior administration of IOLE significantly mitigated apoptosis and fibrosis in the liver. Finally, the major components in I. oblongifolia extract were identified as polyphenols, flavonoids, and organic acids using liquid chromatography coupled mass spectroscopy. Thus, the findings of the current study revealed that I. oblongifolia had protective, anti-fibrotic, antioxidant, and anti-apoptotic activities on PbAc-induced hepatotoxicity. The beneficial effects of I. oblongifolia were in part mediated by Nrf2/HO-1 pathway.
| S-EPMC4938219 | biostudies-literature
Project description:A novel bismuth (Bi)-biopolymer (chitosan) nanocomposite screen-printed carbon electrode was developed using a Bi and chitosan co-electrodepositing technique for detecting multiple heavy metal ions. The developed sensor was fabricated with environmentally benign materials and processes. In real wastewater, heavy metal detection was evaluated by the developed sensor using square wave anodic stripping voltammetry (SWASV). The nanocomposite sensor showed the detection limit of 0.1 ppb Zn2+, 0.1 ppb Cd2+ and 0.2 ppb Pb2+ in stock solutions. The improved sensitivity of the Bi-chitosan nanocomposite sensor over previously reported Bi nanocomposite sensors was attributed to the role of chitosan. When used for real wastewater samples collected from a mining site and soil leachate, similar detection limit values with 0.4 ppb Cd2+ and 0.3 ppb Pb2+ were obtained with relative standard deviations (RSD) ranging from 1.3% to 5.6% (n = 8). Temperature changes (4 and 23 °C) showed no significant impact on sensor performance. Although Zn2+ in stock solutions was well measured by the sensor, the interference observed while detecting Zn2+ in the presence of Cu2+ was possibly due to the presence of Cu-Zn intermetallic species in mining wastewater. Overall, the developed sensor has the capability of monitoring multiple heavy metals in contaminated water samples without the need for complicated sample preparation or transportation of samples to a laboratory.
| S-EPMC6723456 | biostudies-other
Project description:Metallothioneins (MTs) are a group of cysteine-rich heavy-metal-binding proteins. We have investigated MT gene expression in the ventral and dorsolateral lobes of the prostate and coagulating gland of male Wistar rats. In intact rats, both MT mRNA and MT were present in the dorsolateral lobe and coagulating gland but not in the ventral lobe. Orchidectomy caused involution of the above organs, and both MT mRNA and MT were considerably decreased or become undetectable. An injection of testosterone propionate into orchidectomized rats restored not only the size of these organs, but also MT mRNA and MT concentrations, particularly in the dorsolateral lobe and coagulating gland. In the dorsolateral lobe, no selective uptake of Zn2+ preceding the increase in MT was observed, suggesting that Zn2+ ions are not associated with the increased expression of the MT gene. The present result suggests that of the male auxiliary genital organs, the dorsolateral lobe and coagulating gland, but not the ventral lobe, contain MT, the biosynthesis of which is regulated by testosterone.
| S-EPMC1217491 | biostudies-other
Project description:A new, sensitive platform for the simultaneous electrochemical assay of Zn(II), Cd(II) and Pb(II) in aqueous solution has been developed. The platform is based on a new bimetallic Hg-Bi/single-walled carbon nanotubes (SWNTs) composite modified glassy carbon electrode (GCE), demonstrating remarkably improved performance for the anodic stripping assay of Zn(II), Cd(II) and Pb(II). The synergistic effect of Hg and Bi as well as the enlarged, activated surface and good electrical conductivity of SWNTs on GCE contribute to the enhanced activity of the proposed electrode. The analytical curves for Zn(II), Cd(II) an Pb(II) cover two linear ranges varying from 0.5 to 11 μg L(-1) and 10 to 130 μg L(-1) with correlation coefficients higher than 0.992. The limits of detection for Zn(II), Cd(II) are lower than 2 μg L(-1) (S/N = 3). For Pb(II), moreover, there is another lower, linear range from 5 to 1100 ng L(-1) with a coefficient of 0.987 and a detection limit of 0.12 ng L(-1). By using the standard addition method, Zn(II), Cd(II) and Pb(II) ions in river samples were successfully determined. These results suggest that the proposed method can be applied as a simple, efficient alternative for the simultaneous monitoring of heavy metals in water samples. In addition, this method demonstrates the powerful application of carbon nanotubes in electrochemical analysis of heavy metals.
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Project description:Determination of Pb-210 (210Pb) in aqueous solution is a common radioanalytical challenge in environmental science. Widely used methods for undertaking these analyses (e.g., ASTM D7535) rely on the use of stable lead (Pb) as a yield tracer that takes into account losses of 210Pb that inevitably occur during elemental/radiochemical separations of the procedures. Although effective, these methods introduce technical challenges that can be difficult to track and potentially introduce uncertainty that can be difficult to quantify. Examples of these challenges include interference from endogenous stable Pb in complex sample matrices; contamination of stable Pb carrier with 210Pb; and high detection limits due to counting efficiency limitations. We hypothesized that many of these challenges could be avoided by the use of the electron-capture, gamma-emitting isotope, 203Pb as a chemical yield tracer in the analysis of 210Pb. A series of experiments were performed to evaluate the efficacy of 203Pb as a tracer. Four different matrices were analyzed, including a complex matrix (hydraulic-fracturing produced fluids); and samples comprising less complicated matrices (i.e., river water, deionized water, and tap water). Separation techniques and counting methodologies were also compared and optimized. Due to a relatively short-half life (52 h), 203Pb tracer is effectively massless for the purposes of chemical separations, allowing for reduced chromatography column resin bed volumes. Because 203Pb is a gamma emitter (279 keV; 81% intensity), recovery can be determined non-destructively in a variety of matrices, including liquid scintillation cocktail. The use of liquid scintillation as a counting methodology allowed for determination of 210Pb activities via 210Pb or 210Po; and recoveries of greater than 90% are routinely achievable using this approach. The improved method for the analysis of 210Pb in aqueous matrices allows for the analysis of complex matrices, at reduced cost, while providing greater counting flexibility in achieving acceptable detections limits.
| S-EPMC6785750 | biostudies-literature
Project description:Lead is a ubiquitous environmental and industrial pollutant. Its nonbiodegradable toxicity induces a plethora of human diseases. The current study was undertaken to purify a novel 252-kDa bioactive glycoprotein containing 1.15% carbohydrate from the edible fungus Auricularia polytricha with the ability of adsorbing lead and producing detoxification. The A. polytricha detoxifying glycoprotein (APL), which displayed unique molecular properties, was purified by ion exchange chromatography and gel filtration chromatography. For investigating the protective effects of A. polytricha, Sprague Dawley (SD) rats were divided into six groups which received daily intraperitoneal injection of lead acetate for 30 days, followed by gavage with APL (40, 80, 160 mg/kg B body weight) and EDTA (300 mg/kg body weight) for 30 days after successful establishment of an animal model of lead detoxification. The serum concentrations of lead and the liver biomarkers AST and ALT were significantly (p<0.05) improved by APL treatments, as well as treatment with the positive control EDTA. Likewise, results on lead residue showed that the clearance ratios of liver and kidney were respectively 44.5% and 18.1% at the high APL dosage, which was even better than the corresponding data for EDTA. Proteomics disclosed that 351 proteins differentially expressed due to lead exposure and the expression levels of 41 proteins enriched in the pathways mainly involved in cell detoxification and immune regulation were normalized after treatment with APL-H. Our results signify that APL may ameliorate lead-induced hepatorenal injury by positive regulation of immune processing, and suggest that APL be applied as a therapeutic intervention of lead poisoning in clinic treatment. This report represents the first demonstration of the protective action of a novel mushroom protein on lead-elicited hepatorenal toxicity.
2023-04-04 | PXD040493 | Pride
Project description:Cu,Zn-metallothioneins were purified from bovine calf liver in order to examine the stoichiometry of metal binding to the protein. Copper and zinc analyses were carried out by atomic absorption spectrophotometry. Consistent quantitative thiolate analyses were obtained spectrophotometrically with Ellman's reagent and amperometrically with phenylmercuric acetate. These were used to define protein concentration. A complementary method to assess the sum of the thiol and Cu(I) content of metallothionein involved titration of the reducing equivalents of the protein with ferricyanide. The stoichiometry of reaction was consistent with the oxidation of all the sulphydryl groups to disulphides and all of the bound Cu from the cuprous to the cupric oxidation state. Accordingly to these methods, total numbers of zinc plus copper ions bound to metallothionein isolated from a number of calf livers centred on about 7, 10-12, or 15 g-atoms of metal per mol of protein. The reactivity of ferricyanide and 4,7-phenylsulphonyl-2,9-dimethyl-1, 10-phenanthroline (BCS) with Cu,Zn-metallothioneins of various metal ratios was assessed. Zinc metallothionein reacted almost entirely in two slow steps with ferricyanide. As the Cu content of the protein increased, the fraction of reaction occurring in the time of mixing increased in parallel. BCS was able to remove 70-80% of metallothionein-bound Cu as Cu(I). The rest was resistant to reaction.
| S-EPMC1217500 | biostudies-other