Grouping strategies for assessing and managing persistent and mobile substances

Environmental Sciences Europe, Год журнала: 2024, Номер 36(1)

Опубликована: Май 21, 2024

Persistent, mobile and toxic (PMT), or very persistent (vPvM) substances are a wide class of chemicals that recalcitrant to degradation, easily transported, potentially harmful humans the environment. Due their persistence mobility, these often widespread in environment once emitted, particularly water resources, causing increased challenges during treatment processes. Some PMT/vPvM such as GenX perfluorobutane sulfonic acid have been identified high concern (SVHCs) under European Registration, Evaluation, Authorisation Restriction Chemicals (REACH) regulation. With hundreds thousands potential yet be assessed managed, effective efficient approaches avoid case-by-case assessment prevent regrettable substitution necessary achieve Union's zero-pollution goal for non-toxic by 2050. Substance grouping has helped global regulation some highly hazardous chemicals, e.g., through Montreal Protocol Stockholm Convention. This article explores strategies identifying, assessing managing substances. The aim is facilitate early identification lesser-known new meet criteria, prompt additional testing, use substitution, integrate into existing risk management strategies. Thus, this provides an overview reviews definition criteria various lists available. It covers current groups, compares substance hazard regulation, discusses advantages disadvantages then substances, including read-across, structural similarity commonly retained moieties, well application using cheminformatics predict P, M T properties selected examples. Effective can accelerate especially lack information. Advances read-across methods tools needed support chemical management, preventing broad entry market favouring safer more sustainable alternatives.

Язык: Английский

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Melamine-induced adrenal structural and functional alterations and the contribution of morin to the adrenal repair in Wistar rats

Tissue and Cell, Год журнала: 2025, Номер 95, С. 102826 - 102826

Опубликована: Март 1, 2025

Язык: Английский

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Empagliflozin ameliorates diabetic cardiomyopathy probably via activating AMPK/PGC-1α and inhibiting the RhoA/ROCK pathway

World Journal of Diabetes, Год журнала: 2023, Номер 14(12), С. 1862 - 1876

Опубликована: Дек. 14, 2023

BACKGROUND Diabetic cardiomyopathy (DCM) increases the risk of hospitalization for heart failure (HF) and mortality in patients with diabetes mellitus. However, no specific therapy to delay progression DCM has been identified. Mitochondrial dysfunction, oxidative stress, inflammation, calcium handling imbalance play a crucial role pathological processes DCM, ultimately leading cardiomyocyte apoptosis cardiac dysfunctions. Empagliflozin, novel glucose-lowering agent, confirmed reduce HF diabetic patients. Nevertheless, molecular mechanisms by which this agent provides cardioprotection remain unclear. AIM To investigate effects empagliflozin on high glucose (HG)-induced stress underlying mechanism. METHODS Twelve-week-old db/db mice primary cardiomyocytes from neonatal rats stimulated HG (30 mmol/L) were separately employed as vivo vitro models. Echocardiography was used evaluate function. Flow cytometry TdT-mediated dUTP-biotin nick end labeling staining assess myocardial cells. function assessed cellular ATP levels changes mitochondrial membrane potential. Furthermore, intracellular reactive oxygen species production superoxide dismutase activity analyzed. Real-time quantitative PCR analyze Bax Bcl-2 mRNA expression. Western blot analysis measure phosphorylation AMP-activated protein kinase (AMPK) myosin phosphatase target subunit 1 (MYPT1), well peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) active caspase-3 levels. RESULTS In experiment, developed DCM. treatment (10 mg/kg/d) 8 wk substantially enhanced significantly reduced apoptosis, accompanied an increase AMPK PGC-1α levels, decrease MYPT1 heart. findings indicate that μM) or fasudil (FA) (a ROCK inhibitor, 100 overexpression attenuated HG-induced injury, apoptosis. above partly reversed addition compound C (CC). cells exposed HG, increased p-AMPK while decreasing phosphorylated these mitigated CC. Adding FA overexpressing addition, sodium-glucose cotransporter (SGLT)2 expression detected cardiomyocytes. CONCLUSION Empagliflozin partially achieves anti-oxidative anti-apoptotic under conditions activating AMPK/PGC-1α suppressing RhoA/ROCK pathway independent SGLT2.

Язык: Английский

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Grouping strategies for assessing and managing persistent and mobile substances

Опубликована: Фев. 1, 2024

Background: Persistent, Mobile and Toxic (PMT), or very Persistent (vPvM) substances are a wide class of chemicals that recalcitrant to degradation, easily transported, potentially harmful humans the environment. Due their persistence mobility, these often widespread in environment once emitted, particularly water resources, causing increased challenges during treatment processes. Some PMT/vPvM such as GenX perfluorobutane sulfonic acid have been identified high concern (SVHCs) under European Registration, Evaluation, Authorisation Restriction Chemicals (REACH) regulation. With hundreds thousands potential yet be assessed managed, effective efficient approaches avoid case-by-case assessment prevent regrettable substitution necessary achieve Union's zero-pollution goal for non-toxic by 2050. Main: Substance grouping has helped global regulation some highly hazardous chemicals, e.g., through Montreal Protocol Stockholm Convention. This article explores strategies assessing managing substances. It provides an overview reviews definition criteria various lists available. covers current groups, compares use substance hazard regulation, discusses advantages disadvantages The then substances, including read-across, structural similarity commonly retained moieties, well application using cheminformatics predict P, M T properties selected examples. Conclusion: Effective can accelerate management especially lack information. Advances read-across methods tools needed support chemical management, preventing broad entry into market favouring safer more sustainable alternatives.

Язык: Английский

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Grouping strategies for assessing and managing persistent and mobile substances

Опубликована: Март 28, 2024

Background: Persistent, Mobile and Toxic (PMT), or very Persistent (vPvM) substances are a wide class of chemicals that recalcitrant to degradation, easily transported, potentially harmful humans the environment. Due their persistence mobility, these often widespread in environment once emitted, particularly water resources, causing increased challenges during treatment processes. Some PMT/vPvM such as GenX perfluorobutane sulfonic acid have been identified high concern (SVHCs) under European Registration, Evaluation, Authorisation Restriction Chemicals (REACH) regulation. With hundreds thousands potential yet be assessed managed, effective efficient approaches avoid case-by-case assessment prevent regrettable substitution necessary achieve Union's zero-pollution goal for non-toxic by 2050. Main: Substance grouping has helped global regulation some highly hazardous chemicals, e.g., through Montreal Protocol Stockholm Convention. This article explores strategies identifying, assessing managing substances. The aim is facilitate early identification lesser-known new meet criteria, prompt additional testing, use substitution, integrate into existing risk management strategies. Thus, this provides an overview reviews definition criteria various lists available. It covers current groups, compares substance hazard regulation, discusses advantages disadvantages then substances, including read-across, structural similarity commonly retained moieties, well application using cheminformatics predict P, M T properties selected examples. Conclusion: Effective can accelerate especially lack information. Advances read-across methods tools needed support chemical management, preventing broad entry market favouring safer more sustainable alternatives.

Язык: Английский

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Grouping strategies for assessing and managing persistent and mobile substances

Опубликована: Апрель 22, 2024

Background: Persistent, Mobile and Toxic (PMT), or very Persistent (vPvM) substances are a wide class of chemicals that recalcitrant to degradation, easily transported, potentially harmful humans the environment. Due their persistence mobility, these often widespread in environment once emitted, particularly water resources, causing increased challenges during treatment processes. Some PMT/vPvM such as GenX perfluorobutane sulfonic acid have been identified high concern (SVHCs) under European Registration, Evaluation, Authorisation Restriction Chemicals (REACH) regulation. With hundreds thousands potential yet be assessed managed, effective efficient approaches avoid case-by-case assessment prevent regrettable substitution necessary achieve Union's zero-pollution goal for non-toxic by 2050. Main: Substance grouping has helped global regulation some highly hazardous chemicals, e.g., through Montreal Protocol Stockholm Convention. This article explores strategies identifying, assessing managing substances. The aim is facilitate early identification lesser-known new meet criteria, prompt additional testing, use substitution, integrate into existing risk management strategies. Thus, this provides an overview reviews definition criteria various lists available. It covers current groups, compares substance hazard regulation, discusses advantages disadvantages then substances, including read-across, structural similarity commonly retained moieties, well application using cheminformatics predict P, M T properties selected examples. Conclusion: Effective can accelerate especially lack information. Advances read-across methods tools needed support chemical management, preventing broad entry market favouring safer more sustainable alternatives.

Язык: Английский

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Duodenal-jejunal bypass improves hypothalamic oxidative stress and inflammation in diabetic rats via glucagon-like peptide 1-mediated Nrf2/HO-1 signaling

World Journal of Diabetes, Год журнала: 2024, Номер 15(2), С. 287 - 304

Опубликована: Фев. 4, 2024

BACKGROUND Type 2 diabetes mellitus (T2DM) is often accompanied by impaired glucose utilization in the brain, leading to oxidative stress, neuronal cell injury and infla-mmation. Previous studies have shown that duodenal jejunal bypass (DJB) surgery significantly improves brain metabolism T2DM rats, role of DJB improving stress inflammation condition rats remain unclear. AIM To investigate hypothalamic rats. METHODS A rat model was induced via a high-glucose high-fat diet, combined with low-dose streptozotocin injection. were divided into operation Sham groups. surgical intervention carried out on The differential expression proteins analyzed using quantitative proteomics analysis. Proteins related inflammation, hypothalamus flow cytometry, real-time PCR, Western blotting, immunofluorescence. RESULTS Quantitative analysis showed significant differences T2DM-DJB after surgery, compared T2DM-Sham groups Oxidative stress-related (glucagon-like peptide 1 receptor, Nrf2, HO-1) increased (P < 0.05) surgery. reduced inhibiting activation NF-κB decreasing interleukin (IL)-1β IL-6. factors (glial fibrillary acidic protein Caspase-3) upregulated neuroprotective (C-fos, Ki67, Bcl-2, BDNF), thereby reducing CONCLUSION improve reduce activating glucagon-like receptor-mediated Nrf2/HO-1 signaling pathway.

Язык: Английский

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Nootkatone Counteracts Melamine-Mediated Nephrotoxicity via Modulation of Intermediate Filament Proteins, Oxidative, Inflammatory, and Apoptotic Events

Drug Design Development and Therapy, Год журнала: 2024, Номер Volume 18, С. 2989 - 3004

Опубликована: Июль 1, 2024

Background: Nootkatone (NK), a bioactive sesquiterpene ketone, is major ingredient in grapefruit that has distinguished biological activities. Melamine (MM), food adulterant, was reported to induce toxic effects including renal disorders. Hence, this protocol devoted evaluate the renoprotective impact of NK toward MM-evoked damage. Methods: Rats were either exposed MM (700 mg/kg) or combination and two doses (5 10 mg/kg). Results: The results showed therapy notably decreased kidney functional parameters, along with KIM-1 NGAL expressions group. Furthermore, decrease MDA NO levels as well an elevation SOD, CAT, GSH, SOD NRF2 mRNA expression group demonstrated NK's ability enhance antioxidant defense Significant suppression inflammatory markers achieved by via lessening IL-1β TNF-α, besides downregulation NF-κB expressions. also downregulated vimentin, nestin, desmin Additionally, response exposure, hindered apoptosis decreasing caspase-3 restoring histopathological features. Conclusion: These outcomes suggest can be considered prospective candidate guard against exposure-mediated effects. Keywords: apoptosis, inflammation, intermediate proteins, melamine nephrotoxicity, nootkatone, oxidative stress

Язык: Английский

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Impact of melamine exposure on apoptotic proteins and oxidative stress markers in mouse hepatic tissue

Ankara Üniversitesi Veteriner Fakültesi Dergisi, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 27, 2024

Most melamine studies have focused on renal toxicity and its effects the liver are still not well known. We investigated apoptotic oxidative of using thirty BALB/c mice, divided into three groups. The control group received saline, while low-dose (LDM) was given 400 mg/kg (1/8 LD50) high-dose (HDM) 1600 (1/2 intragastrically (0.25 ml) for 5 consecutive days. Liver Bcl-2 caspase-3 expressions were analyzed at protein level by immunohistochemistry ELISA, also gene quantitative Real-Time PCR. In addition, total antioxidant (TAS), oxidant (TOS), stress index (OSI) levels in tissues measured spectrophotometrically. immunohistochemical expression higher LDM HDM groups compared to (p = 0.002). TOS OSI increased significantly (P

Язык: Английский

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A potential therapeutic role of resveratrol in mitigating hepatotoxicity induced by paracetamol and alcohol

Journal of Complementary and Integrative Medicine, Год журнала: 2024, Номер unknown

Опубликована: Дек. 26, 2024

Abstract Background Drug-induced hepatotoxicity, particularly from ethanol and acetaminophen (APAP), is a pressing global health challenge. This damage arises oxidative stress inflammation, manifesting as elevated liver enzymes structural alterations. Resveratrol silymarin, recognized for their antioxidant anti-inflammatory properties, offer potential hepatoprotective benefits. Methods study investigated the efficacy of resveratrol alone in combination, rat model ethanol- APAP-induced injury. Thirty Wistar rats were divided into five groups: control, ethanol-APAP, ethanol-APAP-resveratrol, ethanol-APAP-silymarin, ethanol-APAP-resveratrol-silymarin. Treatments administered orally 10 days. Serum ALT AST levels assessed, tissues underwent histological evaluation. Results Ethanol APAP administration significantly levels, alongside severe disruptions. Treatment with or silymarin normalized enzyme improved histology. Notably, combined resveratrol-silymarin treatment exhibited greater reductions superior restoration architecture compared to either alone, indicating synergistic effect. Conclusions effectively counteract hepatotoxicity by mitigating inflammation. Their use demonstrates benefit, evidenced enhanced biochemical improvements. These findings support therapeutic role these natural agents managing drug-induced

Язык: Английский

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