Toxicology Research最新文献

Objective: Alzheimer's disease (ad) is a progressive and degenerative disorder of the central nervous system that is associated with cognitive and memory impairment. The main factors which have been implicated in neurodegeneration of ad are oxidative stress and cholinergic neurons dysfunction. Here, we examined the effects of auraptene, a novel acetylcholinesterase (AChE) inhibitor, on hydrogen peroxide (H₂O₂)-induced cell death in PC12 cells.

Methods: Thereby, we measured cell viability, intracellular reactive oxygen species (ROS) production, AChE inhibitory activity, cell damage and apoptosis with AlmarBlue, 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA), Ellman method, lactate dehydrogenase (LDH) release, propidium iodide (PI) staining and western blot analysis, respectively.

Results: H₂O₂ (150 μM) resulted in the cell death and apoptosis while, pretreatment with auraptene (10, 20 and 50 μM) significantly increased the viability (P < 0.01), and at 5-50 μM decreased ROS amount (P < 0.05 and P < 0.001). Pretreatment with auraptene (10, 20 and 50 μM) lessened AChE activity (P < 0.001), and at 20 and 50 μM reduced the release of LDH (P < 0.001), and at (10, 20 and 50 μM) diminished the percentage of apoptotic cells (P < 0.001). Also, pretreatment with auraptene at 10,20 and 50 μM prevented from poly (ADP-ribose) polymerase (PARP) cleavage (P < 0.001), and cytochrome c release (P < 0.01 and P < 0.001). The amount of caspase 3 activity (P < 0.001) and survivin (P < 0.001) were elevated after pretreatment of cells with auraptene at 10-50 μM and 10 and 50 μM.

Conclusion: It seems that auraptene has the ability to slow down or stop H₂O₂-induced nerve cells death by reducing the activity of AChE and suppression of internal pathway of apoptosis.

Objective: Cadmium (Cd) and lead (Pb) are non-biodegradable heavy metals (HMs) that persistently contaminate ecosystems and accumulate in bones, where they exert harmful effects. This study aimed to investigate the protective effect of fucoxanthin (FX) against the chemical toxicity induced by Cd and Pb in human bone osteoblasts in vitro, using various biochemical and molecular assays.

Methods: The effect of metals and FX on osteoblasts viability was assayed by MTT, then the effect of Pb, Cd, and FX on the cells' mitochondrial parameters was studied via assays for ATP, mitochondrial membrane potential (MMP), mitochondrial complexes, and lactate production. Also, the effect of metals on oxidative stress was assessed by reactive oxygen species, lipid peroxidation and antioxidant enzymes assays. Also the effect of FX and metals on apoptosis caspases and related genes was assessed.

Results: When Cd and Pb were added to human osteoblast cultures at concentrations ranging from 1-20 μM for 72 h, they significantly reduced osteoblast viability in a time and concentration-dependent manner. The cytotoxic effect of Cd on osteoblasts was greater than that of Pb, with estimated EC50 of 8 and 12 μM, respectively, after 72 h of exposure. FX (10 and 20 μM) alleviated the cytotoxicity of the metals. Bioenergetics assays, including ATP, MMP, and mitochondrial complexes I and III activities, revealed that HMs at 1 and 10 μM concentrations inhibited cellular bioenergetics after 72 h of exposure. Cd and Pb also increased lipid peroxidation and reactive oxygen species while reducing catalase and superoxide dismutase antioxidant activities and oxidative stress-related genes. This was accompanied by increased caspases -3, -8, and - 9 and Bax/bCl-2 ratio. Co-treatment with FX (10 and 20 μM) mitigated the disruption of bioenergetics, oxidative damage, and apoptosis induced by the metals, showing a concentration-dependent pattern to varying extents.

Conclusion: These findings strongly support the role of FX in managing toxicities induced by environmental pollutants in bones and in addressing bone diseases associated with molecular bases of oxidative stress, apoptosis, and bioenergetic disruption.

Introduction: About 80% of patients receiving chemotherapeutics suffer from side effects related to the gastrointestinal tract. Irinotecan (CPT-11) is a chemotherapeutic agent usually used in treating solid tumors. Quercetin (QRT), a bioflavonoid, is an antioxidant and scavenger reactive oxygen species scavenger.

Objective: The current study explored the possible protective effects of QRT against mucosal tongue injury caused by CPT-11.

Methods: The study included four equal groups: group 1/control, group 2/QRT, group 3/CPT-11, and group 4/CPT-11 + QRT.

Results: CPT-11-induced tongue injury in the form of non-healed ulcers, absent lingual papillae, mononuclear cells infiltration, marked deposition of collagen fibers, and overexpression of CD86 and tumor necrosis factor- α (TNF-α). The increased malondialdehyde levels, decreased superoxide dismutase and total antioxidant capacity revealed that there was an oxidative stress. Also, there was a decreased countenance of Ki-67 and Bcl-2 and an increased countenance of NF-κB. The QRT-treated group showed complete ulcer healing, with histological features almost like the control group, along with minimal collagen fiber deposition, decreased reactivity to CD86 and TNF-α and improvement of oxidative stress status and the molecular study results as well.

Conclusion: QRT possess protective properties against CPT-11-triggered tongue injury.

A growing trend in understanding human health involves looking at the bigger picture by examining all potential environmental exposures that may cause health risks, with a particular focus on dietary intake of anthropogenic chemicals. This study investigated the presence of pesticide residues in honey and pollen samples collected randomly from ten locations in four agricultural governorates during the spring season of 2023 in the Nile Delta, Egypt. A QuEChERS extraction was employed for sample preparation before GC-MS analysis for pesticide residues. The human health risk associated with these residues were evaluated using hazard quotient (HQ). Our findings indicate that the detection rate and levels of pesticide residues are greater than previously reported. Giza governorate exhibited the highest content of residues in both honey and pollen samples, followed by El-Dakahlia, El-Qalyubia and Gharbia. Also, honey samples from El-Dakahlia, El-Qalyubia, and Giza contained the highest concentrations of aldrin, hexachlorocyclohexane (HCH) and chlorpyrifos, ranging from 10.45 to 19.6 μg kg ^-1 , 21.70 to 62.23 μg kg ^-1 , and 167.55 to 190.74 μg kg ^-1 , respectively. Pollen grain samples from Giza and El-Dakahlia showed high levels of chlorpyrifos (76.20 μg kg ^-1 ) and HCH (33.60 μg kg ^-1 ), respectively. Health hazard and quotient studies indicate that the residue levels of pesticides in all tested honey did not pose a significant risk for human consumption. Out of all pesticides, aldrin is the only one that requires further risk assessment to determine its potential impact on honeybee colonies.

Azo food dyes are prohibited in most countries, but their injudicious use is still reported particularly in the developing Nations. Continuous use of contaminated food raises health concerns and given this the present study designed to investigate the effects of 3 non-permitted azo dyes (metanil yellow - MY, malachite green - MG, and sudan III - SIII) on neurobehavioral, neurochemicals, mitochondrial dysfunction, oxidative stress, and histopathological changes in the corpus striatum of rats. Rats were grouped and treated with MY (430 mg/kg), MG (13.75 mg/kg), SIII (250 mg/kg) & mixture (YGR) (MY 143.33 + MG 4.52 + SIII 83.33 mg/kg) p.o. for 60 days showed a significant decrease in grip strength and motor activity, the activity of acetylcholinesterase (AChE), monoamine oxidase - B (MAO-B), and mitochondrial complex I and II compared to the control. The treated groups showed a significant increase in lipid peroxidation and a decrease in the level of reduced glutathione, superoxide dismutase, and catalase as compared to the control. Histopathology of the corpus striatum revealed immense damage. Data from the present study correlate between azo dyes and changes in the behavior of rats which have been associated with the altered biochemicals and neurochemicals activities. In conclusion, exposure to azo dyes caused neurotoxicity involving motor impairments associated with enhanced oxidative stress, mitochondrial dysfunctions, AChE and MAO-B inhibition, and neuronal damage in the corpus striatum of rats.

To investigate the role and mechanism of miR-342 and FOXP1 on hepatocellular carcinoma cells. QRT-PCR was applied to determine the expression of miR-342, FOXP1 and MYCBP in normal hepatocyte cell lines (NHC), hepatocellular carcinoma cell lines (HEK-293 T) and human hepatocellular carcinoma cell lines (HepG2, MHCC97-L, Huh7 and SMMC7721). After knockdown or over-expression of miR-342 and FOXP1 in HepG2 cells respectively, cell proliferation and cell viability were measured using MTT assay and colony formation assay. Flow cytometry was adopted to test for apoptosis. Dual luciferase gene reporter assays were performed to validate the target relationship between FOXP1and miR-342 or MYCBP. The level of apoptosis-related proteins cleaved-caspase-3, Bcl-2 and Bax were measured by western blot. Compared with NHC, miR-342 expression was decreased and FOXP1 expression was up-regulated in hepatocellular carcinoma cell lines. MiR-342 could target and negatively regulate FOXP1. FOXP1 could promote the proliferation of hepatocellular carcinoma cells, positively regulate the expression of c-Caspase-3, Bax, negatively regulate Bcl-2 and inhibit apoptosis. FOXP1 can also target and positively regulate MYCBP. The expression of MYCBP was up-regulated in the hepatocellular carcinoma cell lines, while overexpression of miR-342 decreased MYCBP expression promoted by overexpression of FOXP1. MiR-342 can inhibit FOXP1/MYCBP signaling axis to regulate the members of Caspase-3 and Bcl-2 family to inhibit the proliferation and promote apoptosis of hepatocellular carcinoma cells.

Background: Cyclophosphamide, an immunosuppressive alkylating agent, has been used against breast cancer, lymphoma and myeloid leukemia. Despite various therapeutic uses, its toxic impacts on multiple organs remains to be fully elucidated.

Aim: This study aimed to investigate dose dependent toxic impact of cyclophosphamide on liver, kidney, brain and testis emphasizing serum and tissue biochemical and histological alterations.

Materials and methods: Experimental design consisted of five groups of albino rats. Group 1-5 were administered vehicle for five consecutive days. On 6^th day, group 1 received vehicle only and termed as control; group 2-5 received cyclophosphamide through intraperitoneal route at the rate of 50, 100, 150 and 200 mg/kg dose, respectively. After 24 h of the last administration, rats were euthanised; serum and tissue biochemistry; histology, sperm count and its motility were performed.

Results: Serological, biochemical and histological indices exhibited dose dependent deviations from their regular status as a marker of toxicity in liver, kidney, brain and testis. Tukey's HSD post hoc test revealed maximum damage in multiple organs with 200 mg/kg dose of cyclophosphamide.

Background: Aluminum phosphides (AlP) is a solid fumigant pesticide known for its high toxicity and mortality. Diagnosis of AlP is based on the history and clinical examination. The literature on the early prediction of adverse outcomes following AlP exposure is limited. Therefore, the current study aimed to investigate the role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte Ratio (PLR) as early accessible predictors of mortality in AlP-exposed patients.

Method: We conducted a retrospective cross-sectional study on 420 adult patients with acute AlP poisoning.

Results: This study reported mean NLR and PLR of 4.07 ± 3.82 and 182.97 ± 147.29, respectively. Patients with high NLR and PLR showed more severe presentation, indicated by the significantly lower Glasgow scales and higher poison severity score grades. Besides, the need for mechanical ventilation, vasopressor therapy, and ICU admission was significantly higher among patients with high NLR and PLR (P = 0.000). We observed a significantly higher proportion of mortality among patients with high NLR (69.5%) and PLR (87.4%) (P = 0.000). The NLR > 3.42, PLR > 172.5, and their combinations were significant predictors of mortality, showing area under curves above 0.94. Utilizing a combination of NLR and PLR yielded a modestly improved performance as a mortality predictor with a slight increase in the Youden index (0.81). The high NLR and high PLR groups had mean survival times of 28.851 and 16.256 h respectively.

Conclusion: These findings suggest that high NLR and PLR are associated with a worse prognosis and a higher mortality risk among patients with acute AlP poisoning.

As the demand for fish increases, the amount of wastewater generated from fishponds is also increasing with potential environmental and public health effects from their indiscriminate disposal. This study aimed at comparative analyses of the physicochemical and heavy metal constituents and potential DNA damage by wastewaters from natural and artificial fishponds using Allium cepa assay. A. cepa were grown on 3.13, 6.25, 12.5, 25.0, and 50.0% (v/v; wastewater/tap water) concentrations of each wastewater. At 48 and 72 h, respectively, genotoxic and root growth inhibition analyses were carried out on the exposed onions. The onion root tips exposed to wastewaters showed a significant (P < 0.05) inhibition of root growth and cell division in a concentration-dependent manner. Additionally, chromosomal abnormalities like spindle disturbances, sticky chromosomes, micronucleus, bridges, and binucleated cells were observed in the exposed onions and their induction was higher significantly relative to the negative control. Generally, wastewater from the natural fishpond caused higher chromosomal aberrations than the wastewater from artificial fishpond. It is our belief that the cytotoxicity and genotoxicity observed in the onions were primarily caused by heavy metals like Cr, Cd, Fe, Pb, Cu, and Zn found in the wastewaters. These metals also showed a significant carcinogenic and non-carcinogenic risks in children and adults with Cd as the highest contributor to these detrimental risks. Ingestion route was the major exposure route to the toxic metals in these wastewaters. Wastewater from the natural fishpond showed a higher health risk than the wastewater from the artificial fishpond. These findings suggest that the wastewaters from natural and artificial fishpond contain compounds that might induce cytogenotoxicity in exposed organisms.

In this study, effects of vitaminB₁₂ on embryonic development have been investigated by supplying vitaminB₁₂ on a hypoxia-induced embryo culture. 9.5-day-old embryos from Wistar albino adult pregnant rats were used in our experimental set up.10 μM and 100 μM vitaminB₁₂ were added to culture medium which is then exposed to in vitro hypoxia. Additionally, 11.5-day-old embryos and yolksacs were examined morphologically. Different vitaminB₁₂ doses are compared within experimental groups. It was found that both control and experimental groups in 11.5-day-old embryos are at same developmental stage. It was also determined that oxygen deficiency influenced embryonic development and yolk sac vascularity in hypoxia group, are lagging behind in all experimental groups (P < 0.05). However, the development of vitaminB₁₂ embryos were similar to control group under normoxic conditions (P > 0.05). It was also observed that development was compensated through supplement of vitaminB₁₂ to hypoxia group (P < 0.05). It was indicated that the development in H + 100 μM vitB₁₂ groups was quite close to control group. However, development of H + 10 μM vitB₁₂ embryos were in parallel with hypoxic group. Furthermore, H + 100 μM vitB₁₂ group showed higher embryonic development than H + 10 μM vitB₁₂ group (P < 0.05).VitaminB₁₂ treatment has been used to prevent intrauterine growth restriction which can be caused by many different pharmacological agents. However, nobody has investigated effects of vitaminB₁₂ on hypoxia-induced early embryo growth retardation. In the light of our findings, administration of 100 μM vitaminB₁₂ restores damage of embryonic development due to hypoxia and this application also increases embryonic vascularity and circulation. Thus, supplementation of vitaminB₁₂ can be offered as a therapeutic approach towards cell death and diseases such as neurovascular and cardiovascular diseases and in the near future.