Drug and Chemical Toxicology最新文献

Podocyte injury is a major biomarker of primary glomerular disease that leads to massive proteinuria and kidney failure. Ginsenoside Rk1, a substance derived from ginseng, has several pharmacological activities, such as anti-apoptotic, anti-inflammatory, and antioxidant effects. In this study, our goal is to investigate the roles and mechanisms of ginsenoside Rk1 in podocyte injury and acute kidney injury (AKI). C57BL/6 mice were intraperitoneally injected with 10 mg/kg LPS to mimic AKI-like conditions in vivo. One hour after the LPS challenge, ginsenoside Rk1 (10 mg/kg or 20 mg/kg) or vehicle was orally administered into mice every 6 h until sacrifice at 24 h. Renal functions were assessed by measuring blood urea nitrogen and creatinine. Renal histological changes were examined by hematoxylin and eosin staining. The production of proinflammatory cytokines in kidney tissues was evaluated by RT-qPCR and western blotting. A conditionally immortalized mouse MPC-5 podocyte cell line was treated with LPS and ginsenoside Rk1. Viability and apoptosis of MPC-5 cells were estimated by CCK-8 and flow cytometry. Western blotting was also conducted to measure the protein levels of apoptosis-related and pathway-related genes. The results of abovementioned experiments revealed that Ginsenoside Rk1 ameliorated LPS-stimulated podocyte apoptosis in vitro and relieved renal dysfunctions and inflammatory response in LPS-induced AKI mice. Mechanistically, ginsenoside Rk1 inactivated the JAK2/STAT3 and NF-κB pathways in LPS-treated podocytes and mice. In conclusion, this study shows that Ginsenoside Rk1 attenuates LPS-induced renal dysfunctions and inflammatory response in mice and LPS-induced podocyte apoptosis in vitro through inactivating the NF-κB and JAK2/STAT3 pathways.

In the present study, the effects of coenzyme Q10 (CoQ10), which is widely used in daily life, on the methotrexate (MTX)-induced hepatotoxicity, which is widely used today in malignancies and autoimmune diseases, were examined. Twenty-four female Wistar albino rats were divided into four groups. The group 1 (n = 6) was given 1 mL corn oil by oral gavage (p.o.) during seven days. Group 2 was given 20 mg/kg intraperitoneal (i.p.) MTX only on the first day of the experiment. Group 3 was given 20 mg/kg (i.p.) MTX on the first day of the experiment and 100 mg/kg CoQ10 dissolved in 1 mL corn oil were given by oral gavage during seven days, and group 4 was given 100 mg/kg CoQ10 dissolved in 1 mL corn oil by oral gavage during seven days. At the end of experiment, all animals were euthanized under anesthesia. In the liver tissue, histopathologic analysis on the hematoxylin and eosin (H&E), Masson trichrome, and periodic acid Schiff (PAS) stained sections, apoptotic analysis (% Annexin V positivity) by flow cytometry, and biochemical analysis for oxidative stress markers (GSH, CAT, and TBARS) was performed. According to histopathological analysis, apoptosis, concession, fibrosis, and inflammatory cell infiltration increased in the MTX group and those results significantly decreased in the MTX + CoQ10 groups. As an interesting result, fatty degeneration and TBARS elevation were observed in the MTX + CoQ10 group. As a result, although CoQ10 has protective effects on MTX-induced hepatotoxicity, fatty degeneration due to the combined usage of MTX and CoQ10 should be investigated with further studies.

Polycyclic aromatic hydrocarbons (PAHs) are an organic chemical family produced during incomplete combustion of organic materials. Besides, PAHs are associated with different detrimental health effects. Therefore, this research was aimed to assess the association between PAHs exposure, metabolic syndrome (MetS) prevalence, and cardiovascular risk in a Mexican population. Urinary 1-hydroxypyrene (1-OHP) was the exposure biomarker quantified. MetS prevalence was defined using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and the International Diabetes Federation (IDF) criteria. Also, we used the atherogenic index of plasma (AIP) as a cardiovascular risk biomarker. The mean urinary 1-OHP level quantified was 2.50 ± 1.25 µmol/mol creatinine. The MetS prevalence found was 35% (n = 222) and 31% (n = 197) using NCEP ATP III and IDF criteria, respectively. The mean AIP value was 0.32 ± 0.15. Furthermore, the data analysis showed robust associations between PAH exposure (urinary 1-OHP concentrations), MetS prevalence, and cardiovascular risk (AIP). The real significance of the findings in this study needs to be clarified completely, as MetS and cardiovascular diseases represent a critical challenge in contaminated zones of developing countries such as Mexico.

Research on heat-induced food contaminants, such as furan, has shown its harmful effects on various systems. However, the impact of furan on Sertoli cells, a crucial male reproductive system cell, has not been studied. The investigation involved the treatment of furan to TM4 Sertoli cells at various concentrations (750, 1500, and 3000 µM) over a period of 24 h. This in vitro study determined that furan causes a decrease in Sertoli cell viability and an increase in lactate dehydrogenase activity, leading to cytotoxicity. Additionally, we observed an increase in MDA, one of the oxidative stress markers, in Sertoli cells, indicating that furan exposure leads to lipid peroxidation. It was determined that enzyme activities in the antioxidant defense system in Sertoli cells decreased after furan exposure. The findings indicate that furan induces oxidative damage in Sertoli cells by impairing the activity of antioxidant enzymes and promoting the production of ROS. This study discovered that furan triggers apoptosis in Sertoli cells by damaging DNA and altering the expression levels of apoptotic genes. Moreover, results suggest that furan causes cellular toxicity and apoptosis, leading to damage to Sertoli cells and thus causing male infertility.

Mosquitoes serve as vectors for life-threatening parasitic diseases, presenting a continuous threat throughout human history. This has resulted in the extensive utilization of various mosquito repellents, including liquid mosquito repellents (LMRs), roll-ons, and topical creams. While these products demonstrate significant efficacy, the toxicological implications associated with their use are not yet fully understood and continue to be a subject of debate. The analysis conducted using gas chromatography-mass spectrometry (GC-MS) on LMR revealed the presence of 158 distinct compounds, among which were Piperazine 2,5-dimethyl propyl and a range of hydrocarbons. The analysis of network toxicology indicated that 78 of the examined compounds contravened Lipinski's rule of five and exhibited considerable overlap with target genes associated with lung cancer pathways, thereby highlighting potential concerns regarding their carcinogenic properties. The exposure of zebrafish embryos to LMR concentrations between 0.1 and 14 µg/mL resulted in developmental toxicity assays that demonstrated a dose-dependent escalation in mortality rates and the occurrence of morphological abnormalities, such as pericardial edema and skeletal deformities. Behavioral assays demonstrated a marked decrease in locomotor activity at elevated LMR concentrations, indicating potential neurotoxic effects. Biochemical analyses revealed elevated levels of reactive oxygen species (ROS), enhanced lipid peroxidation, and diminished glutathione, which are indicative of oxidative stress. Enzyme activity assays indicated a reduction in superoxide dismutase (SOD) and catalase (CAT) activities, alongside an increase in lactate dehydrogenase (LDH) activity, which suggests the occurrence of cellular damage. Analysis of gene expression demonstrated significant dysregulation in genes associated with oxidative stress (SOD1, CAT), inflammatory markers (TNF-α, IL-1β), apoptotic regulators (p53, bcl2), and neurobiological genes (brain-derived neurotrophic factor, bdnf). The results highlight the possible health hazards linked to LMR exposure, which manifest as developmental, biochemical, and genetic alterations in zebrafish embryos.

Microplastics (MPs) and antibiotics are prevalent contaminants in terrestrial environment. MPs possess the ability to absorb antibiotics, resulting in the formation of complex pollutants. While the accumulation and fate of MPs and antibiotics in marine ecosystems have been extensively studied, their combined pollution behavior in terrestrial environments remains relatively underexplored. This paper describes the sources, migration, and compound pollution of MPs and antibiotics in soil. It reviews the mechanisms of compound toxicity associated with antibiotics and MPs, combining different biological classifications. Moreover, we highlight the factors that influence the effects of MPs as vectors and the critical elements driving the spread of antibiotic resistance genes (ARGs). These information suggests the potential mitigation measures for MPs contamination from different perspectives to reduce the impact of ARGs-carrying MPs on human health, specifically through transmission via plants, microbes, or terrestrial vertebrates. Finally, we identify gaps in scientific knowledge regarding the interaction between MPs and antibiotics in soil environments, including the need for standardized research methods, multi-dimensional studies on complex ecological effects, and more comprehensive risk assessments of other pollutants on human health. In summary, this paper provides foundational information for assessing their combined toxicity, offers insights into the distribution of these emerging pollutants in soil, and contributes to a better understanding of the environmental impact of these contaminants.

Rhizoma Dioscoreae Bulbiferae (HYZ) is a widely utilized herb in clinical practice, known for its significant biological activities. However, the associated hepatotoxicity poses limitations to its application. Our previous research indicated that the effective mitigation of HYZ-induced hepatotoxicity through the concoction with Radix Paeoniae Alba medicinal juice involves the incorporation of paeoniflorin (Pae) and a reduction in diosbulbin B (DB), the primary toxic compound in HYZ. This finding suggests that the introduced Pae may exert a direct attenuating effect on DB. In light of this, this study represents the first investigation into Pae's detoxification effect against DB-induced hepatotoxicity after administration for 2 months in mice vivo while also exploring underlying mechanisms related to inflammation and ferroptosis based on network pharmacology results. Our findings demonstrate that Pae significantly alleviates DB-induced hepatotoxicity in a dose-dependent manner. Western blotting and ELISA analyses revealed that Pae effectively reversed elevated levels of hepatic inflammation-related markers-such as NF-κB, p38 MAPK, NLRP3, TNF-α, and IL-1β-as well as excessively high concentrations of ferroptosis-related MDA and Fe²⁺. Furthermore, it restored low levels of GSH, SOD, GPX4, and FTH1. In summary, introduced Pae substantially mitigated DB-induced hepatotoxicity by inhibiting both hepatocyte inflammation and ferroptosis.

Bisphenol-A (BPA) is categorized as a major endocrine-disrupting chemical (EDC) used to manufacture many plastic products. BPA affects reproductive performance and promotes infertility by causing hormonal imbalance, mitochondrial dysfunction, and altered gene expression. The present investigation aimed to evaluate the effects of BPA exposure for 28 days on the activity or level of antioxidant response elements (AREs), mRNA expressions of antioxidant genes, and histomorphological changes in the ovary of adult zebrafish. The adult female zebrafish were randomly divided into four experimental groups, viz. control, vehicle (0.01% ethanol), low dose (BPA: 350 µg/L), and high dose (BPA: 700 µg/L) exposure groups. After BPA exposure in both groups, superoxide dismutase (SOD) activity and total antioxidant capacity (TAC) level were significantly (p < 0.05) decreased in the zebrafish ovary. Whereas, catalase (CAT) activity and malondialdehyde (MDA) level were significantly (p < 0.05) increased in both treatment groups. The sod mRNA expression was significantly (p < 0.05) down-regulated in the high-dose BPA-exposed group. Whereas, cat and nuclear factor erythroid 2-related factor 2 (nrf₂) mRNA expressions were significantly (p < 0.05) up-regulated in both BPA-treated groups. Noticeable histomorphological alterations were recorded in the ovary of zebrafish exposed to low and high doses of BPA. The alterations in the activity of ARE, mRNA expressions of antioxidant genes, and histopathological changes suggest that exposure to BPA can cause endocrine disruption and damage to the ovary of adult zebrafish caused by oxidative stress.

The use of agrochemicals as plant growth regulators, pesticides, and soil fertilizers can result in insults among farmers and other non-targeted organisms. The adverse effects of agrochemicals are of global concern, though limited studies have delineated their toxicity on blood cells and inflammatory parameters in Fako division in Cameroon. This study examined the impact of occupational exposure on haematological and inflammatory parameters among farmers in Fako division. Briefly, 165 farmers who occupationally applied agrochemicals and a reference population of 75 non-farmers were interviewed on types of agrochemicals used, knowledge and safety during use of agrochemicals, as well as related symptoms of exposure. Serum cholinesterase (acetylcholinesterase and butyrylcholinesterase) activities were measured as biomarkers of exposure to agrochemicals. Complete blood count and serum levels of interleukin-6 (IL-6) and nitric oxide (NO) were determined as haematological and inflammatory biomarkers. Results disclosed frequent use of insecticides, fungicides, herbicides and fertilizers with neglect of personal protective equipment. Reported symptoms of exposure to agrochemicals were consistent with decrease in cholinesterase activities. Exposure to agrochemicals decreased erythrocyte count and red cell distribution width, as well as increased mean cell volume, mean corpuscular hemoglobin, serum levels of NO and IL-6 in farmers; suggesting anemia and increased cellular inflammation. In conclusion, the use of agrochemicals resulted in inhibited cholinesterase activities, induced anemia, and promoted cell inflammation in farmers. These findings call for more sensitization and training of the farmers to minimize agrochemical exposure and related health hazards.

The absorption of nicotine from smokeless tobacco products (STPs) in humans is affected by various factors, including nicotine content, flavoring compounds, cutting format, tobacco cut sizes, and pH. In this study, participants were asked to use STP 1 for a specific period, after which the nicotine content was measured before and after use to determine the release rate using the Weibull model. Blood samples were collected from participants after 30 min of using STP 1 to assess nicotine pharmacokinetics. Additionally, guinea pigs were administered four types of STPs with varying pH levels, and tobacco cut sizes, but with identical nicotine content on the oral mucosa to evaluate nicotine pharmacokinetics. The human results showed that nicotine in STP was quickly released in the mouth, reaching 73.66% within 30 min. Plasma nicotine concentration in guinea pigs and human participants were comparable following STP use. Guinea pigs exposed to STPs with smaller tobacco cut sizes or higher pH absorbed more nicotine and metabolized it more slowly. The findings suggest that pH and cut size of STPs are key factors affecting nicotine absorption, while the impact of flavoring agents and other components on nicotine absorption remains to be determined.