Journal of Toxicology最新文献

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.

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.

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.

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.

Background: Cadmium (Cd) can contaminate aquatic environments as a result of anthropogenic activity. Cd accumulates quickly in the tissues of fish and has the potential to affect their physiology, including osmoregulation and acid-base balance. Therefore, the purpose of this study was to examine the sublethal effects of Cd on the osmoregulation and acid-base balance of tilapia Oreochromis niloticus at different times.

Methods: Fish were exposed to sublethal concentrations of Cd (1 and 2 mg/L) for 4 and 15 days. At the end of the experiment, fish were collected from each treatment to examine the levels of Cd and carbonic anhydrase (CA) in the gills, plasma osmolality, ions, blood pH, pCO₂, pO₂, and hematological parameters.

Results: Cd concentrations in gills rose with increasing Cd concentrations in the medium and exposure time. Cd inhibited respiration by generating metabolic acidosis, decreasing gill CA, reducing pO₂, plasma osmolality, Cl^-, and K⁺, particularly at 2 mg/L for 4 days and 1 and 2 mg/L for 15 days. Red blood cell (RBC), hemoglobin (Hb), and hematocrit (Ht) levels decreased as Cd levels in water and exposure duration increased.

Conclusion: Cd inhibits respiration, lowers RCB, Hb, and Ht levels and decreases ionic and osmotic regulation. All of these impairments can limit a fish's ability to provide appropriate oxygen to its cells, hence diminishing its physical activity and productivity.

The tripeptide H-Gly-Pro-Glu-OH (GPE) and its analogs began to take much interest from scientists for developing effective novel molecules in the treatment of several disorders including Alzheimer's disease, Parkinson's disease, and stroke. The peptidomimetics of GPEs exerted significant biological properties involving anti-inflammatory, antiapoptotic, and anticancer properties. The assessments of their hematological toxicity potentials are critically required for their possible usage in further preclinical and clinical trials against a wide range of pathological conditions. However, there is so limited information on the safety profiling of GPE and its analogs on human blood tissue from cytotoxic, oxidative, and genotoxic perspectives. And, their embryotoxicity potentials were not investigated yet. Therefore, in this study, measurements of mitochondrial viability (using MTT assay) and lactate dehydrogenase (LDH) release as well as total antioxidant capacity (TAC) assays were performed on cultured human whole blood cells after treatment with GPE and its three novel peptidomimetics for 72 h. Sister chromatid exchange (SCE), micronucleus (MN), and 8-oxo-2-deoxyguanosine (8-OH-dG) assays were performed for determining the genotoxic damage potentials. In addition, the nuclear division index (NDI) was figured out for revealing their cytostatic potentials. Embryotoxicity assessments were performed on cultured human pluripotent NT2 embryonal carcinoma cells by MTT and LDH assays. The present results from cytotoxicity, oxidative, genotoxicity, and embryotoxicity testing clearly propounded that GPEs had good biosafety profiles and were trouble-free from the toxicological point of view. Noncytotoxic, antioxidative, nongenotoxic, noncytostatic, and nonembryotoxic features of GPE analogs are worthwhile exploring further and may exert high potentials for improving the development of novel disease-modifying agents.

Avicennia africana is an important ethnomedicinal plant that has long been used to treat malaria and several other diseases. Despite the plant's antimalarial and other therapeutic properties, there is limited evidence-based data on its potential toxicity. Hence, the purpose of the current study was to assess the safety of A. africana leaf ethanolic extract (AAE). The study was designed to ascertain the cytotoxic effects of the crude extract on red blood cells (RBCs) as well as the acute and subacute toxicity in Wistar albino rats in accordance with Organization for Economic Co-operation and Development (OECD) guidelines "Test No. 423" and CPMW/SWP/1042/99. The pulverized, shade-dried plant leaves were sequentially macerated with 70% ethanol to obtain the crude extract (AAE). The extract's cytotoxic activity (CC₅₀) against the uninfected human red blood cells (RBCs) was determined using the 3-(4,5-Dimethylythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. For the acute toxicity studies, the rats (male and female) were divided randomly into six groups of five rats (n = 5) and dosed orally once with the following dose levels: 100, 300, 1000, 3000, and 5000 mgkg^-1, p.o. of the extracted AAE, with the control group receiving only the vehicle. In the repeated dose toxicity studies, the rats (both sexes) were orally administered daily with AAE at 100, 300, and 1000 mgkg^-1 for 14 days. Rat body weights were measured, and blood samples were tested for haematological and biochemical markers. Internal organs like the heart, kidney, liver, and spleen were collected, inspected, and weighed, and histological examinations were performed. The median lethal dose (LD₅₀) value is greater than 5000 mgkg^-1 body weight, with no significant change in bodyweight or relative organ weight (ROWs) of the extract-treated groups or control group. The extract showed greater cytotoxicity activity (CC₅₀), which was >100 μg/mL, compared to the reference drug (artesunate).The dosage groups of 100 and 300 mgkg^-1bwt had neutrophilia and lymphocytopenia (p < 0.05). However, changes in these haematological parameters may not be dose dependent and could be stress related. All the serum biochemical markers studied in rats given AAE did not show any significant change (p > 0.05). Histopathological examination of internal organs of AAE-treated rats did not show any significant abnormalities resulting from the extract treatment compared to the control group. Based on the findings in the present study, the LD50 value of AAE was found to exceed 5000 mgkg^-1 in the acute toxicity test, while the no observed adverse effect level (NOAEL) in rats was 1000 mgkg^-1 p.o. In the sub-acute toxicity tests. Histopathological analysis revealed no morphological abnormalities in the vital organs.

In the present study, the presence of organophosphorus (OPs) and carbamates (CBs) residues in the pond water and cultured Pangas catfish (Pangasius pangasius) samples collected from Comilla and Mymensingh areas were detected and assessed for their potential health risks. A total of 100 samples from each category were analysed among which 17% of the pond water samples and 9% of the fish samples were detected contaminated with OP and CB residues. The pond water and fish samples were extracted by liquid-liquid extraction (LLE), quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction, and ultrasonic extraction, respectively, and analysed through gas chromatography tandem mass spectrometry (GC-MS/MS). Among the detected OPs, Dursban (chlorpyrifos) and dichlorvos were detected, while among CB pesticides, carbofuran and sevin (Carbaryl) were detected in fish muscle samples. The detected OP and CB residual levels were below than the maximum residue limits (MRLs). The risk assessment study indicated no potential health risks. However, the level of compliance should be maintained through proper monitoring and controlling the overuse of pesticides in agricultural fields for public health safety.