Toxicology Research最新文献

The incidence of acute organophosphate (OP) poisoning has steadily increased in developing countries. Many studies showed that oxidative stress could have a significant role in its mechanism. The current study aimed to evaluate the role of N acetylcysteine (NAC) as an antioxidant in acute OP poisoned. A randomized, controlled, parallel-group trial was conducted in the period from the beginning of January 2022 to the end of June 2022. The study included 56 acute OP poisoned patients admitted to the intensive care unit (ICU) at the Poison Control Center of Ain Shams University Hospitals within 6 h after the exposure. The patients were randomly allocated in two equal groups; group (A): received the standard treatment plus NAC in a total dose of 300 mg/kg administered intravenously (IV) while group (B) received the standard treatment. Then both groups were compared as regards clinical parameters, laboratory investigations, ECG, and outcomes. Baseline parameters were comparable between the groups. However, NAC treatment significantly elevated concentrations of both serum catalase and glutathione peroxidase levels at 24 h, it did not significantly affect the total dose of atropine required, duration of atropine and oximes treatment or need for mechanical ventilation, and length of hospital stay. Mortality was lower in the NAC group (2 out of 28) than the standard treatment-only group (5 out of 28) but the difference was not statistically significant. This trial found that NAC improved antioxidant enzyme levels including serum CAT and GPX but did not affect clinically relevant outcomes.

Aluminium phosphide poison become an alarming, well-known, effective suicidal poison with a high mortality rate. There is a need for a simple tool that can triage patients with bad prognosis. The study aimed to assess the accuracy of ejection fraction as a predictor of mortality and morbidity in acute aluminium phosphide toxicity cases. The study involved 70 cases of acutely aluminium phosphide-poisoned patients in our hospital from January 2021 to January 2024. The study found that 54.3% of the cases were males and 45.7% were females, with a mean age of 22.4 ± 11.8 years old. The oral route was the route of administration of all cases, and the intention of poisoning was intentional in 84.3% of cases. Regarding the outcome of patients, 62.9% of the cases recovered, and 37.1% died. The Receiver Operating Characteristic Curve found that the ejection fraction below 37.5% had an accuracy rate of 96.8% with excellent discrimination for mortality, sensitivity of 100%, specificity of 93.2%, positive predictive value of 89.6%, and negative predictive value of 100%. The ejection fraction below 52.5% had an accuracy rate of 89% with good discrimination for complications, sensitivity of 83.3%, specificity of 96.8%, positive predictive value of 90.9%, and negative predictive value of 93.7%. So, the ejection fraction plays an essential tool in predicting mortality and complications in acute aluminium phosphide toxicity and should be assessed on every patient in the first 24 h of admission to facilitate the triage of these patients.

Our study focused on the potential mechanism of microRNA-490-3p (miR-490-3p) on learning/memory disability of rats resulting from sevoflurane (Sev). The rat model of cognitive dysfunction was established by infection with miR-490-3p mimic and Sev-exposure. Morris water maze and open field test assay were used for the assessment of cognitive deficits. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction assays were used for the measurements of neuroinflammatory cytokines and inflammatory-related genes in respective order. Bioinformatics analysis was employed for the predictive miR-490-3p-related genes. The targeted interaction was verified via dual-luciferase reporter assay. A significant decline of miR-490-3p was discovered in rats with Sev treatment, while the levels were up-regulated in rats with infection miR-490-3p pretreatment (P < 0.001). For Sev-induced rats, the stay time in the target quadrant was shorten, while distance travelled lengthened significantly with the control group by comparison (P < 0.001). Notably, an increased time of the escape latency and a decreased number of platform crossings were found in the Sev group, which alleviated by infection with miR-490-3p mimic pretreatment (P < 0.001). Moreover, the neuroinflammatory cytokines were elevated in the Sev group, the effects of which were recovered via miR-490-3p pretreatment (P < 0.001). Bioinformatics analysis predicted the miR-490-3p-associated genes. CDK1 (Cyclin-dependent kinase 1) was a potential target gene of miR-490-3p, which confirmed by dual-luciferase reporter detection. MiR-490-3p alleviated the learning and memory deficits in Sev-treated rats via the modulation of CDK1.

Acute aluminum phosphide (AlP) poisoning is one of the leading causes of suicide, particularly in the developing world. In cases of scarce and/or high-cost resources, it is advisable to prioritize critically ill patients who will benefit from available resources and improve their prognosis. Despite numerous scores, a dependable, easy-to-use, and quick approach to assessing the degree of poisoning is lacking. This study is designed to compare the prognostic performance of the National Early Warning Score 2 (NEWS2) versus the new-poisoning mortality score system (new-PMS) for predicting the clinical outcomes, including in-hospital mortality, vasopressor use, and mechanical ventilation placement after acute AlP poisoning. This study was a retrospective observational study that included patients with acute AlP poisoning with retrieving the required data from the patients' medical records. A total of 90 acutely AlP-intoxicated patients were enrolled in the study. The in-hospital mortality rate was 42.2%. Additionally, in-hospital mortality, vasopressor use, and mechanical ventilation placement were significantly higher in patients with higher NEWS2 and new-PMS scores. The new-PMS showed excellent prognostic performance, particularly in-hospital mortality prediction; however, NEWS2 demonstrated a more helpful predictive performance compared to the new-PMS particularly for the need for mechanical ventilation and in-hospital mortality, with an area under the curve of 0.991 versus 0.851 and 0.949 versus 0.874, respectively. We concluded that NEWS2 and new-PMS are simple, easily calculated, and lab-independent scoring systems. The NEWS2 is a more effective tracking and triggering tool than the new-PMS in the evaluation of AlP acutely intoxicated patients.

Polybrominated diphenyl ethers (PBDEs) have been classified as a new class of persistent organic pollutants by the United Nations Environment Programs in 2009. In environment, PBDEs can undergo the degradation process to form less brominated diphenyl ethers. In the present study, the 96 h LC₅₀ value for 4-bromodiphenyl ether (BDE-3) was found to be 3.18 mg/L in zebrafish embryo-larvae. Further, zebrafish embryo-larvae was exposed to sublethal concentrations i.e. 0.79 mg/L and 1.59 mg/L of BDE-3 to evaluate the developmental toxicity. BDE-3 significantly increased the mortality rate and decreased hatchability rate in a concentration and time-dependent manner at sublethal concentrations compared to control. Heart rate was found to be significantly decreased whereas the sinus venosus- bulbus arteriosus (SV-BA) distance found to be significantly increased in both BDE-3 exposed groups. The sensorimotor response and spontaneous movement were significantly decreased in BDE-3 exposed larvae compared to control group. A significant DNA damage was also found to be caused in BDE-3 exposed groups after the acute exposure. The current report highlights the toxicity potential of BDE-3 in the early life stages of zebrafish and hence puts up to their environmental risk assessment.

Aclonifen is a diphenyl ether herbicide being included in the list of priority substances. Nevertheless, the data related to its sublethal effects on fish are limited. Therefore, the present study has been carried out to investigate the toxic effects of aclonifen in juvenile Oncorhynchus mykiss following 24, 48, 72 and 96 hours of application to sublethal concentrations of 12.7, 63.5 and 127 μg/L. The application resulted in altered blood biochemistry appearing as hyperglycemia, decreased cholesterol and induced activities of transaminases of ALT and AST. The inhibition of AChE in brain, gill and liver was unimportant revealing its weak potential as anticholinesterase. The induction recorded for SOD, CAT, GPx and GST activities was accompanied with sustained elevation in TBARS and PC levels. It demonstrates both the pro-oxidant potential of aclonifen and oxidation of lipid and proteins resulting in the loss of membrane integrity and protein function. Hyperglycemic condition and decreased protein levels in gill and liver might be proposed as general adaptive responses to compensate increased energy demand. The integrative assessment of multi-biomarker responses shows concentration and duration related rise in calculated indexes. CAT, PC and SOD achieved the maximum scores for brain, gill and liver, respectively. Considering the results, oxidative stress inducing potential and weak anticholinesterase activity along with its disturbing impact on blood biochemistry were evidenced. Moreover, adverse affects observed after short term application on O. mykiss, present the potential risk aclonifen may cause at population level in aquatic ecosystems emphasizing the importance of pesticide regulations to avoid adverse impacts on non-target species.

Ginkgo biloba extract (GBE), a therapeutic drug, has anti-inflammatory and antioxidant effects that protect cells from harmful substances. Although GBE has been extensively studied in the prevention and treatment of lung diseases, its mechanism of action in chronic obstructive pulmonary disease (COPD) is unclear. In the present study, cigarette smoke extract (CSE) and cigarette smoke (CS) were used to induce COPD in cell and animal models. The expression of related genes and proteins was detected, and cell damage and lung tissue damage were evaluated via CCK-8 assays, flow cytometry analyses, ELISA, and HE staining. In HBE cells, the expression of miR-3,619-5p was upregulated after CSE induction. However, GBE treatment alleviated the impact of CSE on HBE cell damage and alleviated COPD in vivo. In addition, GBE treatment increased the expression of GPX4 by inhibiting the expression of miR-3,619-5p, and it reduced the release of the IL-6, IL-8, and TNF-α inflammatory factors. Moreover, GBE treatment decreased the production of ROS and MDA, as well as decreased the expression of the ferroptosis-related protein ACSL4, and it promoted the production of GSH and the expression of FTH1. Further, GBE treatment improved cell viability, inhibited ferroptosis, and ultimately alleviated COPD. The present findings suggest that GBE alleviates the progression of COPD through the inhibitory effect of the miR-3,619-5p/GPX4 axis on the ferroptosis process and that GBE may be an effective treatment option for COPD.

Kombucha is fermented and produced with a biofilm called a symbiotic culture of bacteria and yeast, which is drunk all over the world for its beneficial effects on human health and energy levels. The metagenomic study of kombucha frequently detected microorganisms in proteobacteria, firmicutes, and actinobacteria. And also, yeast and fungi are Ascomycota and Basidiomycota is present in green leaf and sugarcane juice fermented kombucha. The kombucha extracts' biological activities were assessed using pH, total phenolic content, antioxidant, antibacterial, and anticancer activity. Fermentation may enhance biological activity and the generation of bioactive substances. These results showed the pH -3.1 ± 0.2 and TPC -0.721 μg/mL of gallic acid equivalent. The antioxidant radicals scavenging activity of kombucha was evaluated by DPPH, ABTS, H₂O₂ and TAC. The bioactive chemicals identified by FT-IR and HR-LC/MS analysis of Kombucha totaled 45 components. The identified compounds were further move on to perform molecular docking study against gastric cancer target proteins 4H9M, 2DQ7 and 1TVO are binding with Nequinate compounds showing best LibDock scores 105.12, 114.49, and 108.97. So, this study suggests that knowledge can potentially active bioactive compounds are present in kombucha and it's stimulated the mechanism of gastrointestinal transit. Additionally, the metagenomic analysis gives strength to understand the bacterial and fungal distribution and its molecular mechanism from Kombucha.

Background: Rapid industrialization globally has led to a notable increase in the production and utilization of metals, including cadmium (Cd), consequently escalating global metal pollution worldwide. Cd, characterized as a persistent environmental contaminant, poses significant health risks, particularly impacting human health, notably the functionality of the kidneys. The profound effects of Cd stem primarily from its limited excretion capabilities and extended half-life within the human body. Mechanisms underlying its toxicity encompass generating reactive oxygen species (ROS), disrupting calcium-signaling pathways and impairing cellular antioxidant defense mechanisms. This review focuses on the protective effects of various herbal active ingredients against Cd-induced nephrotoxicity.

Aim: This study aims to investigate the mechanisms of action of herbal active ingredients, including ant-oxidative, anti-inflammatory and anti-apoptotic pathways, to elucidate potential therapeutic strategies for reducing nephrotoxicity caused by Cd exposure.

Methods: A comprehensive search of scientific databases, including Web of Science, PubMed, Scopus and Google Scholar, used relevant keywords to identify studies published up to October 2024.

Results: Research illustrates that herbal active ingredients protect against Cd nephrotoxicity by reducing oxidative stress, enhancing antioxidant enzyme activity, inhibiting inflammation, preventing apoptosis, alleviating endoplasmic reticulum (ER) stress, enhancing autophagy and improving mitochondrial function in the kidney.

Conclusion: The present study indicates that an extensive understanding of the protective effects of herbal active ingredients holds promise for the development of innovative approaches to safeguard human health and environmental integrity against the detrimental effects of Cd exposure.

Purpose: There is controversy about the effect of mercury (Hg) exposure on developing diabetes and insulin resistance. This study aimed to assess the risk of diabetes and insulin resistance in car painters using biochemical markers and serum Hg levels.

Methods: A retrospective case-control study involving 210 male participants aged between 25 and 50 years. The participants were divided into two groups: Car painters for at least one year and healthy people who had not worked as car painters and had no health concerns or chronic diseases.

Results: The serum levels of Hg, MDA (malondialdehyde), interleukin (IL)-1β, visfatin, fasting insulin, and fasting blood glucose (FBG) were evaluated. Serum Hg levels were significantly higher in car painters compared to the control group (19.00 ± 7.20 vs. 8.339 ± 3.916 μg/L, P-value < 0.001). Serum levels of visfatin, MDA, insulin, FBG, and IL-1β were significantly higher in the car painter compared to the control (P-value < 0.001). There was a significantly higher proportion of people with diabetes in car painters compared to control (8.6% vs. 0%) and higher prediabetic (30.5% vs. 13.3%, P-value < 0.001). In car painter workers, levels of Hg were significantly higher in DM compared to prediabetic and normoglycemic car painter workers (27.01 ± 1.59, 23.98 ± 4.31, and 15.39 ± 6.41 μg/mL, respectively, P-value < 0.001); additionally, levels of Hg were significantly higher car painter with insulin resistance compared to non-insulin resistance workers (21.18 ± 7.29 vs. 16.79 ± 16.7 μg/mL, P-value < 0.001).

Conclusions: Increased serum Hg in car painters increases the risk of insulin resistance and diabetes/prediabetes status.