Oxidative Toxicity Research Articles

Novel Dual-Acting Hybrids Targeting Type-2 Cannabinoid Receptors and Cholinesterase Activity Show Neuroprotective Effects In Vitro and Amelioration of Cognitive Impairment In Vivo.

Alzheimer's disease (AD) is a neurodegenerative form of dementia characterized by the loss of synapses and a progressive decline in cognitive abilities. Among current treatments for AD, acetylcholinesterase (AChE) inhibitors have efficacy limited to symptom relief, with significant side effects and poor compliance. Pharmacological agents that modulate the activity of type-2 cannabinoid receptors (CB2R) of the endocannabinoid system by activating or blocking them have also been shown to be effective against neuroinflammation. Herein, we describe the design, synthesis, and pharmacological effects in vitro and in vivo of dual-acting compounds that inhibit AChE and butyrylcholinesterase (BChE) and target CB2R. Within the investigated series, compound 4g proved to be the most promising. It achieved IC50 values in the low micromolar to submicromolar range against both human cholinesterase isoforms while antagonizing CB2R with Ki of 31 nM. Interestingly, 4g showed neuroprotective effects on the SH-SY5Y cell line thanks to its ability to prevent oxidative stress-induced cell toxicity and reverse scopolamine-induced amnesia in the Y-maze forced alternation test in vivo.

Netrin1-carrying magnetic microspheres with magnetic field activate neurotrophin factors to guide neuronal outgrowth in vitro and in vivo

Nerve injuries often result in the failure of functional synapses connections, primarily due to the absence of neurotrophic factors and guidance at the injury sites. In response to this challenge, an effective approach involving magnetic microspheres carrying axonal guidance cue (Netrin1) was presented. These microspheres were prepared using Fe3O4 and PLGA via electrospray. Netrin1 was incorporated into structural particles that could be oriented in a magnetic field and released at the injury sites. In this study, oriented and longer axons were observed in the cortical neurons after 10 μg/mL magnetic microspheres (MMSs) treatment. Under an applied magnetic field of 5 mT, Netrin1-carrying magnetic microspheres (N@MMSs) demonstrated a more significant increase in cell viability, mitochondrial membrane potential, mRNA expressions of BDNF and NGF compared to MMSs. These findings were assessed using the cell counting kit-8, tetramethyl rhodamine fluorescence, and real time PCR assay, respectively. Furthermore, N@MMSs demonstrated significant protection against glutamate-induced neuronal oxidative toxicity, as evaluated by mitochondrial respiratory function and glycolysis stress using the Seahorse Extracellular Flux analyzer. Subsequently, N@MMSs and a magnetic field were applied to adult mice after sciatic nerve injury. Behavior analysiss, including the open field test, indicated that N@MMSs typically increased motor activity under the magnetic field and significantly decreased paw licking latency on the 14th day. Finally, both BDNF and NGF expressions increased compared to the injury group. In conclusion, N@MMSs show promise as alternative particles for nerve regeneration.

Chronic exposure to 2,2′-azobis-2-amidinopropane that induces intestinal damage and oxidative stress in larvae of Drosophila melanogaster

Embryonic development is exceptionally susceptible to pathogenic, chemistry and mechanical stressors as they can disrupt homeostasis, causing damage and impacted viability. Oxidative stress has the capacity to induce alterations and reshape the environment. However, the specific impacts of these oxidative stress-induced damages in the gastrointestinal tract of Drosophila melanogaster larvae have been minimally explored. This study used 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH), a free radical generator, to investigate oxidative stress effects on Drosophila embryo development. The results showed that exposing Drosophila eggs to 30 mM AAPH during 1st instar larva, 2nd instar larva and 3rd instar larva stages significantly reduced hatching rates and pupal generation. It increased the activity of antioxidant enzymes and increased oxidative damage to proteins and MDA content, indicating severe oxidative stress. Morphological changes in 3rd individuals included decreased brush borders in enterocytes and reduced lipid vacuoles in trophocytes, essential fat bodies for insect metabolism. Immunostaining revealed elevated cleaved caspase 3, an apoptosis marker. This evidence validates the impact of oxidative stress toxicity and cell apoptosis following exposure, offering insights into comprehending the chemically induced effects of oxidative stress by AAPH on animal development.

New health index derived from oxidative potential and cell toxicity of fine particulate matter to assess its potential health effect

Toxicological data and exposure levels of fine particulate matters (PM2.5) are necessary to better understand their health effects. Simultaneous measurements of PM2.5 oxidative potential (OP) and cell toxicity in urban areas (Beijing, China and Gwangju, Korea) reveal their dependence on chemical composition. Notably, acids (Polar), benzocarboxylic acids, and Pb were the chemical components that affected both OP and cell toxicity. OP varied more significantly among different locations and seasons (winter and summer) than cell toxicity. Using the measured OP, cell toxicity, and PM2.5 concentration, a health index was developed to better assess the potential health effects of PM2.5. The health index was related to the sources of PM2.5 derived from the measured chemical components. The contributions of secondary organic aerosols and dust to the proposed health index were more significant than their contributions to PM2.5 mass. The developed regression equation was used to predict the health effect of PM2.5 without further toxicity measurements. This new index could be a valuable health metric that provides information beyond just the PM2.5 concentration level.

Cardiovascular and renal oxidative stress-mediated toxicities associated with bisphenol-A exposures are mitigated by Curcuma longa in rats.

Curcuma longa Rhizome (CLR), due to its potent antioxidant phytochemical constituents, was investigated for its effects on bisphenol A (BPA)-induced cardiovascular and renal damage. Sixty rats were randomly selected, and grouped as control, BPA (100 mg/ kg), BPA and CLR 100 mg/kg, BPA and CLR 200 mg/kg, CLR 100 mg/kg, and CLR 200 mg/kg for 21 days. Oxidative stress indices, antioxidant status, blood pressure parameters, genotoxicity, and immunohistochemistry were determined. Rats exposed to the toxic effects of BPA had heightened blood pressure, lowered frequency of micronucleated polychromatic erythrocytes, and decreased activities of antioxidant enzymes compared with rats treated with CLR. Moreover, administration of CLR significantly (p<0.05) lowered malondialdehyde content and reduced the serum myeloperoxidase activity. Immunohistochemical evaluation revealed significantly (p<0.05) increased expressions of cardiac troponin and Caspase 3 in the BPA group compared with the CLR-treated groups. C. longa ameliorated cardiotoxic and nephrotoxic actions of bisphenol-A via mitigation of oxidative stress, hypertension, and genotoxicity.

Toxicity of Metal Oxides, Dyes, and Dissolved Organic Matter in Water: Implications for the Environment and Human Health.

This study delves into the critical issue of water pollution caused by the presence of metal oxides, synthetic dyes, and dissolved organic matter, shedding light on their potential ramifications for both the environment and human health. Metal oxides, ubiquitous in industrial processes and consumer products, are known to leach into water bodies, posing a significant threat to aquatic ecosystems. Additionally, synthetic dyes, extensively used in various industries, can persist in water systems and exhibit complex chemical behavior. This review provides a comprehensive examination of the toxicity associated with metal oxides, synthetic dyes, and dissolved organic matter in water systems. We delve into the sources and environmental fate of these contaminants, highlighting their prevalence in natural water bodies and wastewater effluents. The study highlights the multifaceted impacts of them on human health and aquatic ecosystems, encompassing effects on microbial communities, aquatic flora and fauna, and the overall ecological balance. The novelty of this review lies in its unique presentation, focusing on the toxicity of metal oxides, dyes, and dissolved organic matter. This approach aims to facilitate the accessibility of results for readers, providing a streamlined and clear understanding of the reported findings.

A Critical Appraisal of the Protective Activity of Polyphenolic Antioxidants against Iatrogenic Effects of Anticancer Chemotherapeutics.

Polyphenolic compounds, encompassing flavonoids (e.g., quercetin, rutin, and cyanidin) and non-flavonoids (e.g., gallic acid, resveratrol, and curcumin), show several health-related beneficial effects, which include antioxidant, anti-inflammatory, hepatoprotective, antiviral, and anticarcinogenic properties, as well as the prevention of coronary heart diseases. Polyphenols have also been investigated for their counteraction against the adverse effects of common anticancer chemotherapeutics. This review evaluates the outcomes of clinical studies (and related preclinical data) over the last ten years, with a focus on the use of polyphenols in chemotherapy as auxiliary agents acting against oxidative stress toxicity induced by antitumor drugs. While further clinical studies are needed to establish adequate doses and optimal delivery systems, the improvement in polyphenols' metabolic stability and bioavailability, through the implementation of nanotechnologies that are currently being investigated, could improve therapeutic applications of their pharmaceutical or nutraceutical preparations in tumor chemotherapy.

Cleistocalyx nervosum var. paniala berry extract and cyanidin-3-glucoside inhibit hepatotoxicity and apoptosis.

Excessive oxidative toxicity in liver cells is a significant risk factor that can cause cellular injury, leading to the development of chronic liver disease (CLD). Natural anthocyanins have been shown to prevent the harmful effects of oxidative toxicity in mammalian cells. Ripe Cleistocalyx nervosum var. paniala berry fruits are rich in anthocyanins, which have been reported to possess many health benefits. Therefore, this study examined the protective effect of ethanolic fruit extract of C. nervosum var. paniala (CNPE) against hydrogen peroxide (H2O2)-induced oxidative damage and cell death in human hepatoma HepG2 cells. Results showed that CNPE had strong antioxidant capabilities and high amounts of total phenolics and anthocyanins. HPLC analysis showed that CNPE consists of cyanidin-3-glucoside (C3G). Our investigations found that HepG2 cells pretreated with CNPE or anthocyanin C3G inhibited H2O2-induced cellular damage and apoptosis by increasing the viability of cells, the expression of antiapoptotic Bcl-2 protein, and the activities of cellular antioxidant enzymes, namely SOD, CAT, and GPx. Moreover, both CNPE and C3G significantly suppressed expression of apoptotic proteins (Bax and cytochrome c) and the activities of cleaved caspase-9 and caspase-3 caused by H2O2. Our results indicate that CNPE and C3G can suppress H2O2-induced hepatotoxicity and cell death through stimulation of endogenous antioxidant enzyme activities and inhibition of apoptosis pathway in HepG2 cells. These findings might support development of CNPE as an alternative natural product for preventing CLD.

Ivermectin ameliorates bleomycin-induced lung fibrosis in male rats by inhibiting the inflammation and oxidative stress

Background Idiopathic pulmonary fibrosis (IPF) is a pulmonary fibrotic disease characterized by a poor prognosis, which its pathogenesis involves the accumulation of abnormal fibrous tissue, inflammation, and oxidative stress. Ivermectin, a positive allosteric modulator of GABAA receptor, exerts anti-inflammatory and antioxidant properties in preclinical studies. The present study investigates the potential protective effects of ivermectin treatment in rats against bleomycin-induced IPF. Materials and Methods The present study involved 42 male Wistar rats, which were divided into five groups: control (without induction of IPF), bleomycin (IPF-induced by bleomycin 2.5 mg/kg, by intratracheal administration), and three fibrosis groups receiving ivermectin (0.5, 1, and 3 mg/kg). lung tissues were harvested for measurement of oxidative stress [via myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione (GSH)] and inflammatory markers (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], and transforming growth factor-β [TGF-β]). Histological assessments of tissue damage were performed using hematoxylin–eosin (H&E) and Masson’s trichrome staining methods. Results The induction of fibrosis via bleomycin was found to increase levels of MPO as well as TNF-α, IL-1β, and TGF-β while decrease SOD activity and GSH level. Treatment with ivermectin at a dosage of 3 mg/kg was able to reverse the effects of bleomycin-induced fibrosis on these markers. In addition, results from H&E and Masson’s trichrome staining showed that ivermectin treatment at this same dose reduced tissue damage and pulmonary fibrosis. Conclusion The data obtained from this study indicate that ivermectin may have therapeutic benefits for IPF, likely due to its ability to reduce inflammation and mitigate oxidative stress-induced toxicity.

Riboflavin alleviates fluoride-induced ferroptosis by IL-17A-independent system Xc−/GPX4 pathway and iron metabolism in testicular Leydig cells

Fluoride is widely found in groundwater, soil, animal and plant organisms. Excessive fluoride exposure can cause reproductive dysfunction by activating IL-17A signaling pathway. However, the adverse effects of fluoride on male reproductive system and the mechanisms remain elusive. In this study, the wild type and IL-17A knockout C57BL/6J mouse were treated with 24 mg/kg·bw·d sodium fluoride and/or 5 mg/kg·bw·d riboflavin-5′-phosphate sodium for 91 days. Results showed that fluoride caused dental fluorosis, increased the levels of ROS in testicular Leydig cells and GSSG in testicular tissue, and did not affect the iron and serum hepcidin levels in testicular tissue. Riboflavin alleviated above adverse changes, whereas IL-17A does not participate in the oxidative stress-mediated reproductive toxicity of fluoride. Based on this, TM3 cells were used to verify the injury of fluoride on Leydig cells. Results showed that fluoride increased mRNA levels of ferroptosis marker SLC3A2, VDAC3, TFRC, and SLC40A1 and decreased Nrf2 mRNA levels in TM3 cells. The ferroptosis inhibitor Lip-1 and DFO were used to further investigate the relationship between male reproductive toxicity and ferroptosis induced by fluoride. We found that the fluoride-induced decrease in cell viability, increase in xCT, TFRC, and FTH protein expression, and decrease in GPX4 protein expression, can all be rescued by Lip-1 and DFO. Similar results were also observed in the riboflavin treatment group. Moreover, riboflavin mitigated fluoride-induced increases in ROS levels and SLC3A2 protein levels. In all, our work revealed that riboflavin inhibited ferroptosis in testicular Leydig cells and improved the declined male reproductive function caused by fluoride. This study provides new perspectives for revealing new male reproductive toxicity mechanisms and mitigating fluoride toxicity damage.

Environmental sustainability assessment of softwood and hardwood seedlings production in forest nurseries: A case study from Pakistan.

This article describes the environmental impacts of producing a single seedling in forest nurseries of selected districts (i.e., Haripur, Abbottabad, and Mansehra) of Hazara Division of Khyber Pakhtunkhwa, Pakistan using the life cycle assessment (LCA) approach. This study was based on the cradle-to-gate approach which begins with the pre-nursery stage and progresses toward the main nursery before transplanting seedlings into the plantation site. Data or life cycle inventory (LCI) of seedling production were collected through questionnaire surveys and personal meetings with forest nurseries managers and workers regarding consumption of different inputs such as electricity, diesel, fertilizers, herbicides, and polyethylene bags, organic manure, and water consumption. The SimaPro software version 8.5 and the CML2000 v2.05 environmental model was applied to perform life cycle impact assessment (LCIA) for a single seedling production in forest nurseries in the study area. In line with the objectives of the study, primary data regarding inputs and outputs of the nurseries were collected from 35 nurseries in the study area by using a random questionnaire method. In addition, secondary data were taken from online databases such as Eco-invent v.3.2 CORRIM and peer-reviewed published literature. For this study, a functional unit of a single seedling was considered. Production weighted average data were modeled in the latest environmental modeling software i.e., SimaPro v.8.5 for ten US-EPA most wanted environmental impacts, such as global warming potential (GWP), abiotic depletion (AD), eutrophication potential (EP), acidification potential (AP), freshwater aquatic eco-toxicity (FAE), marine water eco-toxicity (MWE), terrestrial eco-toxicity (TE), ozone layer depletion (OLD), photochemical oxidation (PO), and human toxicity (HT). The results showed that the highest environmental impact posed by a single seedling was marine aquatic eco-toxicity (11.31360 kg 1,4-DB eq), followed by global warming potential (0.02945 kg CO2 eq) and (0.01227 kg 1,4-DB eq) human toxicity. The primary reason for these environmental burdens was the use of synthetic fertilizers in forest nurseries and the consumption of fossil fuels in nursery mechanization and transportation activities. The total cumulative energy demand for a single seedling was (0.800 MJ) with more than 90% contribution from fossil fuel energy resources such as petrol and diesel. It is therefore highly recommended to use renewable energy resources and organic fertilizers instead of chemical fertilizers in forest nurseries to avoid and minimize greenhouse gas emissions (GHS) and other toxic emissions in the study area.

A review of botany, phytochemistry, and pharmacology of the forest Natal mahogany (Trichilia dregeana Sond.)

Trichilia dregeana is an underutilized plant species native to tropical Africa and known for its nutritional and medicinal properties. The present review compiles existing information on botany, traditional uses, and chemical and pharmacological properties of T. dregeana. Multiple searches on existing literature on the traditional, medicinal, phytochemistry, and pharmacological properties of T. dregeana were conducted in online databases such as Scopus®, Google Scholar, SpringerLink®, SciELO, ScienceDirect®, PubMed® and Web of Science, as well as using pre-electronic literature sources obtained from the university library. Trichilia dregeana is used as a medicinal plant against human and animal diseases in seven countries, that is, 33.3% of the countries where the species is indigenous. The phytochemical evaluation of the plant revealed that it contains alcohols, alkanes, amides, esters, lignan, limonoids, sesquiterpenes, steroids, and triterpenoids. The pharmacological assessments showed that the crude extracts and phytochemical compounds isolated from the species demonstrated antibacterial, antifungal, antimycobacterial, antiviral, acetylcholinesterase, anti-inflammatory, antioxidant, insecticidal, prostaglandin-synthesis inhibitory, nitric oxide production inhibitory, wound healing, mutagenicity, and toxicity activities. Detailed studies focusing on toxicity and safety, mechanisms of action in vivo, and clinical research aimed at corroborating the traditional medical applications of T. dregeana are recommended.

Antioxidant and hepatoprotective effects of hypericum sampsonii

Hypericum sampsonii or Sampson’s St John’s Wort is a species of flowering plant in the Hypericaceae family. Our previous study revealed the diverse and bioactive chemical constituents of the plant. This study investigates the antioxidant activity and potential hepatoprotective of Hypericum sampsonii extract (BLD1 extract) in vitro and in vivo. The in vitro experiment was carried out with DPPH (1, 1-diphenyl-2-picrylhydrazyl) radical scavenging assay to assess the antioxidant properties of BLD1 extract. In the in vivo experiment, the hepatoprotective activity of BLD1 extract was evaluated on an acetaminophen-induced hepatotoxicity mouse model. The in vitro assay demonstrated that the extract exhibited antioxidant activity in a dose-dependent manner. In the in vivo experiments, BLD1 extract at both doses (3.6 g/kg b.w day and 10.8 g/kg b.w day) reflected the decrease in serum ALT, AST and MDA level. Hepatic histology was also investigated post-mortem to assess the degree of liver injury. The overall findings of this study demonstrate the potential hepatoprotective effect of Hypericum sampsonii in acetaminophen-induced oxidative stress and liver toxicity in mice. This study has established the efficacy of Hypericum sampsonii, which should warrant further clinical trials and applications.

Neuroprotective action of honey bee venom (melittin) against hypoxiainduced oxidative toxicity and cell death via inhibition of the TRPM2 channel

One bioactive element of honeybee venom is melittin (MEL). MEL induced oxidant and apoptotic activities through the increase of mitochondrial Zn2+ and Ca2+ in tumor cells, but it also induced neuroprotective activity by inhibiting the cell death, intracellular reactive oxygen species (iROS), and mitochondrial ROS (mROS) productions in neurons. By stimulating the TRPM2 channel, hypoxia (HPO) enhances the effects of oxidative stress and neuronal death; however, its inhibition prevents the alterations. I studied the neuroprotective effect of MEL on HPO-mediated oxidative neurotoxicity and cell death in SH-SY5Y neuronal cells by altering the TRPM2 signaling pathways. In the SH-SY5Y cells, five groups were induced as control, MEL (1 ug/ml for 24 hrs), HPO (CoCl2 and 200 M for 24 hrs), HPO + MEL, and HPO + TRPM2 antagonist (2-aminoethoxydiphenyl borate, 2APB) (100 M for 2 hrs). The amounts of cytosolic free Ca2+ were increased in the HPO group by the stimulation of hydrogen peroxide, although they were decreased in the cells by the treatment of 2APB and MEL. The amount of cytosolic free Ca2+ was higher in the HPO group than in the control group. The amounts of cell death (propidium iodide positive cell number), oxidants (mROS and iROS), mitochondrial membrane depolarization, and cytosolic free Zn2+ were higher in the HPO group than in the control and MEL groups, although their amounts were lower in the HPO + MEL and HPO + 2APB groups than in the HPO group only. In conclusion, MEL therapy reduced the amount of HPO-induced oxidative stress and neuronal deaths in SH-SY5Y cells by inhibiting TRPM2. The MEL could be considered as a potential protective component against oxidative neuronal damage caused by HPO.

A rapid and specific fluorescent probe based on aggregation-induced emission enhancement for mercury ion detection in living systems

Mercury is a harmful heavy metal that seriously threatens the environment and organisms. In this study, we combined the aggregation-induced emission mechanism and the advantages of peptides to design a novel tetraphenylene (TPE)-based peptide fluorescent probe, TPE-Cys-Pro-Gly-His (TPE-CPGH), in which the sulfhydryl group of Cys in the peptide chain and the imidazolium nitrogen provided by His were used to mimic the Hg2+ binding site of metalloproteins. The β-fold formed by Pro-Gly was used to promote the spatial coordination of the probe with Hg2+ and the formation of the coordination complex aggregates, these changes led to the “turn on” response to Hg2+. The detection of Hg2+ by TPE-CPGH not only showed high specificity and sensitivity (LOD=46.2 nM), but also had the advantages of fast response and applicability for detection over a wide pH range. Additionally, TPE-CPGH effectively detected Hg2+ in environmental samples, living cells and organisms due to its low cytotoxicity, high water solubility and cell membrane permeability. More interestingly, TPE-CPGH was also mitigated Hg2+ exposure-induced oxidative stress toxicity in vitro and in vivo.

Oxidative stress, antioxidant defense responses, and histopathology: Biomarkers for monitoring exposure to pyrogallol in Clarias gariepinus

Pyrogallol promotes free radicals leading to oxidative stress and toxicity. There are however a lack of studies on oxidative stress and the antioxidant system of fish following exposure to pyrogallol. This study measured oxidative stress markers, antioxidant responses, and histological changes in catfish exposed to pyrogallol. Fish were divided into one of four experimental groups: control only, or 1, 5 or 10 mg/L pyrogallol. After 15 days, glutathione-S-transferase in the serum was decreased in fish exposed to either 5 or 10 mg/L pyrogallol relative to controls while superoxide dismutase and total antioxidant capacity were decreased significantly in fish exposed to 1, 5, or 10 mg/L pyrogallol. Conversely, catalase was increased in serum of fish exposed to 1, 5, or 10 mg/L pyrogallol compared to controls. The liver of fish treated with 1, 5, or 10 mg/L pyrogallol had significantly higher levels of oxidative stress markers (malondialdehyde, lipid peroxidation, hydroperoxide content, oxidised protein content, and DNA fragmentation %) that varied with concentration. Catfish exposed to either 1, 5, or 10 mg/L pyrogallol presented with notable histological alterations in the intestine, kidney, and muscles with prominent fibrosis, as intense deposition of collagen fibre was observed by Masson's trichrome staining. Overall, endpoints related to oxidative stress and antioxidant defence enzymes in fish may be early biomarkers of pyrogallol exposure and contamination in aquatic ecosystems. Additional studies should characterize oxidative stress indicators for their utility as biomarkers of effect.

Potassium β–alanine – A promising agent for reducing carbon capture cost via electrochemically mediated amine regeneration

Electrochemically mediated amine regeneration (EMAR) for CO2 capture is a promising substitute for traditional organic amine–based CO2 capture by replacing the thermal process with electricity. To avoid problems such as oxidative degradation, toxicity, volatilization, and precipitation of organic amine absorbent, potassium β–alanine was suggested as an absorbent using EMAR process for the first time in this study. The CO2 absorption performance under different copper loading and chemical reactions were studied, and cyclic voltammetry, electrochemical impedance spectroscopy, chronocoulometry and the Taffel extrapolation method were used to study the electrochemical characterization. Compared to the benchmark monoethanolamine (MEA) system, a smaller potential difference between oxidation and reduction peak was acquired in the potassium β–alanine system, of which the energy consumption was only 44.1% of the MEA system at the current of 100 A/m2. The cathode Faraday efficiency in the potassium β–alanine system was 101.9% higher than that in the MEA system at the current density of 25 A/m2. Furthermore, the result of scanning electron microscope of the electrode surface after desorption showed that potassium β–alanine absorbent improved the inhomogeneity of the electrode surface and was in favor of uniform current distribution. Overall, potassium β–alanine can be used as a more environmentally friendly absorbent in the EMAR system and has great potential to further reduce the actual energy consumption and improve the Faraday efficiency and cycling performance.

Lycium barbarum polysaccharides attenuate oxidative stress and mitochondrial toxicity induced by mixed plasticizers in HepG2 cells through activation of Nrf2

AimsIn daily life, it is common for humans to be exposed to multiple phthalate esters (PAEs). However, there is limited research on the mechanisms and intervention of combined PAEs toxicity. This study aims to explore the cytotoxicity of combined PAEs and evaluate the potential of Lycium barbarum polysaccharides (LBP) in mitigating the aforementioned toxicity. Main methodsLBP (62.5, 125 and 250 μg/mL) were applied to intervene HepG2 cells treated with DEHP and DBP mixtures (50, 100, 200, 400 and 800 μg/mL). Western Blot and different kits were mainly performed in our study. Key findingsDEHP and DBP mixtures suppressed the expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and activated MAPK pathway by increasing ROS. Combined DEHP and DBP exposure reduced ATP content and inhibited the mitochondrial biogenesis pathway in HepG2 cells through oxidative stress, which in turn caused cytotoxicity. LBP reduced oxidative stress and cell death induced by mixed plasticizers, upregulated Nrf2 levels and mitochondrial biogenesis pathway levels and inhibited MAPK pathway activation. Notably, after treating HepG2 cells with Nrf2-specific inhibitor (ML385, 0.5 μM), we found that the activation of Nrf2 played a crucial role on LBP intervention of DEHP and DBP induced HepG2 cytotoxicity. SignificanceThis study not only enhances our understanding of the toxicological effects caused by combined PAEs exposure, but also has significant implications in devising strategies to mitigate the toxicological consequences of combined exposure to exogenous chemicals through the investigation of the role of LBP.

An integrated in vitro approach to identifying chemically induced oxidative stress and toxicity in mitochondria

Growing concerns exist about increasing chemical usage and the potential health risks. Developing an efficient strategy to evaluate or predict the toxicity of chemicals is necessary. The mitochondria are essential organelles for cell maintenance and survival but also serve as one of the main targets of toxic chemicals. Mitochondria play an important role in the pathology of respiratory disease, and many environmental chemicals may induce impairment of the respiratory system through mitochondrial damage. This study aimed to develop integrated in vitro approaches to identify chemicals that could induce adverse health effects by increasing mitochondria-mediated oxidative stress using the H441 cells, which have a club-cell-like phenotype. Twenty-six environmental toxicants (biocides, phthalates, bisphenols, and particles) were tested, and each parameter was compared with eleven reference compounds. The inhibitory concentrations (IC20 and IC50) and benchmark doses (BMD) of the tested compounds were estimated from three in vitro assays, and the toxic concentration was determined. At the lowest IC20, the effects of compounds on mitochondrial reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were compared. Principal component analysis and k-mean clustering were performed to cluster the chemicals that had comparable effects on the cells. Chemicals that induce mitochondrial damage at different concentrations were used for an in-depth high-tier assessment and classification as electron transport system (ETS) uncoupling or inhibiting agents. Additionally, using in vitro to in vivo extrapolation (IVIVE) tools, equivalent administration doses and maximum plasma concentrations of tested compounds in human were estimated. This study suggests an in vitro approach to identifying mitochondrial damage by integrating several in vitro toxicity tests and calculation modeling.

Key toxic components and sources affecting oxidative potential of atmospheric particulate matter using interpretable machine learning: Insights from fog episodes

Fog significantly affects the air quality and human health. To investigate the health effects and mechanisms of atmospheric fine particulate matter (PM2.5) during fog episodes, PM2.5 samples were collected from the coastal suburb of Qingdao during different seasons from 2021 to 2022, with the major chemical composition in PM2.5 analyzed. The oxidative potential (OP) of PM2.5 was determined using the dithiothreitol (DTT) method. A positive matrix factorization model was adopted for PM2.5. Interpretable machine learning (IML) was used to reveal and quantify the key components and sources affecting OP. PM2.5 exhibited higher oxidative toxicity during fog episodes. Water-soluble organic carbon (WSOC), NH4+, K+, and water-soluble Fe positively affected the enhancement of DTTV (volume-based DTT activity) during fog episodes. The IML analysis demonstrated that WSOC and K+ contributed significantly to DTTV, with values of 0.31 ± 0.34 and 0.27 ± 0.22 nmol min−1 m−3, respectively. Regarding the sources, coal combustion and biomass burning contributed significantly to DTTV (0.40 ± 0.38 and 0.39 ± 0.36 nmol min−1 m−3, respectively), indicating the significant influence of combustion-related sources on OP. This study provides new insights into the effects of PM2.5 compositions and sources on OP by applying IML models.