JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES

Therapeutic potential of bark extracts from on renal fibrosis in streptozotocin-induced diabetic rats
Gali S, Kundu A, Sharma S, Ahn MY, Puia Z, Kumar V, Kim IS, Kwak JH, Palit P and Kim HS
(MD) bark is commonly utilized in traditional medicine for diabetes prevention and treatment. The bark extract of MD is rich in prenyl or farnesyl flavonoids and stilbenes, which possess antioxidant properties. Although data suggest the potential therapeutic benefits of the use of MD in treating diabetic nephropathy (DN), the precise mechanisms underlying MD-initiated protective effects against DN are not well understood. This study aimed to assess the renoprotective properties of MD extract by examining renofibrosis inhibition, oxidative stress, and inflammation utilizing streptozotocin-induced DN male Sprague - Dawley rats. Diabetic rats were intraperitoneally injected with streptozotocin (STZ) to induce diabetes. After 6 days, these rats were orally administered MD extract (200 mg/kg/day) or metformin (200 mg/kg/day) for 14 days. The administration of MD extract significantly lowered blood glucose levels, restored body weight, and reduced urine levels of various biomarkers associated with kidney functions. Histopathological analysis revealed protective effects in both kidneys and pancreas. Further, MD extract significantly restored abnormalities in advanced glycation end products, oxidative stress biomarkers, and proinflammatory cytokine levels in STZ-treated rats. MD extract markedly reduced renal fibrosis biomarker levels, indicating recovery from renal injury, and reversed dysregulation of sirtuins and claudin-1 in the kidneys of rats with STZ-induced diabetes. In conclusion, data demonstrated the renoprotective role of MD extract, indicating plant extract's ability to suppress oxidative stress and regulate proinflammatory pathways during pathological changes in diabetic nephropathy.
Selected micro- and macro-element associations with oxidative status markers in common carp () blood serum and ejaculate: a correlation study
Helczman M, Tomka M, Arvay J, Tvrda E, Andreji J, Fik M, Snirc M, Jambor T, Massanyi P and Kovacik A
The aim of this study was to (1) determine complex interactions between macro- and micro-elements present in blood serum and ejaculate of common carp (), and (2) examine the association between alterations in these macro- and micro-elements with markers of oxidative stress. Blood and ejaculate from 10 male carp were collected in the summer period on the experimental pond in Kolíňany (West Slovak Lowland). Reactive oxygen species (ROS), total antioxidant capacity (TAC), protein carbonyls (PC), and malondialdehyde (MDA) levels were measured in blood serum and ejaculate using spectrophotometric methods. The amounts of elements (Ag, Al, Ba, Co, Li, Mo, Ca, K, Na, and Mg) in all samples were quantified using inductively coupled plasma optical emission spectrophotometry. Data demonstrated significant differences in elemental concentrations between blood and ejaculate, specifically significantly higher ejaculate levels were detected for Ag, Al, Ba, Co, Li, Mo, K, and Mg. Potassium was the most abundant macro-element in the ejaculate, while sodium was the most abundant in blood serum. Among the micro-elements, Al was predominant in both types of samples. It is noteworthy that oxidative status markers including ROS, TAC, and MDA were significantly higher in ejaculate indicating the presence of oxidative stress in reproductive tissue. The positive correlations between Mg and Ca in blood serum and ejaculate suggest these elements play a functional role in metabolic and physiological processes. In contrast, the positive correlations of Ba and Al with markers of oxidative stress indicated the association of these metals with induction of oxidative stress. Our findings provide insights into the association of metals with biomarkers of physiological function as well as adverse effects in .
Effects of anthranilic diamide insecticides on metamorphosis in the common toad (Hensel, 1867) at concentrations found in aquatic environments
Peña SVDF and Brodeur JC
Anthranilic diamides (AD) are a modern class of insecticides used as alternatives to pyrethroids and neonicotinoids, particularly against lepidopteran pests. Despite their widespread use and presence in surface waters, little is known regarding their effects on amphibians. The aim of this study was to examine the effects of environmentally-relevant concentrations of AD insecticides chlorantraniliprole (CHLO) and cyantraniliprole (CYAN) on metamorphosis of the toad . Tadpoles were exposed to CHLO or CYAN at concentrations ranging from 5 and 5000 µg/L from stage 27 until metamorphosis completion. Both insecticides produced a non-monotonic acceleration of the time required for individuals to progress through development and a decrease in the proportion of individuals completing metamorphosis, although a delay in metamorphosis was also observed at 5 µg/L of CHLO. Snout-vent length and body weight of metamorphosed toads were not markedly affected by either insecticide. CHLO was more toxic than CYAN, with a lowest observed effect concentration (LOEC) for CHLO on time to metamorphosis defined as 5 µg/L compared to 5000 µg/L for CYAN. The LOEC for reduced metamorphic success defined as 50 µg/L for CHLO compared to 500 µg/L for CYAN. As most effects occurred after stage 39, when metamorphosis depends upon thyroid hormones, it is conceivable that that AD insecticides act as endocrine disruptors. These findings suggest that contamination of surface waters with CHLO and CYAN may disrupt amphibian development in the wild and warrant further research to investigate the possibility of endocrine-disruption by ADs.
Aluminum and UV-C light on seed germination and initial growth of white oats
Puntel RT, Stefanello R, Jesus da Silva Garcia W and Strazzabosco Dorneles L
Aluminum (Al) may be beneficial to crops, but in excess becomes detrimental to the germination and initial development of seedlings. The main determining indicators are the type of crop and exposure duration. The aim of this study was to examine the influence of Al and of UV-C light on the germination and initial growth of white oats. Seeds were sown on germitest paper in a solution of 100, 200, 300, 400, or 500 mg/L of aluminum chloride and kept in a germination chamber at 20°C for a 12-hr photoperiod. Germination and seedling growth parameters were determined after 5 and 10 days. The seeds were also exposed to two doses of UV-C (0.85 and 3.42 kJ m) under aluminum chloride stress (200 mg/L). Data demonstrated that treatment with aluminum chloride significantly decrease in germination at 200 mg/L and total seedling length at 100 mg/L. Exposure of seeds to UV-C light under excess Al (200 mg/L) did not show a significant effect on germination and growth compared to control (non-irradiated). Results indicated that exposure to high concentration of Al in the medium adversely altered germination and initial growth of white oat seedlings. Although UV-C light alone was not detrimental to the germination process, treatment with UV-C light also failed to mitigate the toxic effects of Al.
Factors influencing metal concentrations in hair and nails during longitudinal follow-up of apprentice welders
Buitrago-Cortes J, Sarazin P, Dieme D, El Majidi N and Bouchard M
The aim of this study was to determine factors influencing observed increased metal biomarkers of exposure levels in a group of 116 Quebec apprentice welders during a longitudinal follow-up of exposure. Analysis of 14 metals was carried out in hair, fingernail, and toenail samples taken from participants over the course of their welding curriculum at 6 different times. Personal and socio-demographic characteristics, lifestyle habits, and other potential confounding factors were documented by questionnaire. Multivariate linear mixed-effect models were used to assess main predictors of metal concentrations in each biological matrix including increasing time of exposure throughout the curriculum (defined as the repeated measure "time" variable"). Significant associations between repeated measure "time" variable and metal levels in hair, fingernails, and toenails were found for chromium, iron, manganese and nickel. Significant associations with "time" were also noted for arsenic levels in hair and fingernails, and for barium, cobalt and vanadium levels in fingernails and toenails. The repeated measure "time" variable, hence increasing time of exposure throughout the curriculum, was the predominant predictor of elevated biological metal levels. Reduced spaces and simultaneous activities such as oxyfuel-cutting and welding in the same welding room were suspected to contribute to higher metal levels. Age, ethnicity, and annual household income exerted an effect on metal levels and considered as confounders in the models. Variations observed in metal levels between hair and nails of apprentice welders also emphasized the relevance and importance of performing multi-matrix and multi-element biomonitoring to assess temporal variations in biological metal concentrations during welding curriculum.
as a model organism for screening acetylcholinesterase reactivators
Macedo PE, Batista JES, Souza LR, Dafre AL, Farina M, Kuca K, Posser T, Pinto PM, Boldo JT and Franco JL
The widely used insecticide chlorpyrifos (CP) is known to inhibit acetylcholinesterase (AChE) activity attributed to result in various neurological disorders and acetylcholine-dependent organ functions including heart, skeletal muscle, lung, gastrointestinal tract, and central nervous systems. Enzyme reactivators, such as oximes, are known to restore AChE activity and mitigate adverse effects. The identification of compounds that reactivate AChE constitute agents with important therapeutic beneficial effects in cases of pesticide poisoning. However, the screening of novel drugs using traditional models may raise ethical concerns. This study aimed to investigate the potential of as a model organism for screening AChE reactivators, with a focus on organophosphate poisoning. The efficacy of several oximes, including pralidoxime, trimedoxime, obidoxime, methoxime, HI-6, K027, and K048, against CP-induced AChE activity inhibition in was determined , , and experiments. Molecular docking studies indicated a strong interaction between studied oximes and the active-site gorge of AChE. Data showed that selected oximes (100 μM) are effective in the reactivation of AChE inhibited by CP (10 μM) . Finally, investigations demonstrated that selected oximes, pralidoxime and K048 (1.5 ppm), reversed the locomotor deficits, inhibition of AChE activity as well as lowered the mortality rates induced by CP (0.75 ppm). Our findings contribute to utilization of as a robust model for determination of actions of identified new AChE inhibitory agents with more effective therapeutic properties that those currently in use in the clinical practice in treatment of AChE associated disorders.
Cytotoxicity, chemical, and nutritional profile evaluation of biomass extracts of the (duckweed) aquatic plant
Nati N, Galter IN, Souza Costa I, Fabre Garcia E, Amorim Lopes G, Seibert França H, Pompermayer Machado L, da Silva RMG and Tamie Matsumoto S
(duckweed) is the smallest and fast-growing aquatic plant species producing protein-rich biomass with high protein nutritional value, phytoremediation capacity, and nutrient removal from wastewater. Duckweed may also be used as a new potential bioreactor for biological products, such as vaccines, antibodies, and pharmaceutical proteins. Based upon the potential importanc of in phytoremediation and as a bioreactor the aim of this study was to (1) characterize the chemical and nutritional profiles of biomass utilizing an integrated multi-trophic aquaculture system (IMTA) and a pond, and (2) investigate the cytotoxic potential of different concentrations of organic extracts and fractions using the MTT bioassay. EDXRF and ICP-MS analyses indicated the presence of trace elements in lower amounts in relation to the biomass of in the lagoon, emphasizing the importance of plant inclusion management to reduce bioaccumulation of these elements. Analysis of mineral profiles, fatty acids, and amino acids indicated a satisfactory nutritional composition for the use of biomass as a bioproduct. Pigment analysis showed a high concentration of carotenoids, especially astaxanthin. After standardizing the controls, the MTT cell viability test was carried out utilizing rat hepatoma cell line (HTC), which are metabolizing cells that were treated with aqueous or ethanolic extracts and the dichloromethane, ethyl acetate, and methanol fractions at different concentrations. No apparent cytotoxic potential was observed following treatments, since there was no significant reduction in cell viability. Therefore, this study provides information regarding the biomass of derived from the IMTA system, which might support further research into the application of this species as a bioproduct.
Toxicity potential of a pyraclostrobin-based fungicide in plant and green microalgae models
de Freitas Oliveira T, Barbosa Vaz da Costa MF, Alessandra Costa Santos T, Dos Santos Wisniewski MJ and Andrade-Vieira LF
Pyraclostrobin-based fungicides play an effective role in controlling fungal diseases and are extensively used in agriculture. However, there is concern regarding the potential adverse effects attributed to exposure to these fungicides on non-target organisms and consequent influence exerted on ecosystem functioning. Thus, it is essential to conduct studies with model organisms to determine the impacts of these fungicides on different groups of living organisms. The aim of this study was to examine the ecotoxicity associated with exposure to commercial fungicides containing pyraclostrobin. The focus of the analysis involved germination and initial development of seedlings of 4 plant models (, and ), in addition to determining the population growth rate and total carbohydrate content in microalga . The fungicide pyraclostrobin adversely influenced growth and development of the tested plants, indicating a toxic effect. The fungicide exerted a significant impact on the initial development of seedlings of all model species examined with plants displaying the greatest susceptibility to pyraclostrobin. Plants of this species exhibited inhibitory effects on both aerial parts and roots when treated with a concentration of 4.75 mg/L pyraclostrobin. In addition, the green microalga was also significantly affected by the fungicide, especially at relatively high concentrations as evidenced by a reduction in total carbohydrate content. This commercial fungicide demonstrated potential phytotoxicity for the tested plant models and was also considered toxic to the selected microalgae, indicating an ecotoxic effect that might affect other organisms in aquatic environments.
Increasing coil temperature of a third-generation e-cigarette device modulates C57BL/6 mouse lung immune cell composition and cytokine milieu independently of aerosol dose
Poindexter ME, Li Y, Madl AK, Nguyen TB and Pinkerton KE
Higher coil temperature in e-cigarette devices increases the formation of aerosols and toxicants, such as carbonyls. At present, the health implications of vaping at higher temperatures, including exacerbation of pulmonary inflammation, are largely unknown when aerosol dose is considered. To isolate the pulmonary effects of coil temperature, C57BL/6 mice were exposed to e-cigarette aerosols generated at lower (190°C) or higher (250°C) temperature for 3 days, while maintaining a similar chamber aerosol concentration. Increasing coil temperature did not markedly alter aerosol mass-normalized emissions of select carbonyls formed from thermal degradation pathways including formaldehyde, acetaldehyde, propionaldehyde, and acetone under the tested environment. Total bronchoalveolar cells, primarily macrophages, were significantly decreased in mice exposed to aerosols generated with higher coil temperatures compared to lower temperature exposures. The gene expression of IFNβ, IL-1β, TNFα, and IL-10 in mouse lung tissue was significantly reduced following e-cigarette exposure under both conditions, compared to filtered air exposure. Higher temperature exposures further exacerbated downregulation of IFNβ and IL-1β. Data suggest that higher temperature vaping might modulate acute pulmonary immune responses, potentially inducing immune suppression, even when normalized for aerosol dose exposure. Coil temperature thus appears to be an important parameter that needs to be regulated to ensure harm reduction for e-cigarette users.
Protective effects of black ginseng on testicular toxicity induced by Di--butyl phthalate in rats
Park CJ, Sung CR, An J, Lee YJ, Oh IA, Kim S, Park YR and Kwack SJ
Di--butyl phthalate (DBP) is a phthalate-based material used as a plasticizer to soften polyvinyl chloride, and classified as an endocrine disruptor with antiandrogen effects. Exposure to DBP induces oxidative stress in rat testes, resulting in testicular toxicity. Black ginseng (BG) exhibits a higher antioxidant activity than white or red ginseng following repeated heat treatment and processing. This study aimed to investigate whether the antioxidant activity of BG might protect against DBP-induced testicular toxicity in juvenile Sprague-Dawley rats. A significant decrease in testicular weight was observed in most groups treated with DBP alone or in combination with BG. However, a significant testicular weight increase was detected after exposure to BG (10 ml/kg) + DBP (500 mg/kg). The epididymal weight was significantly reduced with associated histological changes including irregular arrangement, atrophy of seminiferous tubules and Sertoli cells, and Leydig cell damage following exposure to DBP alone as well as BG (2.5 ml/kg) + DBP (500 mg/kg). However, no marked changes were observed in the shape of seminiferous tubules in control and BG + DBP groups. A significant decrease in serum testosterone levels was found after exposure to DBP, but no marked alterations in the BG + DBP groups. Protein expression levels of nuclear factor erythroid-derived 2-related factor (Nrf2), NAD(P)H dehydrogenase 1 (NQO1), and, heme oxygenase-1; (HO-1) were significantly higher following DBP treatment, but lowered in the BG + DBP groups. Evidence indicates that BG exerts a protective effect against DBP-induced testicular toxicity in rats.
Force-induced tissue compression alters circulating hormone levels and biomarkers of peripheral vascular and sensorineural dysfunction in an animal model of hand-arm vibration syndrome
Krajnak K, Waugh S, Warren C, Chapman P, Xu X, Welcome D, Hammer M, Richardson D and Dong R
Workers regularly using vibrating hand tools may develop a disorder referred to as hand-arm vibration syndrome (HAVS). HAVS is characterized by cold-induced vasospasms in the hands and fingers that result in blanching of the skin, loss of sensory function, pain, and reductions in manual dexterity. Exposure to vibration induces some of these symptoms. However, the soft tissues of the hands and fingers of workers are compressed as a result of the force generated when a worker grips a tool. The compression of these soft tissues might also contribute to the development of HAVS. The goal of this study was to use an established rat tail model to determine the mechanisms by which compression of the tail tissues affects (1) the ventral tail artery (VTA) and ventral tail nerves (VTN), (2) nerves and sensory receptors in the skin, (3) dorsal root ganglia (DRG), and (4) spinal cord. Tissue compression resulted in the following changes (1) circulating pituitary and steroid hormone concentrations, (2) expression of factors that modulate vascular function in the skin and tail artery, and (3) factors associated with nerve damage, DRG, and spinal cord. Some of these observed effects differed from those previously noted with vibration exposure. Based upon these findings, the effects of applied force and vibration are different. Studies examining the combination of these factors might provide data that may potentially be used to improve risk assessment and support revision of standards.
The impacts of reduction in ambient fine particulate air pollution on natural-cause mortality in Taiwan
Tsai SS and Yang CY
Many epidemiologic studies have reported an association between high concentrations of fine particulate matter (PM) and increased mortality rates. Concurrently an association between decreased concentration of these airborne PM pollutants and a decline in mortality frequency was noted in certain investigations globally; however, only a very few of these studies were conducted in Asia. Taiwan was found to exhibit a 30% decline in ambient PM levels over the last 20 years. The aim of this ecological investigation was to examine the contribution of annual reductions in ambient PM to changes in age-standardized natural-cause mortality rates (ASRs) in 65 townships in Taiwan from 2006 to 2020 controlling for lung cancer mortality rate, physician density, and annual household income. Data demonstrated a 0.9/10 fall in adjusted ASR for every 10 ug/m reduction in mean annual PM level in Taiwan during this 14-year period, suggesting a significant association between reductions in ambient PM levels and decreases in natural-cause mortality rates.
Liposome preparation of alpha-arbutin: stability and toxicity assessment using mouse B16F10 melanoma cells
Viana AR, Poleze TC, da S Bruckmann F, Bottari NB, Peroza LR, Rosales I, Zago NS, Schetinger MRC, Krause LMF, Rhoden CRB and Mortari SR
Melanoma is the most aggressive type of skin cancer, with few therapeutic alternatives following metastasis development. In recent years, drug delivery-associated nanotechnology has shown promising targeted results with diminished adverse effects compared to conventional treatments. This study aimed to (1) examine the effects of plant-derived α-arbutin, a natural compound and (2) compare these findings with bioactively developed liposomes containing α-arbutin utilizing the B16-F10 murine melanoma cell line as a model. Liposomes were obtained through reversed-phase evaporation by applying a spray dryer to assess their stability. The following biologic assays were measured cytotoxicity/antiproliferative (MTT, Neutral Red, and dsDNA PicoGreen). In addition, the levels of melanin and purinergic enzymes were also measured. The production of reactive oxygen species (ROS) and nitric oxide (NO) was determined as a measure of oxidative state. Treatment with nano-liposome containing alpha-arbutin induced a significant 68.4% cytotoxicity, similar to the positive control, in the B16-F10 murine melanoma cell line at 72 hr. Further, arbutin and liposomes containing alpha-arbutin increased levels of ROS and nitrite formation at 72 hr at the highest concentration (100 and 300 µg/ml) of treatments. Arbutin and liposomes containing alpha-arbutin reduced melanin levels at all tested concentrations. In addition, arbutin and alpha-arbutin containing liposomes lowered nucleotides (AMP, ADP, and ATP) and nucleoside (adenosine) levels in melanoma cells. Evidence suggests that α-arbutin containing liposome can be considered as an alternative immunosuppressive agent stimulated in melanoma treatment.
Ethnic-racial disparities in poisoning cases: analysis of drugs of abuse, medicines and pesticides in Brazil
da Rosa Moraes NG, Florencio Ramires P, Silva da Cruz L, Oliveira Penteado J, Buffarini R and da Silva Júnior FMR
In Brazil, ethnic-racial inequalities exist in all fields, obstructing access to goods, services, and opportunities, including healthcare services. However, there are no apparent studies that assess, at a national level, ethnic-racial disparities in poisoning cases, emphasizing skin color as a determining factor. The study aimed to examine the relationship between race/ethnicity and general poisoning cases, by medications, pesticides, and drug of abuse in Brazilian states. Poisoning cases data were extracted for the years 2017, 2018, and 2019. Notification data for general poisoning cases and toxic agents were collected: medications, pesticides, and drugs of abuse. Data were categorized between whites and non-whites (blacks, browns, and indigenous) and without information on skin color/ethnicity. Rates of poisonings amongst ethnic-racial groups and cases of not declared skin color as well as relative risk (RR) of poisoning among non-whites were calculated. All states in the North, Northeast (states with the worst Human Development Index), Midwest, and 2 states in the Southeast exhibited higher rates of poisoning cases per 100,000 inhabitants among non-whites. The RR values for nonwhite individuals were higher in the North and Northeast regions for all types of poisonings. The type of poisoning cases that presented the highest RR for non-whites over the 3 years was drugs of abuse (2-2.44), when compared to other types of poisonings from pesticides (2-2.33) and medications (1.5-1.91). The spatial distribution of poisoning cases rates and RR of nonwhite population support public policies to reduce socioeconomic and environmental inequalities.
Phyto-cytogenotoxic potential assessment of two medicinal plants: (Vahl) Kubitzki and (A. St.-Hill) (Dilleniaceae)
Dos Santos FE, Rinaldo D and Vieira LFA
Humans have been using plants in the treatment of various diseases for millennia. Currently, even with allopathic medicines available, numerous populations globally still use plants for therapeutic purposes. Although plants constitute a safer alternative compared to synthetic agents, it is well established that medicinal plants might also exert adverse effects. Thus, the present investigation aimed to assess the phytotoxic, cytotoxic, and genotoxic potential of two plants from the Brazilian Cerrado used in popular medicine, (Vahl) Kubitzki, and (A. St.-Hil.). To this end, germination, growth, and cell cycle analyses were conducted using the plant model . Seeds and roots were treated with 0.0625 to 1 g/L for 48 hr under controlled conditions. The germination test demonstrated significant phytotoxic effects for both species at the highest concentrations tested, while none of the extracts produced significant effects in the lettuce growth test. In the microscopic analyses, the aneugenic and cytotoxic action of was evident. In the case of greater clastogenic action and induction of micronuclei, (MN) were noted suggesting that the damage initiated by exposure to these extracts was not repaired or led to apoptosis. These findings indicated that the observed plant damage was transmitted to the next generation of cells by way of MN. These differences in the action of the two species may not be attributed to qualitative variations in the composition of the extracts as both are similar, but to quantitative differences associated with synergistic and antagonistic interactions between the compounds present in these extracts.
Chemical composition, cytotoxicity, antimicrobial, antibiofilm, and anti-quorum sensing potential of essential oil against the oral pathogen
Quintana Soares Lopes L, Fortes Guerim PH, Maldonado ME, Wagner R, Hadlich Xavier AC, Gutknecht da Silva JL, Bittencourt da Rosa Leal D, de Freitas Daudt N, Christ Vianna Santos R and Kolling Marquezan P
Dental caries is a highly prevalent oral disease affecting billions of individuals globally. The disease occurs chemically as a result of breakdown of the tooth surface attributed to metabolic activity in colonizing biofilm. Biofilms, composed of exopolysaccharides and proteins, protect bacteria like , which is notable for its role in tooth decay due to its acid-producing abilities. While various antimicrobial agents may prevent biofilm formation, these drugs often produce side effects including enamel erosion and taste disturbances. This study aimed to examine utilization of the essential oil as a potential antibiofilm activity agent against . oil significantly (1) reduced bacterial biofilm, (2) exhibited a synergistic effect when combined with chlorhexidine, and (3) did not induce cell toxicity. Chemical analysis identified the essential oil with 99.99% certainty, revealing menthol and menthone as the primary components, constituting approximately 42% and 26%, respectively. Further, oil eradicated preformed biofilms and inhibited biofilm formation at sub-inhibitory concentrations. oil also interfered with bacterial quorum sensing communication and did not produce any apparent cell toxicity in immortalized human keratinocytes (HaCaT). represented an alternative substance for combating and biofilm formation and a potential combination option with chlorhexidine to minimize side effects. An performance assessment requires further studies.
Integrating ADMET, enrichment analysis, and molecular docking approach to elucidate the mechanism of for the treatment of inflammatory bowel disease-associated arthritis
Wahnou H, Hmimid F, Errami A, Nait Irahal I, Limami Y and Oudghiri M
Inflammatory Bowel Disease-Associated Arthritis (IBD-associated arthritis) poses a significant challenge, intertwining the complexities of both inflammatory bowel disease (IBD) and arthritis, significantly compromising patient quality of life. While existing medications offer relief, these drugs often initiate adverse effects, necessitating the requirement for safer therapeutic alternatives. , a traditional medicinal plant known for its anti-inflammatory properties, emerges as a potential candidate. Our computational study focused on examining 20 bioactive compounds derived from for potential treatment of IBD-associated arthritis. These compounds detected in include camphor, alpha-thujone, eucalyptol, cis-chrysanthenyl acetate, vicenin-2, 4,5-di-O-caffeoylquinic acid, chlorogenic acid, hispidulin, isoschaftoside, isovitexin, patuletin-3-glucoside, vanillic acid, rutin, schaftoside, lopinavir, nelfinavir, quercetin, artemisinin, gallic acid, and cinnamic acid. Following rigorous analysis encompassing pharmacokinetics, toxicity profiles, and therapeutic targets, compounds with favorable, beneficial characteristics were identified. In addition, comparative analysis with disease-gene associations demonstrated the interconnectedness of inflammatory pathways across diseases. Molecular docking studies provided mechanistic insights indicating this natural plant components potential to modulate critical inflammatory pathways. Overall, our findings indicate that -derived compounds may be considered as therapeutic agents for IBD-associated arthritis, warranting further experimental validation and clinical exploration.
The effect of biocide chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) mixture on C2C12 muscle cell damage attributed to mitochondrial reactive oxygen species overproduction and autophagy activation
Kim D, Shin Y, Baek YW, Kang H, Lim J and Bae ON
The mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT) is a biocide widely used as a preservative in various commercial products. This biocide has also been used as an active ingredient in humidifier disinfectants in South Korea, resulting in serious health effects among users. Recent evidence suggests that the underlying mechanism of CMIT/MIT-initiated toxicity might be associated with defects in mitochondrial functions. The aim of this study was to utilize the C2C12 skeletal muscle model to investigate the effects of CMIT/MIT on mitochondrial function and relevant molecular pathways associated with skeletal muscle dysfunction. Data demonstrated that exposure to CMIT/MIT during myogenic differentiation induced significant mitochondrial excess production of reactive oxygen species (ROS) and a decrease in intracellular ATP levels. Notably, CMIT/MIT significantly inhibited mitochondrial oxidative phosphorylation (Oxphos) and reduced mitochondrial mass at a lower concentration than the biocide amount, which diminished the viability of myotubes. CMIT/MIT induced activation of autophagy flux and decreased protein expression levels of myosin heavy chain (MHC). Taken together, CMIT/MIT exposure produced damage in C2C12 myotubes by impairing mitochondrial bioenergetics and activating autophagy. Our findings contribute to an increased understanding of the underlying mechanisms associated with CMIT/MIT-induced adverse skeletal muscle health effects.
Association between long-term exposure to fine particulate air pollution and risk of death attributed to esophageal cancer in Taiwan
Yang CY
The International Agency for Research on Cancer (IARC) classifies exposure to fine particulate matter (PM) air pollution as carcinogenic to humans (Group I), most frequently associated with lung cancer. Airborne air pollutants may be associated with other sites of cancer, although few studies have examined this avenue of research. Esophageal cancer mortality rates vary substantially across townships in Taiwan, a fact that suggests environment influence. Therefore, the aim of this study was to investigate the association between long-term exposure to ambient PM and deaths attributed to esophageal cancer in 66 municipal areas across Taiwan. To conduct this study, annual PM levels were determined taking into account age-standardized esophageal cancer mortality rates in male and female residents of these municipalities from 2012 to 2021. The annual PM levels of each municipality were divided into tertiles and computed adjusted risk ratio (RR) using weighted-multiple regression analyses controlling for municipal lung cancer deaths, urbanization level, and physician density. Men residing in those areas with intermediate PM tertile levels (18.96-25.19 ug/m) were found to have an adjusted RR of 1.22 (1.15-1.30) and those of residing areas with the highest tertiles levels (25.20-29.48 ug/m) exhibited an RR of 1.11 (1.051.18). However, in women in the same municipalities, a significant inverse association was found between PM levels and mortality attributed to esophageal cancer, 0.82 (95% CI = 0.65-1.04) and 0.61 (95% CI = 0.47-0.79), respectively. These findings suggest that long-term exposure to PM increases the risk of developing esophageal cancer in men in Taiwan.
Using the National Land Cover Database as an indicator of shrub-steppe habitat: comparing two large United States federal lands with surrounding regions
Burger J, Gochfeld M, Brown KG, Cortes M, Ng K and Kosson D
There is a need to assess whether ecological resources are being protected on large, federal lands. The aim of this study was to present a methodology which consistently and transparently determines whether two large Department of Energy (U.S. DOE) facilities have protected valuable ecological lands on their sites compared to the surrounding region. The National Land Cover Database (2019) was used to examine the % shrub-scrub (shrub-steppe) and other habitats on the DOE's Hanford Site (HS, Washington) and on the Idaho National Laboratory (INL), compared to a 10-km and 30-km diameter band of land surrounding each site. On both sites, over 95% is in shrub-scrub or grassland, compared to the surrounding region. Approximately 70% of 10 km and 30-km bands around INL, and less than 50% of land surrounding HS is located in these two habitat types. INL has preserved a significantly higher % shrub/scrub habitat than HS, but INL allows grazing on 60% of its land. HS has preserved a significantly higher % grassland than INL but no grazing on site is present. The methodology presented may be used to compare key ecological habitat types such as grasslands, forest, and desert among sites in different parts of the country. This methodology enables managers, resource trustees, and the public to (1) make remediation decisions that protect resources, (2) assess whether landowners and managers have adequately characterized and protected environmental resources on their sites, and (3) whether landowners and managers have protected the integrity of that land as well as its climax vegetation.
Mass spectrometry (MS)-based metabolomics of plasma and urine in dry eye disease (DED)-induced rat model
Kim HY, Lee JD, Kim H, Kim Y, Park JJ, Oh SB, Goo H, Cho KJ and Kim KB
Dry eye disease (DED) is an ophthalmic disease associated with poor quality and quantity of tears, and the number of patients is steadily increasing. The aim of this study was to determine plasma and urine metabolites obtained from DED scopolamine animal model where dry eye conditions (DRY) are induced. It was also of interest to examine whether DED (scopolamine) rat model was exacerbated by treatment with benzalkonium chloride (BAC). Subsequently, plasma and urine metabolites were analyzed using liquid chromatography (LC) and gas chromatography (GC)-mass spectrometry (MS), respectively. Data demonstrated that DED indicators such as tear volume, tear breakup time (TBUT), and corneal damage in the DED groups (DRY and BAC group) differed from those of control (CON). Similar results were noted in inflammatory factors such as interleukin (IL-1β), IL-6, and tumor necrosis factor (TNF)-α. In the partial least squares-discriminant analysis (PLS-DA) score plots, the three groups were distinctly separated from each other. In addition, the related metabolites were also associated with these distinct separations as evidenced by 9 and 14 in plasma and urine, respectively. Almost all of the selected metabolites were decreased in the DRY group compared to CON, and the BAC group was lower than the DRY. In plasma and urine, lysophosphatidylcholine/lysophosphatidylethanolamine, organic acids, amino acids, and sugars varied between three groups, and these metabolites were related to inflammation and oxidative stress. Data suggest that treatment with scopolamine with/without BAC-induced DED and affected the level of systemic metabolites involved in inflammation and oxidative stress.