Journal of Toxicology最新文献

Doxorubicin, an effective antineoplastic agent, is often prescribed for the treatment of various carcinomas. However, the use of doxorubicin becomes limited due to its adverse effects like cardiotoxicity, dysmenorrhea, and leucopenia. Cardiogrit Gold (CG) is a herbo-mineral Ayurvedic medicine prescribed for the treatment of various cardiovascular ailments. The current study aimed to investigate the therapeutic potential of CG in imparting protection against doxorubicin-induced cardiotoxicity. Wild-type (N2) and genetically modified Caenorhabditis elegans(SJ4005 and DA597) were used as model organisms to assess the bioactivity of CG against doxorubicin-induced cardiotoxicity. Chemical characterization of CG was performed by HPLC-based analysis. Calcium, a key mineral component of CG, was measured in CG-treated C. elegans using inductively coupled plasma mass spectrometry (ICP-MS) analysis, as the marker of CG internalization in C. elegans. Toxicity induced by doxorubicin and its recovery upon CG treatment was determined by various toxicologically important endpoints. CG treatment rescued N2 C. elegans from doxorubicin-induced reduction in their growth, reproduction, locomotory behavior, pharyngeal pumping, feeding ability, and increased ROS generation. CG treatment modulated the expression of hsp-4 in SJ4005 C. elegans suggestive of decreased ER stress and normalized the pharyngeal grinder damage in DA597 C. elegans, indicating a robust induction of cardio-normalcy. Novel analytical methods were developed to detect and quantify doxorubicin in C. elegans on HPLC and UPLC/QToF-MS platforms. Interestingly, CG treatment decreased bioaccumulation of doxorubicin in C. elegans, robustly correlating with the observed cardioprotective effects. Taken together, CG has a strong cardioprotective profile against doxorubicin-induced damages and could be taken for further preclinical and clinical assessments.

[This corrects the article DOI: 10.1155/jt/9857933.].

In response to the COVID-19 pandemic and following the World Health Organization's call for action, several traditional medicine recipes were used without any scientific prerequisites concerning their safety. The current study investigated several short-term toxicity parameters of SAYE PLUS, an antimalarial phytomedicine used in COVID-19 patients in Burkina Faso. Following the guidelines of the Organisation for Economic Co-operation and Development (OECD), the safety profile of SAYE PLUS was investigated in a battery of tests in rats and mice. In an acute toxicity study, male and female rats received a single oral dose of 2000 mg/kg b.w. of the test substance. For the subacute toxicity test, male and female rats received daily oral doses of 250, 500, and 1000 mg/kg b.w. for 28 days. Acute and subacute toxicity tests were accompanied by food and water intake, body and organ relative weight, and blood chemistry of animals recording. In mutagenicity, sperm quality, and lipid peroxidation tests, mice were orally exposed to daily oral doses of 500, 1000, and 2000 mg/kg for seven days. Single dose of 2000 mg/kg b.w. of SAYE PLUS did not cause rats mortality. The LD₅₀ is more than 2000 mg/kg b.w. Daily administration of SAYE PLUS for 28 days did not induce any significant change in the water or food intake and the body or organ relative weights of animals. Furthermore, no significant change was observed in biochemical parameters. In the test conditions, the recipe did not induce an increase of micronucleus or changes in sperm motility and number. However, all tested doses of SAYE PLUS induced a significant increase in MDA levels in mice serum. These results show that SAYE PLUS did not induce negative impacts on studied parameters, but the possible lipidic peroxidation observed must be further investigated for its mechanism and effects.

Copra meal hydrolysate (CMH) with high protein and mannooligosaccharides (MOS) was derived by β-mannanase hydrolysis. CMH has been shown to elicit health benefits via prebiotic properties. However, a systematic examination of its safety is required before effective utilization. This study assessed CMH oral acute toxicity at a single dose of 2000 mg/kg for 14 consecutive days, while a subacute toxicity test was conducted by daily oral administration of CMH at doses of 0.25, 0.5 and 1.0 mg/kg for 90 days using Sprague Dawley rats and following OECD guidelines 423 and 408. The acute toxicity study showed that the LD₅₀ of CMH was over 2000 mg/kg since no mortality or abnormal clinical signs were observed at this dose. The subacute toxicity results showed that CMH did not induce any abnormalities in body weight, food and water consumption, clinical signs, haematology, clinical chemistry, organ weight and necropsy. Significant changes in some of the parameters were observed but most were not treatment-related and had no effect on animal health. No toxicity-related microscopic findings were recorded in the examined tissues (lung, heart, liver, spleen and kidneys). Oral administration of CMH had a 'no observed adverse effect level (NOAEL)' of 1.0 mg/kg for both male and female Sprague Dawley rats. CMH demonstrated a high level of safety in animal studies and can be considered a safe prebiotic substance for use in the food and nutraceutical industries.

Consumption of aflatoxin-contaminated food is responsible for hepatotoxicity. Dichrocephala integrifolia (D. integrifolia) is used in traditional African medicine to treat various liver diseases. This study aimed to evaluate the therapeutic effects of aqueous leaf extract of D. integrifolia on aflatoxin-containing peanut-induced liver damage in Wistar rats. The animals were fed the standard diet (SD) or the SD supplemented with stored and poorly preserved peanuts (50:50) containing aflatoxins for 42 days. Then, animals received the diet concomitantly with D. integrifolia (100, 200 mg/kg), or Silybon 100 mg/kg for 14 days. At the end of the experimental period, biochemical markers, including the lipid profile, liver function markers, and proinflammatory markers, were evaluated. A histopathological analysis of the liver was performed. Semiquantitative evaluation of aflatoxin B1 in peanuts by thin-layer chromatography was carried out, and phytochemical characterization of the extract by high-performance liquid chromatography-mass spectrometry was performed. As a result, poorly stored peanuts contain 20 μg/kg aflatoxin B1/kg of peanuts. Consumption of contaminated peanuts resulted in inflammation characterized by a significant increase (p < 0.001) in proinflammatory cytokines (TNF-α, INF-γ, and IL-13) and a significant increase (p < 0.001) in transaminase activities, GGT, ALP, and levels of total bilirubin, total cholesterol, triglycerides, LDL cholesterol, and a significant decrease (p < 0.001) in HDL cholesterol and albumin levels. These various abnormalities were accompanied by a significant increase (p < 0.001) in oxidative stress. These disturbances were confirmed by hepatic cytolysis, leukocyte infiltration, and vascular congestion. Treatment with D. integrifolia extract at all doses tested reversed these abnormalities. These beneficial effects of the extract could be due to β-amyrin formate, identified in this extract, and could therefore justify the use of this plant extract in traditional medicine to manage liver diseases.

Bromophenols are synthesized chemicals that are widely used in various industrial activities and are also naturally produced by marine algae as secondary metabolites, including 2,4-dibromophenol (2,4-DBP), 2,6-dibromophenol (2,6-DBP), and 2,4,6-tribromophenol (2,4,6-TBP). However, the toxicological profiles and toxicity data of these bromophenols remain largely unreported, necessitating further investigation. Acute toxicity tests of 2,4-DBP, 2,6-DBP, and 2,4,6-TBP were conducted in this study using Scenedesmus quadricauda and Daphnia magna (standard tests). Furthermore, a modified acute toxicity test of D. magna was proposed, which further evaluates the dietary supplementation effects (1.0 × 10⁴ cells/mL of S. quadricauda) on the toxicities of these three bromophenols (modified tests). The median effect concentrations (EC₅₀s) of D. magna increased significantly when S. quadricauda was supplied as the dietary supplement. The EC₅₀ values of 2,4-DBP increased from 2.17 to 4.47 mg/L, 2,6-DBP from 2.78 to 6.75 mg/L and 2,4,6-TBP from 1.57 to 3.28 mg/L. Moreover, the web-based interspecies correlation estimation platform coupled with the species sensitivity distribution model (Web-ICE-SSD) was used to calculate the fifth percentile hazard concentrations (HC₅s) for 2,4-DBP, 2,6-DBP, and 2,4,6-TBP. The HC₅ values when using standard test data for 2,4-DBP, 2,6-DBP, and 2,4,6-TBP were 0.55, 0.71, and 0.43 mg/L, respectively. In contrast, the HC₅ values when using modified test data increased to 1.20, 1.80, and 0.88 mg/L. These results indicated that dietary supplementation during acute toxicity tests may provide more environment-related risk assessment.

Background: Glue inhalation is a common unconventional substance of abuse, and it contains neurotoxic and volatile solvents. We examined the toxicity profile and central nervous system (CNS) activities of glue inhalation in Wistar rats. Methods: Acute toxicity was investigated, and the subacute toxicity was studied using 24 male Wistar rats at graded concentrations of air, 2, 4 and 8 mL glue (n = 6/group) for 28 days. Blood samples were collected for biochemical and haematological evaluations, and vital organs (lung, liver, kidney, heart, brain and eye) were used for histological analysis. Behavioural studies were carried out using an elevated plus maze, hole board test, open-field test, tail suspension test and forced swim test. Dependence and abstinence effects were also evaluated. Results: The lethal dose (LD₅₀) of the inhalational glue was 14.14 mL. Glue significantly increased liver function parameters such as TB, DB, ALP, ALT, TP and electrolyte levels (K⁺ and HCO₃) but reduced cholesterol levels in exposed rats. Glue inhalation had significant anxiolytic and depressant effects on the rats at concentrations of 4 and 8 mL. Histological analysis revealed liver and lung tissue abnormalities and subconjunctival inflammation in eye tissue at 8 mL. Conclusion: The study therefore suggests that glue inhalation has anxiolytic and depressant effects in Wistar rats.

Fall armyworm (FAW), Spodoptera frugiperda (Smith) (Lepidoptera: Noctuidae), is a polyphagous pest, particularly destructive to maize crops all over the world. It is native to America but has strong flying capabilities, and currently, the FAW has invaded many Asian countries, including Pakistan. Therefore, the current study aims to monitor its activity in four different areas of Pakistan. The damage percentage was recorded in different fields of maize crops caused by FAW. Furthermore, the susceptibility test of four different pesticides was performed against FAW under laboratory conditions. Maximum damage was recorded in the autumn crops that were surrounded by other alternative hosts such as sorghum, potato, jantar, rice chilies, and cotton when compared to the spring crops (with no alternate host in their surroundings). Temperature seems to play an important role in the size of the FAW population and the damage they cause. The results showed that among the four tested insecticides, emamectin benzoate and lufenuron exhibited higher toxic effects, while chlorpyrifos and lambda-cyhalothrin showed lower toxicities against FAW. Additionally, the study revealed an increasing resistance of FAW populations to commonly used insecticides, especially in South Punjab. These findings underscore the urgent need for integrated pest management strategies to address resistance development. Despite the observed resistance, emamectin benzoate remains a viable control option, but proactive resistance management is crucial for its continued effectiveness in long-term FAW control.

The increasing popularity of herbal preparations has prompted people around the world to incorporate herbal products into their balanced diet, aiming to improve brain health and protect against neurological disorders. Erqember(Erq-Em) possesses a blend of various neuroprotective phytocompounds. The present study aimed to phytochemically analyze this polyherbal product and scientifically validate its neurological benefits. After chemical characterization through UHPLC-MS, in vivo studies involved the supplementation of mice with 10 and 20 mL/kg doses of Erq-Em in an AlCl₃-induced amnesic mice model followed by behavioral assessment for anxiety and cognition in a battery of behavioral tests. Subsequently, whole brains were dissected for biochemical and histopathological analysis. Further, the study also included in silico studies to understand the interaction of detected phytocompounds with acetylcholinesterase protein. The outcomes revealed that mice treated with Eqr-Em were protected from anxiety-like behavior as they dose-dependently prefer innately frightening central, lightened, and elevated zones in OFT, L/D, and EPM tests. Moreover, the Erq-Em supplementation caused improved spontaneous learning in Y-maze and NOR tests, while their memory in passive avoidance and water maze tests was evident from longer step-through and shorter escape latencies, respectively. The biochemical analysis of brain homogenates showed a reduction in AchE and MDA while elevation in SOD and GPx levels in mice receiving Erq-Em. Moreover, the healthy and intact neuronal counts were markedly high in CA1 and DG regions of Nissl's-stained hippocampi of Erq-Em-treated mice. The compounds detected by UPLC-MS showed favorable BBB permeability and interacted well with acetylcholinesterase protein through in silico studies. Overall, the neurological benefits of Erqember might result from enhanced cholinergic neurotransmission and antioxidative activity of its phytocompounds, which together function as multimodal strategies against AlCl₃-induced neurotoxicity.

Clarias gariepinus' (Burchell, 1822) early-stage development was assessed in microconcentrations of glyphosate-based herbicides (GBHs), Forceup, Roundup, and Uproot. Using the default ecological trigger value of 0.37 mg L^-1 of glyphosate as a reference, herbicides were diluted to microconcentrations containing 0.006, 0.013, 0.025, 0.05, and 0.10 ([v/v] %) of herbicide using borehole water, which served as control. Concentrations and control were replicated three times. Fertilization (%), time to morula formation and to commencement of hatching (minutes), hatching (% fertilized eggs), and 96-h larval survival (% hatched larvae) in microconcentrations were monitored. Within formulation, concentration significantly affected fertilization and hatching rates (p < 0.001), time to morula formation and hatching, and 96-h larval survival ([χ ²] 5 = 16,648, p = 0.010; [Kruskal-Wallis H test]). Morula formation, fertilization, hatching, and larval survival rates were significantly affected by formulation in Concentrations 2 and 3, while fertilization rate was significantly affected at all concentrations ([χ ²] 3 = 6.49, p = 0.039). The glyphosate ecological trigger value of 0.37 mg L^-1 as well as the recommended application rate of Roundup Proactive in aquatic and riparian environments of 0.32% (v/v) are higher than the lowest significant effect concentrations of the herbicides. Reactive oxygen species (ROS) and superoxide dismutase (SOD) in control embryos, were higher but not significantly, than levels in freshly stripped eggs (p > 0.05) (Mann-Whitney U test). Early-stage development was normal in controls, suggesting a balance between ROS and SOD. This was, however upset in treatments, leading to deleterious effects on early-stage development. GBHs pose a greater risk to fish reproduction, varying in severity with the formulation. This should be considered in regulations for their use in aquatic and riparian environments, balancing herbicide effectiveness with the risk of aquatic toxicity.