Toxicology Reports最新文献

Thermal spray, in general, is a process that involves forcing a melted substance, such as metal or ceramic in the form of wire or powder, onto the surface of a targeted object to enhance its desired surface properties. In this paper, the melted substance is metal wire generated by an electric arc and forcibly coated on a rotary iron substrate using compressed air. This thermal process is referred to as double-wire arc thermal spray. The particles generated through these methods fall within the nanometer to micrometer agglomerate size range. There is concern regarding potential human health outcomes as these particles exhibit a similarity in particle morphology to welding fumes. Thermal spray wires with zinc (PMET540), iron and chromium (PMET731), and nickel (PMET885) as primary metal compositions were used to generate particulate via an electric arc wire thermal spray generator for exposure to human bronchial cells (BEAS-2B) to examine comparative toxicity ranging from 0 to 200 µg/mL. Resulting cellular viability was assessed through live cell counts, and percent cytotoxicity was measured as a function of LDH release. Oxidative stress, genotoxicity, and alteration in total antioxidant capacity were evaluated through DNA damage (COMET analysis) and antioxidant concentration at 0, 3.125, 25, and 100 µg/mL. Protein markers for endothelin-1 (ET-1), interleukin-6 (IL-6), and interleukin-8 (IL-8) were also assessed to determine inflammation and endothelial alteration.

Results: indicate modulation of oxidative stress response in a material and dose dependent manner. PMET540 exhibited the greatest cytotoxic effect between wires and across doses. DNA damage and antioxidant concentration induced by PMET540 were significantly higher than other wires at higher doses (DNA damage increased at 25 and 100 µg/mL; Antioxidant concentration increased at 100 µg/mL). However, ET-1 concentration significantly increased only after application of 100 µg/mL PMET885. IL-6 and IL-8 were most highly expressed in BEAS2B culture after 25 µg/mL exposure to PMET540 (99.4 % Zn). This data suggests that metal composition of thermal spray wires dictates the diverse response in human bronchial cells.

Occupational exposures are generally complex, workers are exposed with more than one hazardous agent in work environment. Combined exposure to noise and benzene is common in occupational environments. Sub-acute exposure to benzene vapors can induce oxidative stress in serum. Additionally, noise exposure leads to non-auditory effects, such as oxidative stress. However, In the authors' research scope, a study aimed at investigating the effect of co-exposure to noise and benzene on the oxidative stress of rat serum has not been found. The purpose of this study is to investigate the effect of co-exposure to noise and benzene on oxidative stress. In this study, 24 Wistar albino male rats were divided into four groups: the control group (1), the group exposed to white noise with an intensity of 100 dB and a frequency of 250-8KHz (2), the group exposed to benzene vapors with a concentration of 300 PPM (3), and the group co-exposed to white noise with an intensity of 100 dB and benzene vapors with a concentration of 300 PPM. Oxidative stress induced was investigated by serum oxidative stress indices, including lipid peroxidation (MDA), total oxidative capacity (TOS), and antioxidant activity indices (SOD) and (GSH), as well as total antioxidant capacity (TAC).The results showed that exposure to noise and benzene, both separately and combined, can lead to oxidative stress in rat serum, increasing serum oxidant indices MDA and TOS while decreasing serum antioxidant indices TAC, SOD, and GSH was detected in groups exposed to noise and benzene. The findings indicate that the serum oxidative stress caused by the co- exposure to noise and benzene is significantly higher than separate exposure to noise or benzene, also Co-exposure to noise and benzene can have an almost additive effect on increasing serum oxidative stress in rats. This study highlights the importance of studying co-exposure to physical and chemical hazardous agents in the work environment.

Pesticides are widely used to control pests, but their widespread use raises concerns regarding potential health risks for humans. There are several routes through which pesticides can be ingested, inhaled, and absorbed, resulting in acute and long-term health consequences. This systematic review synthesizes the available evidence regarding the health risks and long-term effects of pesticide exposure, with a particular focus on epidemiological and toxicological studies. A systematic review was conducted by searching scientific databases i.e. Scopus, and Web of Science for peer-reviewed articles published between 2000 and 2024. Studies were selected based on their focus on pesticide exposure, health risks, and long-term effects. Meta-analysis was conducted where sufficient homogeneity of outcomes allowed. This review identified consistent associations between chronic pesticide exposure and non-communicable diseases, including cancer, neurological disorders, and endocrine disruptions. An increased incidence of respiratory issues and neurodegenerative diseases was often associated with occupational exposure to pesticides. People exposed for a prolonged or high intensity time period, particularly agricultural workers, were more likely to experience long-term health effects. There are a number of factors that influences the ability to draw definitive conclusions, including variations in pesticide types, exposure levels, and health outcomes. Chronic exposure to pesticides presents significant health risks, particularly for individuals in high-exposure environments like agriculture. While evidence indicates strong associations with several long-term health conditions, additional research is necessary to elucidate dose-response relationships and mechanisms of action. This review underscores the necessity for enhanced regulatory measures and improved safety protocols to mitigate pesticide-related health risks.

Background: Salvia blancoana subsp. mesatlantica (Maire) Figuerola (SBm) is a plant endemic to Morocco and is one of the less studied species of Salvia. Herbal therapy is becoming more and more popular, especially in underdeveloped nations where access to medicinal herbs is affordable. However, some plants demonstrated toxic effects in animals and humans.

Objective: Our study aimed to evaluate the SBm-extract for both acute and sub-chronic toxicity.

Methods: Aqueous extracts were obtained from the aerial parts of SBm collected from Immouzer Kander commune (Middle Atlas, Morocco). Total Phenolic Content (TPC) and Flavones and flavonols Content (FFC), Antioxidant activity (2,2-diphenyl-1-picrylhydrazyl (DPPH) and reducing power) was determined, and chemical composition was determined by High-Performance Liquid Chromatography with Diode Array Detection (HPLC-DAD). Toxicity tests were conducted on mice and rats.

Results: In acute toxicity, Swiss albino mice (mass of 25-35 g) received SBm-extract orally and intraperitoneally at doses (0.5-11 g/kg, bm). The sub-chronic toxicity was tested in Wistar albino rats (mass of 200-240 g) for 90 days at doses of 0, 250, 500, or 1000 mg/kg, bm. Values of TPC and FFC were estimated to be 157.56 ± 0.32 mg GAE/g DW and 7.89 ± 0.05 mg QE/g DW, respectively. DPPH scavenging (IC₅₀) was estimated to be 26.9 ± 0.08 µg/mL while reducing power was 12.41 ± 0.03 µg/mL. No toxicity or deaths were observed in acute tests after oral exposure, while intraperitoneal administration resulted in dose-dependent acute toxicity, with an LD₅₀ value of 6.82 g/kg. In sub-chronic tests, most hematological and biochemical parameters remained unchanged, except for transient fluctuations in specific blood constituents and a transitory reduction in serum glucose levels observed at elevated dosages. Histopathological investigation revealed no organ abnormalities. The SBm-extract exhibited minimal toxicity, supporting its safe use.

Conclusions: Despite the relevant results of this study, future studies need to confirm these findings and expand our understanding of the safety characteristics of Salvia. Further investigations are needed to explore the effects of other solvents on the extraction of bioactive compounds from the underground and aerial parts of this endemic species. Evaluation of other biological properties such as anti-microbial, anti-cancer, and anti-inflammatory activities are needed.

Doxorubicin (DOX) is a cytotoxic anthracycline used to treat a variety of cancers. Cardiotoxicity, hepatotoxicity, and nephrotoxicity are adverse effects of DOX, that limit prognosis. The study aims to determine if diosmin (DIOS) and coenzyme Q10 (CoQ10) alone or in combination protect rats against DOX-induced liver and kidney damage. Adult male rats were assigned randomly in five groups. An intraperitoneal injection of DOX (2.5 mg/kg) was given to the DOX group every other day for three weeks, whereas a normal control group received the vehicle. Diosmin group received oral DIOS (100 mg/kg), Co-Q10 group received oral CoQ10 (10 mg/kg) and combination group received oral DIOS and CoQ10 daily for three weeks concomitantly with DOX. Sera and tissues were obtained 24 hours after last DOX injection. Serum aspartate transaminase (AST), alanine transaminase (ALT), creatinine, urea, total bilirubin and direct bilirubin were detected with hepatic and renal reduced glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and nuclear factor kappa-B (NF-κB). Histopathology and morphometry of liver and kidney were assessed. DOX exerted significant hepatorenal toxicity via elevation of liver and kidney functions, inducing oxidative stress by reducing GSH and elevating MDA, triggering renal and hepatic TNF-α and NF-kB. DIOS and CoQ10 modulated hepatic and renal functions, oxidative stress and inflammatory biomarkers. DIOS-CoQ10 combination treatment showed significant improvement in histopathology of liver and kidney along with morphometry compared to DOX group. In conclusion, combining DIOS and CoQ10 exhibited synergistic protective activity against DOX-induced hepatic and renal insult via their antioxidant and anti-inflammatory properties.

The use of pesticides in commercial farms can lead to exposure among various vulnerable groups. This study assessed the distribution, human health risks, and origins of 13 targeted organochlorine pesticides (OCPs) in soil samples from commercial farms in Southern Nigeria. Following a questionnaire survey on pesticide usage, soil samples were subjected to Soxhlet extraction and analyzed using gas chromatography-mass spectrometry. Results indicated that 31.6 % of farmers did not use personal protective equipment, and only 37.6 % had received training on safe pesticide application. While pyrethroids and organophosphates were commonly used, organochlorines were rarely applied. The detected levels of OCPs in the agricultural zones ranged from below detection limit (BDL) to 18.35 ± 13.83 µg/kg and were generally within the minimum risk level (MRL), except for α-HCH and β-HCH in Oron and Etinan zones. The estimated non-carcinogenic risk s from detected OCPs were insignificant at the time of the study, as the calculated Hazard Indexes (HIs) and Hazard Quotients (HQs) for ingestion, dermal absorption, and inhalation were all less than 1, indicating generally low risks. The carcinogenic risk assessment showed that the Incremental Lifetime Cancer Risk (ILCR) values ranged from 10^-10 to 10^-4, indicating a very low to low risk level according to the classification by the United States Agency for Toxic Substances and Disease Registry (US ATSDR). Source apportionment suggested that most OCP congeners were of historical origin, with only a few indicating recent use. In conclusion, organochlorine pesticide residues in the studied farms posed minimal health risks, with most originating from historical rather than recent use.

Squamous carcinoma of the head and neck is characterized by aberrant apoptosis that prolongs the proliferative capacity of the cells and by uncontrolled cell growth. This study aimed to examine the pro-apoptotic and antiproliferative effects of Caesalpinia pulcherrima cassane diterpenoids on squamous carcinoma cells in vitro. The cytotoxicity of four (4) cassane diterpenoids {Six-cinnamoyl- 7-hydroxyvouacapen-5-ol(1), pulcherrimin A(2), C(3), and E(4)} isolated from C. pulcherrima was determined in squamous carcinoma cell lines (CAL33, FaDu, and Detroit 562) and in non tumorigenic fibroblast cells. The results showed that compounds 1 and 4 had the highest cytotoxic potential, significantly reducing cell viability in all squamous cell lines in a concentration dependent manner. Compounds 1 and 4 may inhibit the proliferation of CAL33 cells by reducing their ability to divide, decreasing PCNA expression, and suppressing migration. Additionally, treatment with compounds 1 and 4 led to an activation of Caspase 3 expression in FaDu cells. Molecular docking analysis revealed strong binding affinities of compounds 1 and 4 to the Caspase 3 receptor, with values of -8.5 and -8.8 kcal/mol, respectively. These results suggest that Pulcherrimin E and 6-cinnamoyl-7-hydroxylvouacapen-5-ol have potential antitumor effects based on their selective cytotoxic effect on squamous carcinoma cells in vitro.

Background: Plastic products use phthalate to enhance their flexibility, transparency, and stability, while behenic acid is a carboxylic acid with antioxidant activity.

Objectives: This study evaluates whether behenic acid can protect the testosterone cycle and prevent the sperm apoptosis and protein loss in phthalate-treated male rats.

Methods: There were 36 male albino rats in all, divided into six equal sets of six rats each: control, behenic acid (13 g/kg), behenic acid (26 g/kg), diethyl phthalate (10 mg/kg), behenic acid (13 g/kg) + diethyl phthalate (10 mg/kg), and behenic acid (26 g/kg) + diethyl phthalate (10 mg/kg)-treated groups. Measurements were made of serum male hormones, sex hormone-binding globulin, sodium/potassium ATPase, superoxide dismutase, glutathione, glucose-6-phosphate dehydrogenase, 3β-hydroxysteroid dehydrogenase, protein, and cholesterol in the testis, as well as malondialdehyde in the sperm, testis, and hypothalamus. Sperm monoclonal proliferating antibody Ki-67, sperm counts, motility, and abnormalities were measured.

Results: Oral administration of diethyl phthalate increased malondialdehyde, serum follicle stimulating hormone, sex hormone binding globulin, luteinizing hormone, glucose-6-phosphate dehydrogenase, 3β-hydroxysteroid dehydrogenase, cholesterol, total protein, sperm abnormality, and the percentage of spermatogonia, first spermatocyte, second spermatocyte, and spermatid in the testis. Superoxide dismutase, glutathione, serum testosterone and dehydroepiandrosterone sulphate, sperm count and motility, and sodium/potassium-ATPase activity were all reduced. Additionally, all of the previously described parameters reverted to near control values after receiving two doses of behenic acid in phthalate-treated rats; a higher dose of behenic acid had a more effective effect than a lower dose.

Conclusion: behenic acid can protect the testosterone cycle and prevent the sperm apoptosis and protein loss in phthalate-treated male rats by inhibiting oxidative stress and stimulating ATPase activity.

In view of inconsistent reports on the association between chronic lead (Pb) exposure and renal injury markers (potential site of injury), the present systematic review explored their association by reviewing studies that investigated chronic Pb-exposed and those without obvious Pb exposure. Studies reporting blood Pb levels(BLL) and biomarkers of kidney injury [i.e. N-acetyl-β-D-glucosaminidase (NAG), Micro-Globulin(μG) and others] among chronic Pb-exposed and unexposed individuals were systematically searched from digital databases available until February 26, 2024. Preferred Reporting Items of Systematic Reviews and Meta-Analysis Guidelines were adhered to during the execution. Pooled effect size and heterogeneity were estimated using the random effect model and I2Studies reporting blood Pb levels(BLL) and biomarkers of kidney injury [i.e. N-acetyl-β-D-glucosaminidase (NAG), Micro-Globulin(μG) and others] among chronic Pb-exposed and unexposed individuals were systematically searched from digital databases available until February 26, 2024. Preferred Reporting Items of Systematic Reviews and Meta-Analysis Guidelines were adhered to during the execution. Pooled effect size and heterogeneity were estimated using the random effect model and I2. Pooled quantitative analysis revealed elevated BLL [25.64 (21.59-29.70) µg/dL] Pb-exposed group. The pooled analysis confirmed significantly higher urinary NAG [0.68(0.26-1.10) units], α1μG [3.82(0.96-6.68) mg/g creatinine] β₂μG [1.5(0.86-2.14) units and serum creatinine [0.03(0.00-0.05) mg/dL] levels in Pb-exposed group, with high heterogeneity. Current observations indicate the proximal tubular injury as the early and potential site of Pb-induced renal injury. Pb-exposed individuals experience proximal tubular injury (KIM-1, NAG) and dysfunction (β2μG, α1μG, Cystatin-C) prior to obvious clinical renal failure. Present observations should caution the policymakers towards drafting regulations for periodic screening with markers of renal injury and / or dysfunction among those chronically exposed to lead despite the certainty of evidence is very low.

Background: Due to their variability and safety, widespread research on phytochemicals continually encourages researchers to study various plants for their potential health benefits.

Objectives: This study aims to explore the phytochemical constituents of the aerial parts of three Mesembryanthemum spp.; M. nodiflorum, M. forsskaolii, and M. cordifolium existed in Egyptian nature using GC-MS analysis and studying their different biological activities in correlation to computational analysis.

Methods: Investigation of in vitro anti-inflammatory and anticancer activities and in silico studies of identified major compounds on VEGFR. Results: Thirty-three compounds were identified, octadecanoic acid, 2, 3-dihydroxypropyl ester, and 1H-Indene, 1-hexadecyl-2, 3-dihydro are the common compounds in the three extracts with different percentages. M. forsskaolii is the most extract with diverse phytoconstituents showing significant anticancer properties against the CACO2 cells with IC₅₀ value equal to 31.78 µg/mL. Nevertheless, all extracts showed potent anti-inflammatory activity at high concentrations (500 µg/mL). M. nodiflorum, M. forsskaolii, and M. cordifolium had IC₅₀ on HepG2 cells equal to 73.64, 88.18, and 87.82 µg/mL. Molecular findings showed the three extracts had distinct effects on apoptosis modulation in HepG2 cells. Conclusion The findings suggest that the studied extracts had potential therapeutic properties as anti-inflammatory and anticancer agents, supported by an in-silico interaction study.