Journal of Toxicology最新文献

Imidacloprid (IMI) is a neonicotinoid insecticide used worldwide, either alone or in combination with other pesticides. The goal of this study was to assess the effects of IMI on the central nervous system of rats and its mechanism of oxidative stress-induced DNA damage by oxidant/antioxidant parameters. Fifteen male rats, divided into three groups, were used: the first group received 5 ml/kg body weight corn oil as a control, the second received a high oral dose of IMI (45 mg/kg body weight), while the third received a low dose (22 mg/kg body weight). After 28 days, acetylcholinesterase (AChE) activity, oxidative stress markers, histopathological alterations, and DNA damage were examined in the brains of these rats. The AChE activities decreased significantly after IMI exposure, reaching 2.45 and 2.75 nmol/min/mg protein in high dose and low dose, respectively, compared to the control group (3.75 nmol/g tissues), while the concentration of malondialdehyde MDA increased significantly (29.28 and 23.92 nmol/g tissues) vs. the control group (19.28 nmol/g tissues). The antioxidant status parameters such as reduced glutathione (GSH) content was 13.77 and 17.63 nmol/g, catalase (CAT) activity was 22.56 and 26.65 µmol/min/g, and superoxide dismutase (SOD) activity was 6.66 and 7.23 µmol/min/g in both doses against the control group (21.37 nmol/g, 30.67 µmol/min/g, 11.76 µmol/min/g), respectively, and histopathological changes in the brain tissues were observed. More in vivo research using epigenetic methods is needed to determine the ability of IMI and its metabolites to cause neurotoxicity and DNA lesions in mammalian brains.

Entomotoxicology is based on using insect evidence recovered from a dead body to find out the cause and time of the death. Drugs can accumulate in fly larvae when they ingest the flesh of deceased persons and alter the normal development of the fly causing implications in calculating postmortem intervals. Lorazepam is an antidepressant generally used to treat anxiety. Larvae of Chrysomya rufifacies were fed on the beef liver mixed with lorazepam to study the effect of lorazepam on the developmental rate of larvae and to count delay in postmortem interval. Larvae grown on the beef liver with different doses of lorazepam showed delayed development as compared to normal larvae. The life cycle durations in experimental cultures with different concentrations of lorazepam completed in 1 ppm (272.56 hrs), 2 ppm (289.23 hrs), 3 ppm (324.10 hrs), and 4 ppm (350.72 hrs), while in the control culture life cycle completed in 257.26 hrs. The length, weight, and width of the larvae treated with lorazepam were smaller than the untreated culture. Length, weight, and width decreased with increased concentration of lorazepam. This delay in development ultimately affects the postmortem interval. That is why prior knowledge of the life cycle of flies with respect to various drugs needs to be studied, and these baseline data can be used to calculate postmortem interval and cause of death.

Medicinal plants such as Senna italica are increasingly used for their purgative virtues to treat stomach aches, fever, and jaundice. This study aims to screen the phytochemical compounds and to assess the antioxidant activity in vitro and the acute oral toxicity in vivo of Senna italica leaves. The plant was harvested, dried, pulverized, and preserved. Phytochemical screening was performed using different laboratory protocols. Ethanolic and aqueous extracts were, respectively, obtained by maceration and decoction technics. The assay for free radical scavenging was used to examine the antioxidant activity using DPPH. Acute oral toxicity was performed with aqueous and ethanolic extracts at 5000 mg/kg of body weight on female albinos Wistar rats, weighing 152.44 ± 3.68 g. Subjects were checked for any signs of mortality and macroscopy toxicity during the 14 days of the study. Biochemical and hematological parameters were measured to assess liver and kidney functions, and histological analysis of these organs was conducted. Phytochemical analysis highlighted the presence of total phenols, flavones, tannins, alkaloids, and quinone derivatives. Semiethanolic (78 μg/mL), ethanolic (9.7 μg/mL), and aqueous extract (9.2 μg/mL) showed an interesting antioxidant activity. Biochemical and hematological parameters were normal and not significantly different (p > 0.05). The plant extracts did not produce any toxic effect or mortality at the provided dose. Senna italica extracts induced an increase in the volume of liver and kidney tissues but no necrosis. Thus, lethal dose 50 of Senna italica leaf extract is probably higher than 5000 mg/kg.

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.