Toxicology Reports最新文献

With an obsolete livestock sector, Gabon relies on its huge hydrographic network rich in fish to supply its populations with animal proteins. This study aimed to conduct metal analyses in four fish species (Oreochromis niloticus, Clarias gariepinus, Chrysichthys nigrodigitatus, Polydactylus quadrifilis) frequently consumed by human populations in the Moyen-Ogooué and Haut-Ogooué Provinces of Gabon and infer the potential human health risks for those populations who rely on these freshwater produces as a source of proteins. Fish were sampled from Ezanga, Oguemoué, Onangué, Nguenè (Moyen-Ogooué) and Grand Poubara (Haut-Ogooué) Lakes during the high flow period (HF) and low flow period (LF) from 2021 to 2022, and analysed for seven heavy metals (HMs) using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) techniques. Throughout the flow periods, and regardless of the lake and fish species, Fe was found to have the highest concentration, followed by Al > Mn > Hg > Pb> As> Cd. The relatively high concentration of Hg was recorded in the muscle tissues of C. gariepinus (6.65 mg. kg^-1) sampled during the LF period at Grand Poubara. The concentrations of Hg found in the muscle of all fish species also exceeded the maximum acceptable limits set by the American Environmental Protection Agency. The concentrations of Fe in C. gariepinus (Grand Poubara, LF) and O. niloticus (Onangué, LF), and those of Al in O. niloticus (Nguenè, HF), P. quadrifilis (Onangué, HF) and C. nigrodigitatus (Oguemoué, LF) were amongst the highest concentrations ever reported on the African continent. Health risk assessments indicated a heightened risk of cancer for local populations consuming the fish species from all the lakes investigated. There is a need to implement an increased surveillance programme at national level in order to raise awareness and improve the management of fishery resources while preserving the environment and the health of local populations that rely upon these resources for their subsistence.

Warfarin, a commonly prescribed anticoagulant, is utilized to prevent thrombotic issues and requires careful dose adjustment due to its narrow therapeutic range. As warfarin is metabolized by essential drug-metabolizing enzymes (DMEs), it is prone to interactions with a wide range of therapeutic agents, including herbal medicines. In June 2022, Thailand became the first country in Asia to remove cannabis plants from its narcotics control list, allowing individuals to cultivate them for personal use. Consequently, this report aimed to examine the interaction between cannabis and warfarin in Thai patients following the legalization of cannabis from 2021 to 2023. These three case reports elucidated the potential for drug interactions arising from the concurrent use of warfarin and water-boiled cannabis. This process involved placing cannabis flowers into a boiling kettle and subsequently consuming the resulting cannabis-infused water instead of regular drinking water. Our findings revealed that each atrial fibrillation patient had supratherapeutic international normalized ratio (INR) levels ranging from 3.49 to 4.92, with no bleeding complications. Following the cessation of cannabis use, the INR levels decreased and returned to the therapeutic range for warfarin therapy. In summary, the current report indicates that water-boiled cannabis may influence the outcomes of warfarin therapy, as evidenced by the changes in INR levels.

The effect of EMS at final concentration of 0.09, 0.18, 0.27 and 0.37 mM was studied on Hydra vulgaris using morphological, regeneration, oxidative stress markers and DNA damage as parameters. The morphological scores showed a significant dose dependent difference in the Hydra exposed to 0.18, 0.27, and 0.37 mM of EMS for 24, 48, 72 and 96 h. The regeneration scores also showed a significant difference in the gastric region of Hydra exposed to 0.37 mM of EMS for 48 h. A significant difference in the scores of regeneration was observed for the mid body portion exposed to 0.18, 0.27 and 0.37 mM of EMS for 72 and 96 h of duration compared to control. A dose-dependent significant increase in the activities of glutathione-S-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) was observed compared to control. The thiobarbituric acid reactive species (TBARS) levels were also significantly increased compared to control. The genotoxic damage was assessed in the cells of gastric region of the Hydra exposed to 0.09, 0.18, 0.27 and 0.37 mM of EMS for 48 h by performing comet assay. A significant dose-dependent increase in the DNA damage was observed compared to control.

Antibiotics are indispensable in modern healthcare, playing a critical role in mitigating bacterial infections. Azithromycin is used to fight upper respiratory tract infections, however has potential toxic effects that remain inadequately understood. In our present study, azithromycin exposure to Caenorhabditis elegans led to significant physiological and behavioral change, with pronounced effects observed at the studied concentration. The study employs an N2 wild-type strain to examine key physiological and behavioral parameters within the worm. C.elegans were exposed to two concentrations of azithromycin (0.0038 and 0.00038 mg/ml) from the embryonic stage to the L4 stage for 48 hours. The study assessed key endpoints including body length, thrashing behavior, brood size, embryonic viability, lipid accumulation via Nile red staining, pharyngeal pumping rate, and response to 1-Nonanol (which assesses neurotransmitter function). Results showed that at 0.0038 mg/ml, azithromycin significantly reduced body length, increased progeny production, altered lipid deposition, delayed response to 1-Nonanol, and decreased feeding rates. Even at the lowest concentration (0.00038 mg/ml), changes in body length and lipid accumulation were observed. These findings suggest that the toxicity of azithromycin in C.elegans is dose-dependent and varies with exposure duration and developmental stage. Further research is needed to elucidate the molecular mechanisms underlying these toxic effects, particularly at environmentally relevant concentrations of azithromycin.

Aquatic ecosystems, critical for biodiversity and food production, confront escalating threats from anthropogenic activities like pollution and climate change, impacting fish health. This review outlines various assays used to study organ damage in fish, ranging from traditional histopathology to advanced molecular and biochemical methods. The aim is to guide researchers in selecting suitable assays for their specific questions, considering the advantages and limitations of each technique. Covered methods include histopathological assessment, biomarker analysis, genotoxicity assays, oxidative stress indicators, and non-invasive imaging. The review explores their application in monitoring environmental stressors' impacts on fish organs, emphasizing emerging trends like omics technologies and non-destructive imaging for comprehensive assessments. These innovations hold promise for early detection and understanding the implications on fish populations and ecosystem health.

This study aimed to evaluate the clot-lysing and membrane stabilizing capacities of ascorbic acid (AA) using in vitro and in silico methods. For this, we used in vitro clot lysis and hemolyzing tests to check the anti-atherothrombosis and membrane-stabilizing properties of AA, respectively. Additionally, molecular docking studies were performed to investigate AA's interactions with cyclooxygenase-1 (COX-1) and plasminogen enzymes. Findings suggest that AA exhibited a concentration-dependent effect, with 43.95 ± 1.27 % clot lysis and 64.46 ± 0.01 % membrane stabilization at 100 µg/mL. The IC₅₀ values for clot lysis and membrane stabilization were 215.19 ± 1.09 and 57.21 ± 2.11 µg/mL, respectively. In silico analysis showed strong binding affinities of AA with COX-1 (-6.2 kcal/mol) and plasminogen (-5.8 kcal/mol), supporting its observed clot lysis and membrane protection activities. Taken together, AA showed moderate clot-lysing and robust membrane-stabilizing effects, which may be due to its strong antioxidant and anti-inflammatory properties. AA might be a good therapeutic agent for atherothrombosis and membrane damage, highlighting the need for further investigation into its underlying molecular mechanisms and potential clinical applications. AA shows promising clot-lysing and membrane-stabilizing effects, highlighting its therapeutic potential for atherothrombosis and membrane damage.

Aflatoxins in food and feed with prominent toxic effects have jeopardized public health for decades. This investigation intends to explore synthesized SDS-modified chitosan as new generation of binder for removal of aflatoxin using a straightforward ionic cross-linking approach. The primary objective of this technique was to enhance affinity and adsorption capability of SDSCS towards aflatoxins. In this context, physicochemical properties of SDSCS characterized with advanced analytical techniques such as scanning electron microscope (SEM) coupled with energy dispersive X-ray spectroscopy (EDS) and Fourier transform infrared spectroscopy (FT-IR) before and after removal of aflatoxin. In this study, effect of the pH on the adsorption of aflatoxins (6ppb) indicated that the increase in SDSCS concentration from low (0.5) to high (2 %) resulted in an increase of about 80 %, 78 % and 81 % in the adsorption percentage of AFB₁, AFG₁, and AFB₂ & AFG₂, respectively. FT-IR analysis showed the intramolecular interactions of the amine groups of chitosan and sulfate group of SDS formed a stable complex in the removal of aflatoxin that verified with appearance of three new additional peaks at 1323.50, 984.34 and 603.42 cm^-1. Notably, SEM images revealed that the porous SDSCS network was filled with aflatoxin molecules supported with EDS findings. Also, in vitro cytotoxicity assessments demonstrated that SDSCS protected HepG₂ cells against cytotoxic effect caused by aflatoxin (5 µM) in a concentration-dependent manner compared to the control (p<0.01). Collectively, the adsorption mechanism may involve attraction of anionic aflatoxin molecule into the interconnected pores of SDSCS complex with numerous cationic active site via hydrogen bond and van der waals force.

Fibroblasts are native residents in dermal layer of human skin which are important for dermal regeneration and essential during cutaneous wound healing by releasing inflammatory markers and actively migrate to close an open wound. Premature skin ageing due to methylglyoxal (MGO) has recently caught the attention considering its potential to accelerate the emergence of skin ageing signs, however previous studies were only focused in primary neonatal dermal fibroblast and NIH3t3 fibroblast cell line. Therefore, thorough investigation is required to study the impact of MGO on primary human dermal fibroblast isolated from adult subject (HDFa). In our experiments, short exposure of MGO was observed to induced significant reductions in cell viability at concentrations of 7.5, 10, 12.5, 15, and 17.5 mM (p < 0.005) after 3 hours of treatment. The cellular death of HDFa at 10, 12.5 and 15 mM of MGO were also marked by increased in intracellular ROS level, indicating the involvement of oxidative stress-induced death in these cells. We also observed enlarge scratch areas of cells exposed with 7.5 and 10 mM MGO compared to control after 26 hours, thereby suggesting a decline in cell migration and viability in this group. We propose the increased ROS as the consequence of AGE-RAGE activation which was marked by significant elevation of RAGE mRNA on cells exposed to 10 mM MGO. Our data also suggest the occurrence of DNA damage events via ROS-induced oxidation or mediated by decline in hTERT mRNA expression.

Carvacrol, a phenolic monoterpene found in essential oils of plants of the Lamiaceae family, emerges as an alternative acaricide of plant origin. Its acetylation was proposed to obtain a derivative compound with a better pharmacological profile and lower toxicity to non-target organisms. The present study aimed to assess the preclinical safety of acetylcarvacrol after dermal application in Wistar rats, through the examination of hematological and biochemical parameters, as well as histopathological analysis of the skin, liver and kidney. For this, twenty rats were distributed into four groups with five animals each. Three groups received treatment with different concentrations of the substance (26, 52, and 104 µL/mL) based on the lethal concentration for Rhipicephalus sanguineus ticks, and one group (Control) received only the vehicle. Acetylcarvacrol was applied daily to a trichotomized skin area for 21 days. No changes in hematological parameters were observed. Regarding biochemical analysis, a slight increase in urea and alanine transaminase levels was noted. No significant changes were observed in the kidney and liver, although the rats had developed cumulative irritant contact dermatitis at the application site, as corroborated by the histopathological analysis of the skin. In general, the results showed that the dermal application of acetylcarvacrol in the experimental conditions described here is safe. However, it can cause signs of mild systemic toxicity and skin irritation at high concentrations, suggesting that this product should be used in lower therapeutic doses and that the development of less aggressive formulations, including the combination with other acaricides, is desirable.

Numerous studies in Iraq have attempted to determine blood cholinesterase (ChE) activities with varying results in agricultural workers and veterinarians exposed to pesticides. This meta-analysis answers the specific inquiry of whether or not blood ChE activities decrease in agricultural workers exposed previously to pesticides. The meta-analysis included 14 records of blood ChE activities extracted from 12 studies after employing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). These records comprised ChE activities in agricultural workers exposed to pesticides (n = 635) versus their respective control cohorts (n = 416). We employed the one-group random effects model for the meta-analysis and the Newcastle-Ottawa Scale (NOS) to examine study quality. The combined effect size of pesticides exposed group (% ChE activity versus control) was significant at 86.13 %. Heterogeneity (I² = 49.86 %) was moderate. Subgroup analysis of the enzyme source (plasma/serum and erythrocytes/whole blood) revealed that plasma effect size was significant at 82.36 % compared to erythrocytes (92.08 %), which was not significant. No publication bias existed. The studies were of high quality (NOS ≥ 7). The present study is the first meta-analytic report of associating reduced blood ChE activities with pesticides exposure in Iraqi agricultural workers. Reduced pseudo ChE (plasma, serum) activity was the most significant indicator of pesticides exposure. Nevertheless, we recommend biomonitoring erythrocyte and even whole blood ChE activities in pesticides-exposed individuals, because of scarce information on the type and frequency of pesticides employed by Iraqi agricultural workers. Our findings call for a national integrated plan and improved regulations for safer and judicious pesticides applications and follow-up practices in Iraq in order to reduce potential health hazards and environmental risks.