Recombinant human metallothionein-III alleviates oxidative damage induced by copper and cadmium in Caenorhabditis elegans.

Recombinant human metallothionein III (rh-MT-III) is a genetically engineered product produced by Escherichia coli fermentation technology. Its molecules contain abundant reducing sulfhydryl groups, which possess the ability to bind heavy metal ions. The present study was to evaluate the binding effects of rh-MT-III against copper and cadmium in vitro and to investigate the antioxidant activity of rh-MT-III using Caenorhabditis elegans in vivo. For in vitro experiments, the binding rates of copper and cadmium were 91.4% and 97.3% for rh-MT-III at a dosage of 200 µg/mL at 10 h, respectively. For in vivo assays, the oxidative stress induced by copper (CuSO4 , 10 µg/mL) and cadmium (CdCl2 , 10 µg/mL) was significantly reduced after 72 h of exposure to different doses of rh-MT-III (5-500 µg/mL), indicated by restoring locomotion behavior and growth, and reducing malondialdehyde and reactive oxygen species levels in C. elegans. Moreover, rh-MT-III decreased the deposition of lipofuscin and fat content, which could delay the progression of aging. In addition, rh-MT-III (500 µg/mL) promoted the up-regulation of Mtl-1 and Mtl-2 gene expression in C. elegans, which could enhance the resistance to oxidative stress by increasing the enzymatic activity of antioxidant defense system and scavenging free radicals. The results indicated that supplemental rh-MT-III could effectively protect C. elegans from heavy metal stress, providing an experimental basis for the future application and development of rh-MT-III.

Clinical and biochemical understanding of Zinc interaction during liver diseases: A paradigm shift.

Zinc (Zn) is an essential and the second most abundant trace element after Iron. It can apply antioxidant, anti-inflammatory, and anti-apoptotic activity. It is assumed to be indispensable for cell division, cellular differentiation and cell signalling. Zinc is essential for proper liver function which is also the site of its metabolism. Depleted Zn concentrations have been observed in both acute and chronic hepatic diseases. It is reported that Zn deficiency or abnormal Zn metabolism during majority of liver diseases is attributed to deficient dietary intake of Zn, augmented disposal of Zn in the urine, activation of certain Zn transporters, and expression of hepatic metallothionein. Undoubtedly, Zn is involved in generating many diseases but how and whether it plays role from acute to fulminant stage of all chronic liver diseases remains to be cleared. Here, we will discuss the role of Zn in development of different diseases specifically the involvement of Zn to understand the aetiology and intricate mechanism of dynamic liver diseases.

CUP1 Metallothionein from Healthy Saccharomyces cerevisiae Colocalizes to the Cytosol and Mitochondrial Intermembrane Space.

Liquid chromatography, mass spectrometry, and metal analyses of cytosol and mitochondrial filtrates from healthy copper-replete Saccharomyces cerevisiae cells revealed that metallothionein CUP1 was a notable copper-containing species in both compartments, with its abundance dependent upon the level of copper supplementation in the growth media. Electrospray ionization mass spectrometry of cytosol and soluble mitochondrial filtrates displayed a full isotopologue pattern of CUP1 in which the first eight amino acid residues were truncated and eight copper ions were bound. Neither apo-CUP1 nor intermediate copper-bound forms were detected, but chelator treatment could generate apo-CUP1. Mitoplasting revealed that mitochondrial CUP1 was located in the intermembrane space. Fluorescence microscopy demonstrated that 34 kDa CUP1-GFP entered the organelle, discounting the possibility that 7 kDa CUP1 enters folded and metalated through outer membrane pores. How CUP1 enters mitochondria remains unclear, as does its role within the organelle. Although speculative, mitochondrial CUP1 may limit the concentrations of low-molecular-mass copper complexes in the organelle.

Central and Enteric Neuroprotective Effects by Eucommia ulmoides Extracts on Neurodegeneration in Rotenone-induced Parkinsonian Mouse.

Parkinson's disease (PD) is a progressive neurodegenerative disease of both the central and peripheral / enteric nervous systems. Oxidative stress and neuroinflammation are associated with the pathogenesis of PD, suggesting that anti-oxidative and anti-inflammatory compounds could be neuroprotective agents for PD. Eucommia ulmoides (EU) is a traditional herbal medicine which exerts neuroprotective effects by anti-inflammatory and anti-oxidative properties. Our previous study showed that treatment with chlorogenic acid, a component of EU, protected against neurodegeneration in the central and enteric nervous systems in a PD model. In this study, we examined the effects of EU extract (EUE) administration on dopaminergic neurodegeneration, glial response and α-synuclein expression in the substantia nigra pars compacta (SNpc), and intestinal enteric neurodegeneration in low-dose rotenone-induced PD model mice. Daily oral administration of EUE ameliorated dopaminergic neurodegeneration and α-synuclein accumulation in the SNpc. EUE treatment inhibited rotenone-induced decreases in the number of total astrocytes and in those expressing the antioxidant molecule metallothionein. EUE also prevented rotenone-induced microglial activation. Furthermore, EUE treatment exerted protective effects against intestinal neuronal loss in the PD model. These results suggest that EU exerts neuroprotective effects in the central and enteric nervous systems of rotenone-induced parkinsonism mice, in part by glial modification.

Effective and stable adsorptive removal of Cadmium(II) and Lead(II) using selenium nanoparticles modified by microbial SmtA metallothionein.

Metallothionein SmtA-modified selenium nanoparticles (SmtA-SeNPs), efficient adsorbents for Cd(II) and Pb(II), were synthesized in the present work. The ligand, microbial SmtA protein, was synthesized using an engineered strain Escherichia coli, posing the benefits of simplicity, safety, and high production. SmtA-SeNPs were spheres with diameters between 68.1 and 122.4 nm, containing amino, hydroxyl, and sulfhydryl functional groups with negatively charged (pH > 5). SmtA-SeNPs displayed better adsorption performance than dissociative SmtA and SeNPs. The adsorption of Cd(II) and Pb(II) mainly depends on the electrostatic attractions and the metal chelation of abundant functional groups. The maximum adsorption capacity was 506.3 mg/g for Cd(II) and 346.7 mg/g for Pb(II), which were higher than the values of most nanoparticles. In addition, SmtA-SeNPs were immobilized with a membrane filter to produce a SmtA-SeNPs filter, and the percentage removal of Cd(II) and Pb(II) increased from 26.75% to 98.13% for Cd(II) and from 9.95% to 99.20% compared with the blank filter. Moreover, the SmtA-SeNPs filter was regenerated using subacid deionized water, and the filter exhibited a stable removal ratio of Cd(II) and Pb(II) in ten continuous cycles of Cd(II)- or Pb(II)-containing wastewater treatment. The residual amounts of Cd and Pb met national standard levels of wastewater discharge.

Sophisticated expression responses of ZNT1 and MT in response to changes in the expression of ZIPs.

The zinc homeostatic proteins Zn transporter 1 (ZNT1) and metallothionein (MT) function in dampening increases in cytosolic zinc concentrations. Conversely, the expression of ZNT1 and MT is expected to be suppressed during decreases in cytosolic zinc concentrations. Thus, ZNT1/MT homeostatic responses are considered to be essential for maintaining cellular zinc homeostasis because cellular zinc concentrations are readily altered by changes in the expression of several Zrt-/Irt-like proteins (ZIPs) under both physiological and pathological conditions. However, this notion remains to be tested experimentally. Here, we investigated the aforementioned homeostatic process by analyzing ZNT1 and MT protein expression in response to ZIP expression. Overexpression of cell-surface-localized ZIPs, such as ZIP4 and ZIP5, increased the cellular zinc content, which caused an increase in the expression of cell-surface ZNT1 and cytosolic MT in the absence of zinc supplementation in the culture medium. By contrast, elimination of the overexpressed ZIP4 and ZIP5 resulted in decreased expression of ZNT1 but not MT, which suggests that differential regulation of ZNT1 and MT expression at the protein level underlies the homeostatic responses necessary for zinc metabolism under certain conditions. Moreover, increased expression of apically localized ZIP4 facilitated basolateral ZNT1 expression in polarized cells, which indicates that such a coordinated expression mechanism is crucial for vectorial transcellular transport. Our results provide novel insights into the physiological maintenance of cellular zinc homeostasis in response to alterations in cytosolic zinc concentrations caused by changes in the expression of ZIPs.

Effects of selenium treatment on endogenous antioxidant capacity in signal crayfish (Pacifastacus leniusculus).

Selenium is an essential element that plays a role in numerous physiological processes and is critical for the maintenance of a strong endogenous antioxidant system. Previous work by our research group reported that the organophosphate pesticide dimethoate decreased glutathione S-transferase activity (GST) in signal crayfish (Pacifastacus leniusculus) collected from the Boise River (Idaho, USA). The goals of this study were to examine whether: 1) sodium selenite modulated the endogenous antioxidants glutathione (GSH), metallothionein (MT), and glutathione S-transferase (GST), thus suggesting a mechanism of antioxidant activity, 2) dimethoate exposure (pro-oxidant stressor) decreased GST activity in a localized population of signal crayfish collected from the Snake River (Idaho, USA), and 3) investigate whether selenium cotreatment ameliorated the adverse effects of dimethoate on GST activity due to the antioxidant properties associated with selenium. Selenium and dimethoate treatments (and co-treatments) did not modulate GSH or MT concentrations at the doses tested in this study. Furthermore, neither selenium nor dimethoate was factors influencing GST activity, and no interaction was found between the treatments. While our results did not support our predictions, they are suggestive and future studies examining the protective role of selenium in pro-oxidant exposure in this species are warranted. Population-specific responses as well as seasonal variations in endogenous antioxidant expression should be considered in future experiments.

Interference with zinc homeostasis and oxidative stress induction as probable mechanisms for cadmium-induced embryo-toxicity in zebrafish.

The present study was conducted to provide new insights into the mechanisms that may be responsible for cadmium (Cd)-induced toxicity in zebrafish larvae as well as the role of the trace element zinc (Zn) in reversing Cd harmful effects. For this purpose, zebrafish eggs were exposed to Cd or/and Zn for 96 h. The effects on morphological aspect; mortality rate; Cd, Zn, and metallothionein (MT) levels; oxidative stress biomarkers; as well as molecular expression of some genes involved in Zn metabolism (Zn-MT, ZIP10, and ZnT1) and in antioxidant defense system (Cu/Zn-SOD, CAT and GPx) were examined. Our results showed that Cd toxicity was exerted, initially, by an interference with Zn metabolism. Thus, Cd was able to modify the expression of the corresponding genes so as to ensure its intracellular accumulation at the expense of Zn, causing its depletion. An oxidative stress was then generated, representing the second mode of Cd action which resulted in developmental anomalies and subsequently mortality. Interestingly, significant corrections have been noted following Zn supplementation based, essentially, on its ability to interact with the toxic metal. The increases of Zn bioavailability, the improvement of the oxidative status, as well as changes in Zn transporter expression profile are part of the protection mechanisms. The decrease of Cd-induced MTs after Zn supplement, both at the protein and the mRNA level, suggests that the protection provided by Zn is ensured through mechanisms not involving MT expression but which rather depend on the oxidative status.

Hepatotoxic effect of lead and hepatoprotective effect of Hydrilla verticillata on hepatic transcriptional and physiological response in edible fish Labeo rohita.

Lead tops the list of developmental toxicants released by industry into the environment according to Commission for Environmental Corporation. Hydrilla verticillata is an aquatic weed and rich source of variable nutrients and chemical constituents like saponins, vitamins, minerals, antioxidants, amino acids, detoxifying agents, etc. This weed is used in a beneficial way to detoxify lead in fish model. The fish were treated with sublethal concentration of lead to induce liver damage and fed with supplementary feed containing 20% of hydrilla dry powder. The present work revealed that lead accumulation is highly toxic to liver. Lead toxicity increased the expressions of cytochrome P450 1 A (CYP1A) and cytochrome P450 3 A (CYP3A) when compared to control. The metal binding stress proteins, heat shock proteins (Hsp60 & Hsp70) and metallothionein were also upregulated due to lead toxicity. Lead intoxicated fish exhibited reduced δ-aminolevulinic acid dehydratase activity in the blood, leading to reduced red blood cell count and changes in cell morphology. The lead toxicity also decreases the level of liver marker enzymes alanine transaminase, aspartate transaminase in serum. In hydrilla supplemented protective group, there was amelioration of these changes. Administration of supplementary feed to the lead intoxicated protective group significantly decreased the expressions of CYP1A, CYP3A, Hsp60, Hsp70 and metallothionein genes. The red blood cell count in lead intoxicated fish was maintained almost normal due to the protective action of Hydrilla verticillata in the diet. The observed increase in the enzymes, which further confirmed the protective effect of Hydrilla verticillata against lead induced toxicity.

Effects of Zinc Glycinate on Growth Performance, Serum Biochemical Indexes, and Intestinal Morphology of Yellow Feather Broilers.

The purpose of this study was to investigate the effects of zinc glycinate (Gly-Zn) on growth performance, serum biochemical index, intestinal morphology, and hepatic metallothionein (MT) mRNA expression in the liver of yellow feather broilers. A total of 540 18-day-old yellow feather broilers were randomly divided into three groups: control group (basal diet), ZnSO4 group (basal diet plus 60 mg Zn/kg from ZnSO4), and Gly-Zn group (basal diet plus 60 mg Zn/kg from zinc glycinate). Each treatment group had 6 replicates with 30 birds in each replicate. The experiment lasted for 42 days (18 to 59 days of age). The results showed that Gly-Zn supplementation significantly improved the average daily gain (ADG) and average daily feed intake (ADFI) of broilers during 18 to 39 days of age compared with that in the control group (P < 0.05) but not different from the ZnSO4 group. The Gly-Zn group had higher glutathione peroxidase (GSH-Px) (P < 0.05) and lower malondialdehyde (MDA) concentrations than the broilers in the control and ZnSO4 group. It was also observed that zinc content in the tibia of Gly-Zn group broilers was higher than the control and ZnSO4 group (P < 0.05). The results of intestinal morphology parameters showed that the Gly-Zn group significantly increased the villus height in duodenum and jejunum (P < 0.05) and decreased crypt depth in duodenum and ileum compared to the control group. However, there were no significant differences between the Gly-Zn group and ZnSO4 group in duodenum and ileum regarding intestinal morphology parameters. The Gly-Zn group significantly increased mRNA expression of MT in the liver than both control and ZnSO4 groups (P < 0.05). Collectively, the results indicated that supplementing 60 mg Zn/kg through zinc glycinate improved growth performance and serum indexes as well as intestinal morphology of yellow feather broilers. It also regulates MT gene expression more effectively than the ZnSO4 group at the transcriptional level.

Protective Role of the Essential Trace Elements in the Obviation of Cadmium Toxicity: Glimpses of Mechanisms.

Cadmium (Cd) is toxic non-essential heavy metal that precipitates adverse health effects in humans and animals. Chelation therapy, the typical treatment for cadmium toxicity, has certain safety and efficacy issues to treat long term cadmium toxicity, in particular. Recent studies have shown that essential trace elements can play important roles in obviating experimental Cd toxicity. This study organizes and reviews the prototypical evidences of the protective effects of essential trace elements against Cd toxicity in animals and attempts to point out the underlying mechanisms. Zinc, selenium, iron, and combinations thereof are reported to be active. The major mechanisms elucidated inter alia are-induction of metallothionein (MT) synthesis and Cd-MT binding (for zinc), modulation of oxidative stress and apoptosis, interference in cadmium absorption and accumulation from body-thereby maintenance of essential metal homeostasis and cytoprotection. Based on the findings, essential trace elements can be recommended for the susceptible population. The application of these trace elements appears beneficial for both the prevention and remediation of long-term Cd toxicity operative via multiple mechanisms with no or minimal adverse effects as compared to the conventional chelation therapy.

Effects of Zinc Lactate Supplementation on Growth Performance, Intestinal Morphology, Serum Parameters, and Hepatic Metallothionein of Chinese Yellow-Feathered Broilers.

In poultry, organic zinc compounds have higher bioavailability than inorganic zinc sources. However, as an organic zinc source, the application of zinc lactate (ZL) on Chinese yellow-feathered broilers has been rarely reported. Hence, the present study aimed to investigate the effects of ZL supplementation on growth performance, small intestinal morphology, serum biochemical parameters, immune organ index, as well as hepatic metallothionein of Chinese yellow-feathered broilers. A total of 2100 broilers (19 days old) were randomly assigned to 5 treatment groups, including the control (fed basal diet), ZL40 (basal diet plus 40 mg/kg ZL), ZL60 (basal diet plus 60 mg/kg ZL), ZL80 (basal diet plus 80 mg/kg ZL), and ZS80 (basal diet plus 80 mg/kg ZS. Each treatment group had 6 replicates with 70 chickens per replicate. Compared to the control group, the ZL40 and the ZS80 groups had a lower feed to gain ratio (P < 0.05), ZL40 group had higher duodenum and ileum villus heights (P < 0.05), and ZS80 and ZL80 groups had a lower ratio of villus height to crypt depth in the jejunum (P < 0.01). In addition, the ZL60 group had a higher concentration of total protein (P < 0.05) and activity of glutathione peroxidase (GSH-Px) (P < 0.01) compared with the ZS80 and the control groups. Interestingly, the ZL40, ZL60, and ZL80 groups all had higher levels of hepatic metallothionein than the other groups (P < 0.01). In conclusion, zinc lactate had a higher bioavailability and could be used as an alternative to zinc sulfate.

Relative Bioavailability of Broiler Chickens Fed with Zinc Hydroxychloride and Sulfate Sources for Corn-Soybean Meal.

This study was conducted to determine relative bioavailability (RBV) of basic zinc chloride (BZC) compared to zinc sulfate monohydrate (ZSM) for broilers. A randomized design involving a 2 × 3 factorial arrangement of the different treatment regimens plus one negative control was set up for this study. A total of 630 newly hatched male AA broiler chicks were randomly allocated to 42 different pens (15 chickens/pen) and assigned to 7 dietary treatments in a completely randomized design. The diet was supplemented with 0, 20, 40, or 80 mg of Zn mg/kg of feed in the form of ZSM or BZC. The results showed that zinc supplementation altered average daily gain (ADG) and feed conversion ratio (FCR) (P < 0.05) for both zinc sources. It was observed that the weight gain increased linearly (P < 0.01) and FCR decreased linearly as dietary BZC and ZSM concentration increased. Moreover, compared with chickens fed with ZSM, chickens fed with BZC had higher ADG and lower FCR from days 0 to 14 (P < 0.05), and higher activity of plasma alkaline phosphatase (ALP) (P < 0.05), total superoxide dismutase (T-SOD), and CuZn superoxide dismutase (CuZn-SOD) (P < 0.01) in the plasma of chickens fed with BZC at zinc level 80 mg/kg at day 14. The pancreas divalent metal-ion transporter-1 (DMT1) mRNA expression of chickens fed with BZC was found to be significantly enhanced at day 28, and the pancreas metallothionein (MT) mRNA expression for BZC fed group was also markedly increased at Zn levels of 20 and 40 mg/kg respectively. The relative bioavailability (RBV) of BZC (Zn sulfate 100%) based on ADG in the starter phase was 110.82%, whereas the tibia zinc content, as well as the activities of plasma ALP and CuZn-SOD, and the pancreas MT mRNA level were in the range between 108 and 119%. It was thus concluded that BZC was more efficacious than Zn sulfate and could serve as a potentially novel zinc source in the broilers.

Metal-Specificity Divergence between Metallothioneins of Nerita peloronta (Neritimorpha, Gastropoda) Sets the Starting Point for a Novel Chemical MT Classification Proposal.

Metallothioneins' (MTs) biological function has been a matter of debate since their discovery. The importance to categorize these cysteine-rich proteins with high coordinating capacity into a specific group led to numerous classification proposals. We proposed a classification based on their metal-binding abilities, gradually sorting them from those with high selectivity towards Zn/Cd to those that are Cu-specific. However, the study of the NpeMT1 and NpeMT2isoforms of Nerita peloronta, has put a new perspective on this classification. N. peloronta has been chosen as a representative mollusk to elucidate the metal-binding abilities of Neritimorpha MTs, an order without any MTs characterized recently. Both isoforms have been recombinantly synthesized in cultures supplemented with ZnII, CdII, or CuII, and the purified metal-MT complexes have been thoroughly characterized by spectroscopic and spectrometric methods, leading to results that confirmed that Neritimorpha share Cd-selective MTs with Caenogastropoda and Heterobranchia, solving a so far unresolved question. NpeMTs show high coordinating preferences towards divalent metal ions, although one of them (NpeMT1) shares features with the so-called genuine Zn-thioneins, while the other (NpeMT2) exhibits a higher preference for Cd. The dissimilarities between the two isoforms let a window open to a new proposal of chemical MT classification.

MALDI-TOF-MS and XAS analysis of complexes formed by metallothionein with mercury and/or selenium.

Mercury (Hg) is highly toxic while selenium (Se) has been found to antagonize Hg. Both Hg and Se have been found to induce metallothioneins (MTs). In this study, the complexes formed by metallothionein-1 (MT-1) with HgCl2 and/or Na2SeO3 was studied using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and X-ray absorption spectrometry (XAS). MALDI-TOF-MS and XAS indicated the formation of Hg-S bond or Se-S bond when MT-1 reacted with HgCl2 or Na2SeO3, respectively. The bond lengths of Hg-S and coordination number in MT-Hg are 2.41 ± 0.02 Å and 3.10 and in MT-Se are 2.50 ± 0.03 Å and 2.69. A MT-Se-Hg complex was formed when MT-1 reacted with both HgCl2 and Na2SeO3, in which the neighboring atom of Hg is Se, while the neighboring atoms of Se are S and Hg. Our study is an important step towards a better understanding of the interaction of HgCl2 and/or Na2SeO3 with proteins like MT-1.

Dietary supplementation with increasing doses of an organic micromineral complex on juvenile Nile tilapia: Effects on the antioxidant defense system and tissue deposition.

The effect of increasing amounts (0%, 25%, 50%, 75%, and 100%) of dietary supplementation with an organic micromineral complex (Fe, Zn, Cu, Mn, and Se) on antioxidant defenses and mineral deposition in tissues of Nile tilapia juveniles was evaluated, where 100% supplementation represented the average adopted by the feed industry in Brazil. Fish (initial weight 23.93 ± 0.80 g) were fed until apparent satiation twice a day for 56 days. The maximum deposition of Fe and Zn in the hepatopancreas occurred in fish given approximately 50% supplementation, whereas the deposition of Mn and Se increased linearly with the inclusion of the complex. The activity of catalase and superoxide dismutase in the hepatopancreas decreased in fish fed the 50% dose, when compared to those not receiving mineral supplementation or those receiving higher doses. Glutathione peroxidase (GPx) activity in the hepatopancreas increased as the dietary Se concentration increased. However, the concentration of metallothionein in the hepatopancreas showed an inverse relationship to the increase in dietary supplementation of the organic mineral complex. There was no relationship between the doses of organic micromineral supplementation and the activities of GPx, reduced glutathione, non-protein thiols, or protein carbonylation. However, diets supplemented with 50% to 100% promoted greater GPx activity when compared to the 0% supplemented diet. Supplementation with intermediate doses of organic microminerals, approximately 50% of that used in commercial tilapia diets, promoted the homeostasis of metal metabolism, especially for Fe and Zn.

Melatonin-mediated MT2 attenuates colitis induced by dextran sodium sulfate via PI3K/AKT/Nrf2/SIRT1/RORα/NF-κB signaling pathways.

BACKGROUND: Inflammatory bowel disease (IBD) is an inflammatory response relative chronic disease in the intestinal tract. Our previous study demonstrated melatonin exerts an improvement effect on stress related IBD. The present study was further performed to clarify the mechanism of melatonin in dextran sodium sulfate (DSS)-induced colitis in mice. METHODS: We successfully established a DSS-induced colitis mouse model and hydrogen peroxide (H2O2)-treated intestinal epithelial cells (IECs) with or without melatonin supplementation to explore the improvement of melatonin in the DSS-induced colitis. RESULTS: Melatonin supplementation normalized the colitis, oxidative stress, mitochondria dysfunction, apoptosis and inflammation response, including the increase of intestinal permeability, histological score and the level of IL-1ß, TNF-α, iNOS, NLRP3, MDA, Bax, Caspase3, Cytochrome C and Caspase9, as well as the reduction of body weight, colon length, Card9, IFN-γ, IL-10, T-AOC, Calpain1, Mfn2, VDAC1, RORα and SIRT1 proteins in DSS-treated mice. However, the improvement effects of melatonin were blocked by MT2 antagonist 4P-PDOT, PI3K antagonist LY294002, AKT antagonist GSK690693 and Nrf2 antagonist ML385, while mimicked by P65 antagonist PDTC in H2O2-IECs. CONCLUSION: Melatonin-mediated MT2 activated PI3K/AKT/Nrf2/RORα/SIRT1 pathway and suppressed NF-κB pathway, ultimately improved DSS-induced colitis, which provides evidence for melatonin as an efficient therapy against oxidative stress associated IBD.

Health Beneficial Properties of Grapevine Seed Extract and Its Influence on Selected Biochemical Markers in the Blood, Liver and Kidneys of Rattus norvegicus.

Cadmium (Cd) is a heavy metal that occurs in all areas of the environment, including the food chain. In the body, it causes oxidative stress by producing free radicals that are harmful to the cells. Grape seed extract (GSE) contains a wide range of biologically active components that help to neutralize the adverse effects of free radicals. In this study, the effects of GSE prepared form semi-resistant grapevine cultivar Cerason, which is rich in phenolics, on biochemical markers of brown rats exposed to the effects of cadmium were monitored. GSE increased the plasma antioxidant activity and, in the kidneys and the liver, Cd content was significantly lowered by GSE co-administration. Accordingly, the increase in creatinine content and alanine aminotransferase activity and the decrease of catalase and superoxide dismutase activities caused by cadmium were slowed down by GSE co-administration. The results of this work reveal that grape seed extract offers a protective effect against the intake of heavy metals into the organism.

Subacute safety assessment of recombinant Lactococcus lactis on the gut microbiota of male Sprague-Dawley rats.

BACKGROUND: Lactococcus lactis strain pGSMT/MG1363 is a genetically modified microorganism (GMM) that constitutively expresses human metallothionein-I fusion protein to combine with intracellular lead. Unlike traditional probiotics, pGSMT/MG1363 lacks a history of safe use in food. Administration of microorganism could influence the gut microbial community and consequently confer health benefits or cause disadvantages to the host. To date, little has been done to assess the influence of recombinant strain pGSMT/MG1363 on the stability of gut microbiota. RESULTS: Liver, testis and kidney sections of male Sprague-Dawley rats orally administered pGSMT/MG1363 for 6 weeks showed normal structure and no pathological damage. There were no adverse effects on the analyzed serum biochemical parameters between the pGSMT/MG1363 group and the MG1363 group. Principal coordinate analysis showed that, compared with the MG1363 group, the 6-week-old fecal gut microbiota of rats fed with pGSMT/MG1363 was not significantly different (Adonis, P = 0.802). pGSMT/MG1363 treatment for 6 weeks did not significantly change the relative abundance of gut microbiota at the phylum and genus levels in comparison with MG1363 treatment. CONCLUSION: Compared to the non-GM strain MG1363 group, administration of the recombinant strain pGSMT/MG1363 for 6 weeks showed no adverse effects on the analyzed physiological parameters and gut microbial compositions of male Sprague-Dawley rats. The results suggested that, in terms of gut microbiota stability, pGSMT/MG1363 could be considered as safe as MG1363, at least for short-term intake. Further toxicological evaluations still need to be considered before drawing a definite conclusion concerning the safe use of pGSMT/MG1363. © 2021 Society of Chemical Industry.

Nutritive Manganese and Zinc Overdosing in Aging C. elegans Result in a Metallothionein-Mediated Alteration in Metal Homeostasis.

SCOPE: Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration. METHODS AND RESULTS: Chronic co-exposure of C. elegans to Mn and Zn increases metal uptake, exceeding levels of single metal exposures. Supplementation with Mn and/or Zn also leads to an age-dependent increase in metal content, a decline in overall mRNA expression, and metal co-supplementation induced expression of target genes involved in Mn and Zn homeostasis, in particular metallothionein 1 (mtl-1). Studies in transgenic worms reveal that mtl-1 played a prominent role in mediating age- and diet-dependent alterations in metal homeostasis. Metal dyshomeostasis is further induced in parkin-deficient nematodes (Parkinson's disease (PD) model), but this did not accelerate the age-dependent dopaminergic neurodegeneration. CONCLUSIONS: A nutritive overdose of Mn and Zn can alter interactions between essential metals in an aging organism, and metallothionein 1 acts as a potential protective modulator in regulating homeostasis.