Journal of Toxicology最新文献

Background: Beta-blockers carry a high risk of potentially causing fatal poisoning if overdosed. We aimed to assess the clinical and epidemiological characteristics of patients with beta-blocker poisoning.

Methods: Patients were categorized based on the type of drug poisoning into propranolol, other beta-blockers, and the combination of beta-blocker groups, respectively. Demographic data, drug toxicity, and clinical, laboratory, and treatment information of different groups were compared.

Results: During the study period, 5086 poisoned patients were hospitalized, of whom 255 (5.1%) had beta-blocker poisoning. Most patients were women (80.8%), married (50.6%), with a history of psychiatric disorders (36.5%), previous suicide attempts (34.6%), and intentional type of exposure (95.3%). The mean ± SD age of the patients was 28.94 ± 11.08 years. Propranolol toxicity was the most common among different beta-blockers (84.4%). There was a significant difference in age, occupation, education level, and history of psychiatric diseases with respect to the type of beta-blocker poisoning (P < 0.05). We observed changes in the consciousness level and need for endotracheal intubation only in the third group (combination of beta-blockers). Only 1 (0.4%) patient had a fatal outcome in toxicity with the combination of beta-blockers.

Conclusion: Beta-blocker poisoning is not common in our poisoning referral center. Propranolol toxicity was most common among different beta-blockers. Although symptoms are not different among defined beta-blocker groups, more severe symptoms are observed in the combination of the beta-blocker group. Only one patient had a fatal outcome in the toxicity with the combination of the beta-blocker group. Therefore, poisoning circumstances have to investigate thoroughly to screen coexposure with combined drugs.

Background: Trimeresurus stejnegeri (T.s) accounts for most snakebites in southern China, which always leads to coagulation dysfunction. Coagulopathy due to venom is widely considered to be a characteristic phenomenon of the DIC-like syndrome. It is vitally important for first-line clinicians to improve this condition as soon as possible. However, clinical factors associated with coagulation function in Trimeresurus stejnegeri has not been well characterized yet.

Materials: Patients bitten by vipers were admitted to the Emergency Department of a hospital in Shenzhen, southern China, from 2021 to 2022 and were retrospectively reviewed. Patient clinical characteristics and laboratory data were compared in the eligible patients bitten by T.s by their prothrombin time (PT), fibrinogen level (FIB), and platelet count on 2-3 days after bitten.

Results: 105 patients were included in this study. The mean values of PT, FIB, and PLT are as follows: 12.8 ± 0.79 s, 2.25 ± 0.47 g/L, and 196.2 ± 57.1 × 10⁹/L. Uric acid (UA) (367.9 ± 103.85), blood glucose (6.53 + 1.64) show negative trend of correlation, while CRP (2.12 + 4.17) shows positive trend of association with coagulation function. The smoke and systolic blood pressure may exert negative effects on PT and PLT, respectively. Logistic regression analysis indicated that uric acid (UA) shows significant connection with PT (OR = 1.15 and P value <0.0001), FIB (OR = 0.89 and P value = 0.026), and PLT (OR = 0.79 and P value = 0.007). CRP is also shown to be associated with FIB (OR = 1.33 and P value = 0.043).

Conclusion: : Uric acid (UA) shows a significant association with PT, FIB, and PLT. CRP is related to FIB. Blood glucose shows a negative trend of correlation with PT. We do recommend physician should low the level of UA in some degree on the basis of injection of an antivenom serum.

Objective: It is well known that paclitaxel (PTX)-induced neurotoxicity seriously affects the quality of life of patients and is the main reason for reducing the dose of chemotherapy or even stopping chemotherapy. The current data are limited, and further information is required for practice and verification. The aims of this study were to clarify the molecular mechanism underlying PTX-induced neurotoxicity by combining in vivo and in vitro metabolomics studies and provide new targets for the prevention and treatment of PTX-induced neurotoxicity.

Methods: In the in vivo study, a PTX-induced neurotoxicity mouse model was established by intraperitoneal injection of PTX (6 mg/kg every three days) for two consecutive weeks. After verification by water maze tests and HE staining of pathological sections, hippocampal metabolites were measured and the differential metabolites and related metabolic pathways were identified by multivariate statistical analysis. In the in vitro study, we investigated the effects of PTX on mouse hippocampal neuron cells, assessing the concentration and time of administration by MTT assays. After modeling, the relevant metabolites in the TCA cycle were quantified by targeted metabolomics using stable isotope labeling. Finally, the key enzymes of the TCA cycle in tissues and cells were verified by RT-PCR.

Results: Administration of PTX to model mice resulted in neurological damage, shown by both water-maze tests and hippocampal tissue sections. Twenty-four metabolites and five associated metabolic pathways were found to differ significantly between the hippocampal tissues of the model and control groups. These included metabolites and pathways related to the TCA cycle and pyruvate metabolism. Metabolomics analysis using stable isotope labeling showed significant changes in metabolites associated with the TCA cycle compared with the control group (P < 0.05). Finally, RT-PCR verified that the expression of key enzymes in the TCA cycle was changed to different degrees in both hippocampal tissues and cells.

Conclusion: Our results showed that PTX neurotoxicity in hippocampal tissue and neuron cells was associated with inhibition of the TCA cycle. This inhibition leads to brain insufficiency and impaired metabolism, resulting in various neurotoxic symptoms.

The Niger Delta, Nigeria, is noted for crude oil exploration. Whereas there seems to be a handful of data on soil polycyclic aromatic hydrocarbon (PAH) levels in this area, there is a paucity of studies that have evaluated soil and vegetation PAHs simultaneously. The present study has addressed this information gap. Fresh Panicum maximum (Jacq) (guinea grass), Pennisetum purpureum Schumach (elephant grass), Zea mays (L.) (maize), and soil samples were collected in triplicate from Choba, Khana, Trans-Amadi, Eleme, Uyo, and Yenagoa. PAHs determination was carried out using GC-MS. The percentage composition of the molecular weight distribution of PAHs, the molecular ratio of selected PAHs for identification of possible sources, and the isomeric ratio and total index of soil were evaluated. Pennisetum purpureum Schumach (elephant grass) from Uyo has the highest (10.0 mg·kg^-1) PAH while Panicum maximum (Jacq) (guinea grass) has the highest PAH (32.5 mg·kg^-1 from Khana. Zea mays (L.) (maize) from Uyo (46.04%), Pennisetum purpureum Schumach (elephant grass) from Trans-Amadi (47.7%), guinea grass from Eleme (49.2%), and elephant grass from Choba (39.9%) contained the highest percentage of high molecular weight (HMW) PAHs. Soil samples from Yenagoa (53.5%) and Khana (55.3%) showed the highest percentage of HMW PAHs. The total index ranged 0.27-12.4 in Uyo, 0.29-8.69 in Choba, 0.02-10.1 in Khana, 0.01-5.53 in Yenagoa, 0.21-9.52 in Eleme, and 0.13-8.96 in Trans-Amadi. The presence of HMW PAHs and molecular diagnostic ratios suggest PAH pollution from pyrogenic and petrogenic sources. Some soils in the Niger Delta show RQ_(NCs) values higher than 800 and require remediation to forestall ecohealth consequences.

Global honeybee losses and colony decline are becoming continuous threat to the apicultural industry, as well as, for food security and environmental stability. Although the putative causes are still unclear, extensive exposure of bees to pesticides could be the possible factor for worldwide colony losses. This study was aimed at evaluating the impact of nine commonly used pesticide incidents on adult worker honeybees (A. mellifera) under the laboratory condition, in North Gonder of Amhara region, Ethiopia. Feeding test, contact test, and fumigation tests were carried out for each pesticide following the standard procedures, and each pesticide toxicity was compared to the standard toxic chemical, dimethoate 40% EC (positive control), and to 50% honey solution (negative control). The results revealed that all the tested pesticides caused significant deaths of the experimental bees (P < 0.05) in all the tests when compared to the negative control. Diazinon 60% EC, endosulfan 35% EC, and malathion 50% EC were appeared highly toxic causing 100% mortality of bees, while chlorsulfuron 75% WG killed 90% of the experimental bees as tested via feeding. On the other hand, agro-2, 4-D and its mixture with glycel 41% EC are moderately toxic, and mancozeb 80% WP and glycel 41% EC were slightly toxic to honeybees as compared to the positive control (dimethoate 40% EC). Suddenly, diazinon 60% EC and malathion 50% EC triggered 100% mortality of bees, while endosulfan 35% EC and chlorsulfuron 75% WG caused 63.63% and 90.82% of bee mortality, respectively, when evaluated via contact test. The fumigation test also showed that chlorsulfuron 75% WG, diazinon 60% EC, and endosulfan 35% EC caused 100%, 86.7%, and 65.6% mortality rate of bees. Our result also highlighted that tested LD₅₀ of all pesticide incidents were significantly lower than the manufacturer-based LD_50. This shows that local honeybees A. m. jemenetica are extremely sensitive to commonly used agricultural pesticides, which may affect the colony level due to the intensive application of these pesticides in Ethiopia.

Background: The product combination of Piper crocatum Ruiz. and Pav., Phyllanthus niruri Linn., and Typhonium flagelliforme (Lodd.) BL ethanolic extract (SKM) exerts immunomodulatory activity. However, the toxicity profile of the combination has never been investigated.

Objective: This study aimed to establish the acute toxicity profile of the SKM product on Sprague-Dawley (SD) rats and its subchronic toxicity profile on female SD rats.

Method: The acute and subchronic toxicity tests were conducted in accordance with OECD 423 and OECD 408, respectively.

Result: The SKM product was safe up to 5000 mg/kg b.w. in male and female SD rats. In repeated doses of SKM for 90 days, the administration of 22.5, 45, and 90 mg/kg b.w. per day of the SKM product to female SD rats did not affect clinical signs, body weight, food and water consumption, hematological parameters, clinical chemical parameters, urinalysis, relative organ weights, and gross pathological and histopathological features compared with the control group.

Conclusion: Analyses of these results suggest that the long-term oral administration of the SKM product for 90 days does not cause subchronic toxicity.

The heavy metal cadmium is extremely harmful to both humans and animals. Zinc supplementation protects the biological system and reduces cadmium-induced toxicity. This study aimed to determine whether zinc chloride (ZnCl₂) could protect male mice with the damaged liver induced by cadmium chloride (CdCl₂). The protective role of zinc chloride and expression of the metallothionein (MT), Ki-67, and Bcl-2 apoptotic proteins in hepatocytes were studied after subchronic exposure of mice to cadmium chloride for 21 days. Thirty male mice were randomly categorized into 6 groups (5 mice/group) as follows: a control group that did not receive any treatment, a group given ZnCl₂ at 10 mg/kg alone, and two groups received ZnCl₂ (10 mg/kg) in combination with CdCl₂ at two concentrations (1.5 and 3 mg/kg), while the last two groups received CdCl₂ alone at 1.5 and 3 mg/kg, respectively. Immunohistochemical examination revealed a decrease in Ki-67 expression in Kupffer and endothelial cells, which reflected cell proliferation downregulation accompanied by MT increased expression. However, the Bcl-2 was ameliorated and reduced to demonstrate an enhanced rate of necrosis rather than apoptosis. Furthermore, histopathological results showed significant alteration such as hepatocytes with a pyknotic nucleus, infiltration of inflammatory cells around the central vein, and the presence of many binucleated hepatocytes. Zinc chloride treatment resulted in histological and morphological improvements that were average in the expression of apoptosis proteins modifications induced by cadmium. Our findings revealed that the positive effects of zinc might be linked to the high metallothionein expression and enhanced cell proliferation. Furthermore, at low-dose exposure, cadmium-induced damage to cells could be more closely related to necrosis rather than apoptosis.

Schizophrenia is a chronic mental complaint known as cognitive impairment. There has been evidence that inflammation and oxidative stress play a main role in schizophrenia pathophysiology. This study aimed to investigate the effects of l-carnitine, as a potent antioxidant, on the treatment of behavioural and biochemical disturbances in mice with ketamine-induced schizophrenia. In this study, schizophrenia was induced in mice by ketamine (25 mg/kg/day, i.p). Before induction of schizophrenia, mice were treated with l-carnitine (100, 200, and 400 mg/kg/day, i.p). Then, behavioural impairments were evaluated by open field (OF) assessment and social interaction test (SIT). After brain tissue isolation, reactive oxygen species (ROS), glutathione concentration (GSH), lipid peroxidation (LPO), protein carbonyl oxidation, superoxide dismutase activity (SOD), and glutathione peroxidase activity (GPx) were assessed as oxidative stress markers. Furthermore, inflammatory biomarkers such as tumour necrosis factor alpha (TNF-α) and nitric oxide (NO) were evaluated in brain tissue. Our results showed ketamine increased inflammation and oxidative damage in brain tissue that was similar to behaviour disorders in mice. Interestingly, l-carnitine significantly decreased oxidative stress and inflammatory markers compared with ketamine-treated mice. In addition, l-carnitine prevented and reversed ketamine-induced alterations in the activities of SOD and GPx enzymes in mice's brains. Also, improved performance in OFT (locomotor activity test) and SIT was observed in l-carnitine-treated mice. These data provided evidence that, due to the antioxidant and anti-inflammatory effects of l-carnitine, it has a neuroprotective effect on mice model of schizophrenia.

Rhamnus prinoides is used as a traditional medicinal plant to treat pneumonia, sprain, gonorrhea, rheumatism, and ringworm infections as well as for the preparation of local beverages in Ethiopia. It has a widespread antioxidant, antimalarial, antimicrobial, wound healing, and anti-inflammatory activities. These activities are due to the presence of alkaloids, steroids, triterpenes, tannins, flavonoids, flavones, phenols, and glycosides. This study aimed to investigate acute and subacute toxicity of R. prinoides leaves on histopathology of the liver, kidney, and brain tissues, and biochemical profiles of rats. For the acute toxicity study, female rats were treated with R. prinoides at a dose of 5000 mg/kg body weight and followed-up for 14 days. In the subacute toxicity study, four groups of rats were used. The first three groups, respectively, received 250, 500, and 1000 mg/kg body weight of R. prinoides extract and the fourth group was a control group. Signs of toxicity, food intake, and weight was recorded. At necropsy, organ weight measurement and macroscopic and microscopic evaluations of the liver, kidney, and brain were carried out. Different clinical chemistry profiles of rats were also measured. Single-dose oral administration of R. prinoides extract at 5000 mg/kg produced no mortality indicating the LD₅₀ is greater than 5000 mg/kg body weight. A four week administration of R. prinoides extract did not bring deleterious outcomes on the food consumption and weight gain of rats. Moreover, gross examination, histopathological evaluation, and weight measurement conducted on the liver, kidney, and brain did not reveal treatment related changes. The biochemical analysis showed no significant difference between the treatment and control groups. Consumption of R. prinoides leaf for 4 weeks might not have a toxic effect in rats. However, further investigations upon long-term administration should be conducted to have a wider safety margin.