Journal of Toxicology最新文献

Flourensia cernua DC, commonly known as hojasen or tarbush, is a medicinal plant used in arid regions due to its therapeutic properties, especially in the treatment of gastrointestinal disorders. This study aimed to assess the toxicity of a polyphenolic extract obtained from F. cernua. This research involved both in vitro (hemolytic and brine shrimp assay) and in vivo tests (acute oral toxicity) to determine the safety profile of this extract. The extract was obtained through a novel ultrasound-microwave extraction and purified by ion-exchange chromatography. Analysis of the polyphenolic extract revealed a rich composition of flavonoids and hydroxycinnamic acids, mainly apigenin glycosides. In toxicity tests, the polyphenols did not exhibit toxicity towards Artemia salina at a concentration of 1 mg/ml. Furthermore, incubation at 500 μg/ml for 4 hours showed a slight toxic effect on erythrocytes. In the acute oral toxicity test in mice, doses of 300 mg/kg and 2000 mg/kg did not result in animal mortality, indicating that the LD₅₀ exceeds 2000 mg/kg. However, the higher dose induced signs of toxicity, including lethargy, drowsiness, piloerection, and a significant decrease in weight during the initial two days postadministration of the polyphenolic extract. In addition, histological analysis suggested potential kidney damage at the 2000 mg/kg dose. According to OECD guidelines, while the extract can be classified as category 5 (low acute toxicity) due to the absence of mortality at 2000 mg/kg, the observed signs of toxicity should be considered in the overall risk assessment. These findings highlight the potential of F. cernua in pharmaceutical and nutraceutical applications due to its high polyphenolic content. However, further investigations are necessary to explore the specific effects of the compounds present in the extract. In addition, continuous evaluation of its long-term toxicity is essential to fully understand the extract's safety profile and efficacy.

Background: People who are addicted to amphetamines have a much greater chance of developing psychosis compared to those who are not. It is essential to study the behavioral and psychological effects of amphetamines. Therefore, this research aimed to examine conditions such as depression, anxiety, mood, cognitive abilities at the workplace, and social responsibilities by using sociodemographic factors as useful tools in determining effective strategies for preventing, managing, and treating amphetamine addiction.

Methods: A cross-sectional study among addicts hospitalized at two rehabilitation centers across Saudi Arabia between May and October 2023. A validated questionnaire consisting of psychiatric disorders assessment tools was distributed to healthcare professionals to start an interview with addicts to assess the abnormalities. The results were compared with healthy people (control). The assessment tools used are Hamilton Anxiety and Depression Rating Scale, Young Mania Rating Scale, and Work and Social Adjustment Scale. The data were analyzed using SPSS version 22.0. Pearson correlation coefficients (r) were employed.

Results: A total of 60 subjects participated in this study. The participants were divided into two groups (n = 60): group I was control (n = 25) healthy volunteers and group II was amphetamine abusers (n = 35), who were hospitalized for detoxification. The ages ranged from 18 to 60 years old with mean ages of 38.68 (±8.14) and 37.77 (±10.95) years in the control and amphetamine groups, respectively. Among the addicts, the mean severity dependence scale value was 10.46 (±1.82), which denotes high dependency on the illicit drug. The prevalence of high levels of anxiety, depression, and bipolar disorder was significantly higher among addicts when they were compared to healthy people (control). The assessment of the Work and Social Adjustment Scale (WSAS) reflected a higher impairment that minimized their ability to perform the work requirements, home management, social leisure, and relationships.

Conclusions: The addiction to amphetamines was associated with high impairment of work performance and social obligations and a negative impact on the addict's mental health. The risk of suffering anxiety, depression, and bipolar is higher than in nonaddict people. These effects are attributed to brain damage, neurotoxicity, and neuronal inflammation, particularly when these substances are abused over extended periods and at higher doses.

Liver impairment caused by VCM has been linked to irreversible damage such as fibrosis, necrosis, hepatocellular carcinoma, and liver angiosarcoma. However, the ability to detect abnormalities during initial phase have not been achieved so far. Thus, this study aimed to investigate the effect of interleukin 8 (IL-8) and C-X-C chemokines 2 (CXCR2) on screening for a VCM-exposed group (n = 227) from a PVC manufacturing factory compared to a control group (n = 110) in Tianjin City in 2020 with influence factors evaluation. Ambient concentrations of VCM and health archives from 2012 to 2018 were collected for establishing the dose-effect trend. A cross-sectional survey in 2020 was performed to measure TDGA, IL-8, CXCR2, 8-OHdG, SOD, GPX, CAT, MDA, and ROS levels. Results indicated a continuous increased incidence on liver abnormalities despite a fluctuated downward trend in cumulative time-weighted average (C_TWA) VCM concentrations over the years. ALT, AST, and AST/ALT ratio all contributed to liver abnormalities that contained fatty liver, liver calcification, and liver cysts, IL-8 and CXCR2 correlated with each other strongly and showed significant associations with oxidative stress markers, even AST/ALT ratio. IL-8 (>1547 µg/m³) or CXCR2 (<139 µg/m³) influenced the AST/ALT ratio through reciprocal interactions under oxidative stress injury, CXCR2 (>222 µg/m³), working years of 21 to 30 (a) and 11 to 20 (a), TDGA (>1.52 mg/L), alcohol consumption, smoking habit, and a less sleeping duration of <4 h per day would also be potential factors affecting the AST/ALT ratio. In conclusion (1) even with decreased VCM concentrations in PVC manufacturing factories liver abnormalities that contained fatty liver, liver calcification, and liver cysts could still occur due to oxidative stress injury with involvement of IL-8 and CXCR2. The status of protective measure and appropriate mask types also play a role; (2) the AST/ALT ratio could be a specific indicator for detecting abnormalities when combined with liver B ultrasonography results before impairment altered from bad to worse; and (3) factors such as definite medication history, fully broken protective facilities, alcohol consumption, less sleeping duration, inappropriate mask types, and longer working years could also influence AST/ALT ratio alterations through complex interactions.

The study aims to investigate the residual and histopathological effects of chronic aluminum chloride (AlCl₃) toxicity in the kidney and liver of male rats. After 30-, 60-, and 90-day exposure period, analyses were conducted to assess the toxicity in the kidney and liver. The results showed that the concentration of AlCl₃ in the kidney and liver increased significantly in 30-, 60-, and 90-day periods. The effects of oxidative stress on the kidneys and liver were dose- and time-dependent. Levels of malondialdehyde (MDA) significantly increased when exposed to AlCl₃ groups. Conversely, the activity of antioxidant parameters, including reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), significantly decreased in the AlCl₃ exposed groups, indicating compromised oxidant mechanisms. Both the kidney and liver exhibited severe tissue damage, including necrosis, fibrosis, and inflammatory cell infiltration, in rats exposed to AlCl₃. Kidney sections showed hyperplasia of the epithelial cells lining the renal tubules, resembling finger-like structures. Liver sections displayed severe lobular hyperplasia and an increase in mitotic figures. Our study suggests that AlCl₃ has a detrimental impact on these vital organs and emphasizes the importance of monitoring and mitigating aluminum exposure, particularly where it is present in high concentration.

PM_2.5 and arsenic are two of the most hazardous substances for humans that coexist worldwide. Independently, they might cause multiple organ damage. However, the combined effect of PM_2.5 and arsenic has not been studied. Here, we used an animal model of simultaneous exposure to arsenic and PM_2.5. Adult Wistar rats were exposed to PM_2.5, As, or PM_2.5 + As and their corresponding control groups. After 7, 14, and 28 days of exposure, the animals were euthanized and serum, lungs, kidneys, and hearts were collected. Analysis performed showed high levels of lung inflammation in all experimental groups, with an additive effect in the coexposed group. Besides, we observed cartilaginous metaplasia in the hearts of all exposed animals. The levels of creatine kinase, CK-MB, and lactate dehydrogenase increased in experimental groups. Tissue alterations might be related to oxidative stress through increased GPx and NADPH oxidase activity. The findings of this study suggest that exposure to arsenic, PM_2.5, or coexposure induces high levels of oxidative stress, which might be associated with lung inflammation and heart damage. These findings highlight the importance of reducing exposure to these pollutants to protect human health.

Curcuma xanthorrhiza Roxb, Phyllanthus niruri L., and Morinda citrifolia L. are Indonesian medicinal herbs used empirically as traditional therapeutics for maintaining health. The cocktail extract of these three plants (CECPM) had been developed and demonstrated immunostimulant activity in rats. This study aimed to evaluate the acute and subchronic toxicity of CECPM in vivo. The acute toxicity assay was conducted by orally administering a range dose of CECPM (313, 625, 1250, 2500, or 5000 mg/kg body weight (bw) on female mice once and then evaluating the toxic symptom every day for 14 days later. The chronic toxicity test was carried out by giving various doses of CECPM (600, 800, and 1000 mg/kg·bw) to female and male rats orally continuously for 90 consecutive days. The signs of toxicities were evaluated at the 90- and 28 days postadministration. The acute oral toxicity assays showed that there was no toxic syndrome and mortality found during the period of the experiment. The lethal dose level (LD₅₀) of CECPM was more than 5000 g/kg, which was categorized as practically non-toxic. Meanwhile, in the sub-chronic toxicity study, some parameters tested at 90 days postadministration and after 28 days of withdrawal, such as the body weight, relative organ weight, food intake, hematological and biochemical blood parameters, and also histopathological examination of five primary tissues (heart, liver, kidney, spleen, and lung) revealed no abnormalities. There was no-observed adverse effect level (NOAEL) for the present study of CECPM 1000 mg/kg·bw of the rat. Therefore, it is concluded that the orally administered CECPM was relatively nontoxic during acute and subchronic toxicology studies.

Previous studies showed that bisphenol-A (BPA), a monomer of polycarbonate plastic, is leached out and contaminated in foods and beverages. This study aimed to investigate the effects of BPA on the myogenesis of adult muscle stem cells. C2C12 myoblasts were treated with BPA in both proliferation and differentiation conditions. Cytotoxicity, cell proliferation and differentiation, antioxidant activity, apoptosis, myogenic regulatory factors (MRFs) gene expression, and mechanism of BPA on myogenesis were examined. C2C12 myoblasts exposed to 25-50 µM BPA showed abnormal morphology, expressing numerous and long cytoplasmic extensions. Cell proliferation was inhibited and was accumulated in subG1 and S phases of the cell cycle, subsequently leading to apoptosis confirmed by nuclear condensation and the expression of apoptosis markers, cleaved caspase-9 and caspase-3. In addition, the activity of antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase was significantly decreased. Meanwhile, BPA suppressed myoblast differentiation by decreasing the number and size of multinucleated myotubes via the modulation of MRF gene expression. Moreover, BPA significantly inhibited the phosphorylation of P65 NF-κB in both proliferation and differentiation conditions. Altogether, the results revealed the adverse effects of BPA on myogenesis leading to abnormal growth and development via the inhibition of phospho-P65 NF-κB.

Background: Since 2010, several cases of a new vasculopathy induced by the use of levamisole-adulterated cocaine (LAC) have been reported. This vasculopathy is characterized by retiform purpura, earlobe necrosis, multisystem compromise, and multiple autoantibodies. Given its similarity to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, LAC-associated vasculopathy is postulated to be mediated by pathophysiologic processes resulting from neutrophil cell death by NETosis, a phenomenon previously described in ANCA vasculitis. This study tries to establish the presence of NETosis induced by cocaine, levamisole, or both. Methodology. Neutrophils were isolated from the peripheral blood of healthy controls by Ficoll-Hystopaque density gradient centrifugation followed by dextran sedimentation. Cell viability and purity were evaluated by flow cytometry after staining with PI/DiOC6 and labeling with fluorescent anti-CD45/anti-CD3 monoclonal antibodies (mAbs), respectively. Neutrophils were exposed to levamisole, cocaine, a cocaine-levamisole mixture, and sera pools from healthy controls and patients with LAC-associated vasculopathy. NETosis was then assessed by flow cytometry after staining cells with Sytox Green, Hoechst-33342, and fluorescent antineutrophil elastase (NE) and antimyeloperoxidase (MPO) mAbs. In addition, NETosis was morphologically confirmed by fluorescence microscopy. Proinflammatory cytokine levels in culture supernatants and reactive oxygen species (ROS) synthesis were determined by flow cytometry. The involvement of calcium and muscarinic receptors in cell death induction was evaluated in parallel experiments carried out in the presence of 1,2-bis (o-aminophenoxy) ethane-N, N, N', N'-tetraacetic acid (BAPTA) and hyoscine butylbromide (HBB), their respective inhibitors.

Results: Cocaine, levamisole, and a cocaine-levamisole mixture induced neutrophil cell death. DNA/MPO extrusion and cell morphology patterns were consistent with NETosis. Neither proinflammatory cytokines nor ROS behaved as proNETotic factors. Preliminary results suggested that muscarinic receptors and calcium-dependent signals were involved in LAC-induced NETosis.

Conclusions: Cocaine, levamisole, and a cocaine-levamisole mixture can induce NETosis through mechanisms involving muscarinic receptors and calcium-dependent pathways.

It is well known that cigarette smoking adversely affects human health and induces oxidative stress in most vital organs. This study aims to assess the biochemical, histological, and ultrastructural values of honey and garlic extracts in ameliorating the effects of short-term exposure to cigarette smoke in mice. Forty-eight mice were randomly divided into six equal groups: group I was exposed to fresh air only, group II was exposed to cigarette smoke, group III was given 0.2 ml of honey extract, group IV was exposed to cigarette smoke and was given 0.2 ml of honey extract, group V was given 0.2 ml of garlic extract, and group VI was exposed to cigarette smoke and was given 0.2 ml of aqueous garlic extract. These exposures were repeated daily for 21 consecutive days among the treated groups. By the end of the third week, the animals were euthanized by physical cervical dislocation. Blood was taken for biochemical study, and the selected organs of the liver, kidney, and jejunum were processed for histological and ultrastructural studies. The biochemical results showed that short-term exposure of experimental mice to cigarette smoking did not alter the liver function tests except for decreasing the albumin level. Moreover, cigarette smoking elevates the concentration of carbonyl protein content and cystatin C. Histologically, the use of honey and garlic showed good protection to the liver, kidney, and jejunum, which was proved by transmission electron microscopy, in addition to lowering the oxidative stress biomarkers. In conclusion, using honey and/or garlic helps protect the liver, kidney, and jejunum against the hazardous effects of cigarette smoke.

Antiretroviral therapy (ART) has revolutionized the lives of people living with HIV/AIDS by overall improving their quality of life and increasing life expectancy. However, ART-associated hepatotoxicity and metabolic disorders in HIV/AIDS patients are growing concerns to clinicians, especially due to the long-term use of the drugs. This study reported on the phytochemical and pharmacological profile of hydroethanolic extracts of Piper nigrum stem (PNS) and evaluated its protective effect against tenofovir/lamivudine/efavirenz (TLE)-induced hepatotoxicity and dyslipidemia in Wistar rats. Cytotoxic, antioxidant, and anti-inflammatory assays were performed on PNS. Thirty-six rats divided into 6 groups of 6 animals/group were administered: distilled water, 17 mg/kg TLE, 17 mg/kg TLE and 100 mg/kg silymarin, 17 mg/kg TLE, and Piper extract (200 mg/kg, 400 mg/kg, or 800 mg/kg) orally for 28 days. The body weight of animals was recorded every 7 days. On Day 29, the rats were sacrificed, and blood samples were collected for hematological and biochemical tests. Portions of the liver and kidneys were collected for histological evaluation, while liver homogenates were prepared from the rest to measure antioxidant enzymes. PNS possessed in vitro cytotoxic, antioxidant, and anti-inflammatory activities. A significant decrease (p < 0.05) in the body weight of rats treated with PNS was observed. A significant high platelet count (p < 0.05) was observed in the PNS800 mg/kg group. A considerable decrease in alkaline phosphatase and triglycerides was observed in the silymarin and PNS group compared to the TLE-only group. The findings also show a significant increase in catalase and glutathione in the TLE-only group compared to the normal group, while SOD decreased. Histological observations revealed normal hepatic and renal tissues in the silymarin, and PNS-treated groups compared to the normal control, while leucocyte infiltration was observed in the TLE-only group. These results suggest that PNS extract possessed antioxidant activity that alleviated TLE-induced toxicity. Further studies are necessary to understand the pharmacokinetic interactions between ART and PNS.