Journal of Toxicology最新文献

Background: The synergistic activity of compounds in herbal drugs has been well established by multiple scientific studies. The compounds present in plants may have increased toxicity and increased efficacy. Owing to the notion that traditional medicines do not have any adverse effects, these are used heftily. Aim: The present study was designed to assess the toxicity of an herbal drug consisting of Asparagus racemosus roots, Tinospora cordifolia stems, and Trigonella foenum-graecum seeds extract blend (ATTEB), which is widely employed as an antimicrobial, anti-inflammatory, immunomodulator, adaptogen, female tonic, galactagogue, etc. Methodology: The current study evaluated its safety by acute (OECD 423) and subacute (OECD 407) repeated-dose toxicity studies. A phytochemical investigation was carried out and revealed the presence of principal bioactive constituents. A genotoxicity study was performed by micronucleus assay. Gross necroscopy of the animals was performed, and behavioral, hematological, biochemical, and histopathological studies were performed. Results: In the acute toxicity study, there was no mortality and no significant changes in behavior, organ structure, or organ weight, as observed by gross necroscopy of the animals, at a single dose of 2000 mg/kg BW. In a 28-day repeated-dose toxicity study, up to a daily dose of 1000 mg/kg BW, there was no evidence of toxicity. No significant genotoxicity was observed in the mice. Conclusion: The LD₅₀ found to be greater than 2000 mg/kg BW with NOAEL at 1000 mg/kg BW in mice. It was found to be free from any genotoxicity. The herbal drug was found to be safe to level of category 4 and can be used further for clinical studies.

Background: Drug poisoning is the most common type of poisoning in the world. The utilization of tramadol for the management of pain has been identified as a significant contributor to the incidence of poisoning cases. Tramadol poisoning can result in a range of neurological complications, including seizures and a decreased level of consciousness. Tramadol-induced seizures are frequently dose independent and manifest as generalized tonic-clonic seizures. The neurotoxic effects of tramadol are primarily manifested within the initial 24 h period following ingestion, with 84.6% of the seizures occurring within the first six hours. In addition, it has been documented that 15%-35% of the patients with tramadol poisoning have experienced seizures. The present study was undertaken to elucidate the clinical and paraclinical signs and symptoms observed in patients with tramadol poisoning and their correlation with the occurrence of seizures. Methods and Materials: All patients hospitalized due to tramadol poisoning from October 2019 to September 2020 in the poisoning department of Imam Reza Hospital if they met the inclusion criteria were studied. The patients were divided into two groups with and without seizures. The occurrence of seizures was substantiated through the documentation of EMS personnel and the direct observation of the attending physician in the emergency room. Following admission, the patient's blood glucose level was quantified via a glucometer. A blood sample was also obtained for subsequent laboratory evaluation. In the event of any aberrations in blood glucose levels, a re-evaluation was conducted at one-hour intervals using a glucometer. All findings were analyzed using SPSS Version 25 statistical software. The level of significance was set at p < 0.05. Results: A total of 163 patients were included in this study. In 94 patients (57.3%), some degree of consciousness loss and seizures occurred in 69 patients (42.1%). There was a significant relationship between the occurrence of seizures and the increase in blood glucose levels of patients (p=0.031). The findings indicated that 60% of the patients with blood glucose levels exceeding 140 mg/dL experienced seizures. Conclusion: Seizures in tramadol poisoning may be related to the patient's blood glucose levels.

The environmental xenobiotic aluminum chloride (AlCl₃) destroys reproduction via free radicals. The present study aimed at evaluating the impact of purple and white eggplant on rat fertility when exposed to AlCl₃. A total of 36 male albino rats were divided into six groups: a negative control, the second given AlCl₃ (17 mg/kg b.w.) for 28 days, the third and fourth given a basal diet with 5% and 10% white eggplant powder, and the fifth and sixth given a basal diet with 5% and 10% purple eggplant powder. AlCl₃ reduced follicular-stimulating hormone (FSH), plasma testosterone, sperm count, motility, and viability, luteinizing hormone (LH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities. On the contrary, malondialdehyde (MDA) and tumor necrosis factor alpha (TNF-α) disclosed considerable increases. Besides, reproductive hormones, antioxidant enzymes, and sperm quality were significantly enhanced in the treated groups with eggplants. A downregulation in the expression of Fkbp6, Ccna1, and Cyp19A1 was detected, and normal expression was restored after treatment with high dose from eggplant (10%) without significant differences, whereas Msh4 and Cdk2 genes continued in their down expression and measured decrease up to 60% in Msh4 and 40% in Cdk2 in their mRNA levels after treatment with high dosage from eggplant, respectively. Alternatively, rats treated with eggplant at high dose (10%) gained more body weight (33%) and much bigger testicles (1.30 ± 0.05 g) when compared to AlCl₃-treated rats (gained only 16% more body weight and 1.04 ± 0.06 g testis weight) after 28 days, subsequently, the eggplant reduced the side effect of AlCl3-induced toxicity. AlCl₃ induced broad cytotoxic effects in seminiferous tubules, and the antioxidant and anti-inflammatory activities of eggplant minimized the histological alteration in rat testes.

Background: Crude oil, a major key economic driver in developing countries, is also of environmental concern, linked to neurotoxicity and behavioural problems. Despite the known neurotoxic effects of crude oil and the potential benefits of zinc and vitamin E, there is a paucity of research specifically addressing their combined efficacy in mitigating neurochemical changes and behavioural deficits induced by crude oil. Current studies have largely focussed on the individual effects of these supplements in different contexts, but their synergistic potential in a crude oil exposure model remains underexplored. This study investigated the potential effects of zinc and vitamin E on neurobehavioural alterations in male Wistar rats fed with Bonny light crude oil (BLCO)-contaminated diet. Methods: Thirty (30) male Wistar rats (160 ± 10 g) were assigned into five groups (n = 6). Group 1 received standard rat feed, Group 2 was exposed to BLCO (0.1 mL/g of rat feed) for 3 weeks, and groups 3-5 were treated with zinc (50 mg/kg/day), vitamin E (400 IU/kg), or both [vitamin E (400 IU/kg) + zinc (50 mg/kg/day)], respectively for 1 week after BLCO exposure for 3 weeks. Locomotive, anxiolytic, depressive-like behaviours and spatial memory were assessed using the open-field test, elevated plus maze, forced swim test and Y-maze. Rats were sacrificed and the brain samples were collected for biochemical assays at the end of the behavioural tests. Results: Zinc and vitamin E supplementation (individually or combined) significantly increased brain total antioxidant capacity and superoxide dismutase (SOD) activity, reduced inflammatory markers (TNF-alpha) and lipid peroxidation, normalized neurotransmitter levels in the brain and improved behavioural performance. Conclusion: Treatment with Zn and/or vitamin E reverses BLCO-induced neurobehavioural alterations via modulation of oxidative stress, inflammation and neurotransmitters.

Plants are important components in sustaining the life of humans and animals, balancing ecosystems, providing animal feed and edible food for human consumption, and serving as sources of traditional and modern medicine. However, plants can be harmful to both animals and humans when ingested, leading to poisoning regardless of the quantity consumed. This presents significant risks to livestock health and can impede economic growth. In several developing countries, including Ethiopia, traditional communities have depended on medicinal plants for treating livestock and human diseases. The incidences of livestock poisoning from medicinal and poisonous plants are due to the misuse and lack of dosage standardization. Therefore, this paper aimed to review toxic plants and their effects on livestock health and associated economic losses. Toxic plants contain secondary metabolites that serve as a defense mechanism against predators. The most common secondary metabolites of toxic plants that affect livestock health and the economy include alkaloids (Asteraceae, Convolvulaceae, Lamiaceae, Fabaceae, and Boraginaceae), cyanides (Sorghum spp. and grass spp.), nitrates (Pennisetum purpureum roots, Amaranthus, nightshades, Solanum spp. Chenopodium spp., and weed spp.), oxalates (Poaecea, Amaranthaceae, and Polygonaceae), and glycosides (Pteridium aquiline). The most common effects of toxic plants on livestock health include teratogenic and abortifacient (Locoweeds, Lupines, Poison Hemlock, and Veratrum), hepatoxicity (Crotalaria, Lantana camara, Xanthium, and Senecio), photosensitization (L. camara, Alternanthera philoxeroides, Brachiaria brizantha, and Heracleum sphondylium), and impairing respiratory and circulatory systems (nitrite and cyanide toxic). Toxic plants lead to substantial economic losses, both direct and indirect. Direct losses stem from livestock deaths, abortions, decreased milk quality, and reduced skin and hide production, while indirect losses are associated with the costs of treatment and management of affected animals. Overall, toxic plants negatively impact livestock health and production, resulting in significant economic repercussions. Therefore, it is crucial to prioritize the identification of the most prevalent toxic plants, isolate secondary metabolites, conduct toxicity tests, standardize dosages, and develop effective strategies for managing both the toxic plants and their associated toxicity.

Lead, a heavy metal, has emerged as one of the most significant pollutants, bearing irreversible consequences on human and animal health in conjunction with industrial development. Presently, the use of medicinal plants to alleviate the adverse effects of heavy metal toxicity has captured the attention of researchers. Hence, the objective of this study was to assess the impact of levamisole and broccoli extract on the electrophoretic pattern of serum proteins, hematological parameters, and histopathological alterations in the liver, kidney, and spleen tissues within a lead poisoning model of rats. This experimental investigation spanned 28 days, involving 42 male Wistar rats categorized into seven groups: a control group, a lead acetate (AL) group administered at 1000 ppm in drinking water, a broccoli (B) group at 300 mg/kg/day, a levamisole (LE) group at 2.5 mg/kg/day, and combination groups of lead and broccoli (AL + B), lead and levamisole (AL + LE), and lead, broccoli, and levamisole (AL + LE + B). Upon completion of the study, hematological and biochemical parameters were assessed, and serum protein concentrations were analyzed using electrophoresis. Liver, kidney, and spleen tissues were fixed and subjected to histopathological examination with H&E staining. The findings indicated a significant decrease in white blood cells (WBC), red blood cells (RBC), and hemoglobin (Hb) levels in the AL group compared to other groups (p < 0.01). Conversely, the B group exhibited a notable increase in RBC and WBC compared to the AL group (p < 0.05). The most pronounced lead-induced damage was observed in the liver, resulting in elevated levels of specific enzymes such as AST and ALT in the AL group, accompanied by a decline in albumin and total protein (p < 0.001). A reduction in globulin levels, including Beta-2 globulin, was noted in the AL + B and AL + LE groups compared to the AL group (p < 0.001,  p < 0.05). Histopathological findings also unveiled increased infiltration of inflammatory cells and hemorrhage in the liver tissue, followed by the spleen, significantly higher in the AL group compared to other experimental groups (p < 0.05). Additionally, congestion and inflammation were evident in the spleen tissue compared to other groups. These tissue damages were mitigated in other combination treatment groups. Based on the aforementioned results, the combination of broccoli and levamisole is deemed effective in ameliorating liver and spleen injuries caused by lead and enhancing biochemical parameters and serum proteins.

Research on citrus plants is the result of increasing interest in the discovery of plant species with potential insect-repellent properties. Insect-repelling ability can be achieved by the numerous ubiquitous citrus species. This is mainly due to the presence of phytochemicals such as limonene, citronellol, citral, and α-pinene. These phytochemicals' composition varies depending on the geographical location of the plant. The extraction method dictates the configuration of attainable phytochemicals while the dosage affects the repellency potential. Therefore, developing insect repellent involved a number of observations related to the identification of both citrus plant phytochemical composition present in the different parts of the plant and the repellency potential of these phytochemicals in advance. Conversely, the development of repellent methods that go beyond conventional methods has been made possible by scientific developments including modern strategies such as encapsulation, the preparation of emulsion, and the incorporation of repellents into textiles. Therefore, this review article intends to probe into the aforementioned information and provide a sound insight into citrus-based repellent development in the future.

LN19183 is a standardized composition of Citrus aurantifolia (Christm) Swingle (CA) fruit rind and Theobroma cacao L. (TC) seed extracts that have recently been demonstrated to increase resting energy expenditure (REE) and reduce body fat in rats. CA and TC are important herbs in traditional medicine for various health benefits. The present study evaluates the comprehensive toxicity of LN19183 in acute, subchronic, and genetic toxicity studies following the guidelines of the Organization for Economic Co-operation and Development (OECD) for testing chemicals. The acute oral and dermal and 90-day subchronic oral toxicities were performed in rats, and acute dermal and eye irritations were performed in rabbits. In the subchronic toxicity study with a 28-day recovery period, male and female Sprague Dawley rats were orally gavaged with daily LN19183 doses of 500, 1000, or 2000 mg/kg body weight (BW). Furthermore, the genetic toxicity studies included mutagenicity in bacteria, chromosome aberration, and micronucleus assays in human blood mononuclear cells in vitro and micronucleus assay in Swiss albino mice bone marrow in vivo. Acute and subchronic repeat dose oral toxicity studies showed no adverse events, clinical signs, or mortality. All animals exhibited normal food and water intake and natural BW gain. In the 90-day study, LN19183 did not induce major changes in hematology, biochemical evaluations, and urine analysis; gross and histopathological findings did not show any treatment-related lesions or abnormality. The no observed adverse effect level (NOAEL) of LN19183 supplementation was 2000 mg/kg BW/day. In the genetic toxicity studies, LN19183 treatment did not show significant increases in the revertant bacterial colonies, chromosomal aberrations, or number of micronucleated cells. The present observations affirm that oral consumption of LN19183 is safe, and this botanical composition is nonmutagenic and nonclastogenic.

This study aimed to determine the levels of some heavy metals in the Koche River and the potential health risks. A replica of water samples was taken from 12 sampling sites purposely selected in the dry season. Heavy metal levels were determined using a flame atomic absorption spectrophotometer following the APHA (1998) procedure. Heavy metal pollution index (HPI), heavy metal evaluation index (HEI), chronic daily intake (CDI), hazard quotient (HQ), hazard index (HI), total hazard index (THI), and incremental lifetime cancer risk were calculated on the basis of the results. The heavy metals detected were Fe > Mn > Cu > Zn > Cr. The Cr, Fe, Mn, and Cu contents were above the maximum allowed limit of WHO for drinking and irrigation water at most of the sampling sites. The HPI and HEI values also surpassed the maximum limit of the study sites. The highest HPI and HEI values were found at the Yam1site. Oral ingestion represented 99.55% and 97.85% of CDI_total (CDI_ingestion + CDI_dermal contact) in adults and children, respectively. The mean CDI_total and the noncarcinogenic risk values were found in the order of Fe > Mn > Cu > Zn > Cr in both ages. CDI, HQ, HI, and THI scores were higher in children. The HI_oral and THI values were also higher than 1 in both ages except in DK 2, Sour 1, and Sour 2 sites. However, the HQ_dermal level was higher than 1 only for Cr in children. The ELCR obtained also indicated a high carcinogenic risk of Cr (0.75 ± 0.44 and 1.15 ± 0.66 in adults and children, respectively). In general, most of the study sites had heavy metal pollution levels that exceeded the maximum allowed limit. Therefore, effective management of sources of pollution and continuous monitoring of river quality to minimize health risks are very important.

The protective effect of Fe against Cd-induced toxicity in the liver and kidney of rats during concurrent administration of both metals was investigated in this study. Fifty female rats (130-150 g) were distributed into five groups of 10 rats each (n = 10): Group I (control), received normal saline solution; Group II (1.2 mg CdCl₂/kg b.w.); Group III (1.2 mg CdCl₂ + 0.25 mg FeCl₂/kg b.w.); Group IV (1.2 mg CdCl₂ + 0.75 mg FeCl₂/kg b.w.); and Group V (1.2 mg CdCl₂ + 1.5 mg FeCl₂/kg b.w.). Administration of both tested substances lasted for 47 days. Cd was injected intraperitoneally once a week, while Fe was administered to the Cd-exposed animals by oral gavage thrice weekly. The animals were killed at the end of the study, their blood was collected, and their liver and kidneys were harvested for biochemical and histological analysis. Following Cd administration, the kidney and liver showed a significant increase in Cd concentration, while Fe concentration in the kidney decreased. However, cotreatment with Fe decreased Cd concentration in the kidney and liver and increased Fe concentration in the kidney but not the liver, and the effect was more pronounced in the higher than lower doses. In the kidney, cotreatment with Fe especially at higher doses inhibited Cd-induced lipid peroxidation and plasma uric acid concentration. In the liver, lipid peroxidation which Cd did not alter was found to be elevated after cotreatment with the highest dose Fe. Inflammatory cell infiltrations of the central vein and renal tubular and glomeruli injury induced by Cd were not obviated by Fe cotreatment. It seems that both tissues respond differently to the concurrent administration of these metals and that Fe protected the kidney against oxidative injury-induced by Cd but not histopathological changes in both tissues.