Toxicology Mechanisms and Methods

Fine particulate matter (PM2.5 ) increases the risks of lung cancer. Epigenetics provides a new toxicology mechanism for the adverse health effects of PM2.5 . However, the regulating mechanisms of PM2.5 exposure on candidate gene DNA methylation changes in the development of lung cancer remain unclear. Abnormal expression of the glutathione S transferase (GST) gene is associated with cancer. However, the relationship between PM2.5 and DNA methylation-mediated GST gene expression is not well understood. In this study, we performed GST DNA methylation analysis and GST-related gene expression in human A549 cells exposed to PM2...

Toxicity profiling is an integral part of the drug discovery pipeline. The 3Rs principle - Replacement, Reduction, and Refinement, is considered a golden rule in determining the most appropriate approach for toxicity studies. The acute toxicity study with proper estimate of median lethal dose (LD50 ) is usually an initial procedure for the determination of most suitable test doses for preclinical toxicological and pharmacological profiling. Several methods, that have been devised to determine the LD50 , are faced with the challenge of using a large number of animals and time constraints...

The new technological applications of nickel (Ni) raise concerns over its harmful effects on the environment and human health. Pomiferin isolated from Osage orange is evaluated in in vitro and in vivo laboratory bioassays. This study focused the effects of pomiferin on Ni-caused hepatic injury and its underlying mechanisms. With this aim, Sprague-Dawley rats received 10 mg/kg nickel chloride (NiCl2 ) for 7 d by intraperitoneal injections. Pomiferin was given orally once a day at different doses (75, 150, and 300 mg/kg) for 20 d after exposure to NiCl2 ...

This study aimed to examine the expression and biological functions of ACTL6A in glioma cells (U251), the effects of sulforaphane on the growth of U251 cells and the involvement of the ACTL6A/PGK1 pathway in those effects. The U251 cell line was transfected with ACTL6A over-expression plasmids to upregulate the protein, or with ACTL6A inhibitor to underexpress it, then treated with different concentrations of sulforaphane. Cell viability, proliferation, and apoptosis were assessed using standard assays, and levels of mRNAs encoding ACTL6A, PGK1, cyclin D1, Myc, Bax or Bcl-2 were measured using quantitative real-time polymerase chain reaction (qRT-PCR)...

Nonalcoholic fatty liver disease (NAFLD) has emerged as a major chronic liver illness characterized by increase of lipid content in the liver. This study investigated the role of lauric acid to treat NAFLD in male adult Sprague Dawley rats. In this study, to induce NAFLD in the rats, a high-fat diet (HFD) was administered for eight consecutive weeks. Lauric acid groups received lauric acid (250 and 500 mg/kg; orally), concurrently with HFD for eight consecutive weeks. Lauric acid could ameliorate the serum levels of TG, TC, ALT, AST, blood glucose, and insulin...

Per- and Polyfluoroalkyl Substances (PFAS) are synthetic chemicals utilized in the production of various products that possess water and dirt-repellent properties. Exposure to PFAS has been linked to numerous diseases, such as cancer and preeclampsia (PE). However, whether PFAS contributes to the advancement of PE remains uncertain. In this study, we conducted an extensive bioinformatics analysis using the Comparative Toxicogenomics Database (CTD) and Gene Expression Omnibus (GEO) databases, leading us to discover a connection between PE and four specific PFAS...

The current study aimed to assess the antioxidant and antiproliferative effects of teucrium polium extract: computational and in vivo study in rats. Three groups of animals: Group (i) constitute the control group; Group (ii) HeLa group received an intrafemoral inoculation of HeLa cells and Group (iii) constitue the combination between HeLa + T. polium . The plant was administered by gavage. Our results revealed that HeLa cell injection showed an elevation in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TB), creatinine, urea, calcium and phosphorus...

The modulatory role of primrose oil (PO) supplementation enriched with γ-linolenic acid and D/L-alpha tocopherol acetate against a carbon tetrachloride (CCl4 )-induced liver damage model was assessed in this study. Twenty male albino rats were divided into four groups. The control group received corn oil orally. The PO group received 10 mg/kg P O orally. The CCl4 group received 2 mL/kg CCl4 orally and PO/CCl4 group; received PO and 2 mL/kg CCl4 orally. The relative liver weight was recorded...

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Torsional stress in double-stranded DNA enables and regulates facets of chromosomal metabolism, replication and transcription, and requires regulatory enzymatic systems including topoisomerases and histone methyltransferases. As such, this machinery may be subject to deleterious effects from reactive mutagens, including ones from carcinogenic polycyclic aromatic hydrocarbon (PAH) adduct formation with DNA. Supercoiled plasmid DNA was investigated for its torsional responses to adducts formed in vitro from PAH benzylic carbocation reactive intermediates created spontaneously by release of leaving groups...

Gentamicin, an aminoglycoside antibiotic, is nowadays widely used in the treatment of gram-negative microorganisms. The antimicrobial, anti-inflammatory, and antioxidant activities of eucalyptol, a type of saturated monoterpene, have been reported in many studies. The aim of this study was to examine the possible effects of eucalyptol on gentamicin-induced renal toxicity. A total of 32 rats were divided into 4 groups; Control (C), Eucalyptol (EUC), Gentamicin (GEN), and Gentamicin + Eucalyptol (GEN + EUC)...

Side effects of doxorubicin (DOX) are mainly due to oxidative stress, with the involvement of inflammatory and apoptotic mechanisms. Agomelatine (AGO) is a melatonin receptor agonist with antioxidant, anti-inflammatory, and anti-apoptotic features. This study aimed to evaluate the effects of AGO with different doses on DOX-induced neurotoxicity. Rats were divided into four groups as control, DOX (40 mg/kg, intraperitoneal single dose), DOX + AGO20 (20 mg/kg AGO oral gavage for 14 days), and DOX + AGO40 (40 mg/kg AGO oral gavage for 14 days)...

Tremor is one of the effects of nicotine as a toxic substance, especially in animal models. The intensity and duration of tremors were used to evaluate the effect of nicotine on locomotor activity in laboratory animals. In our observations, the time interval between nicotine injection and the onset of tremor changed depending on the dose. Therefore, by increasing the dose of nicotine in rats, the time interval of tremor onset was also shortened. These results suggest that the time interval between nicotine injection and the onset of tremors can be used as a complementary index for better evaluation of nicotine-derived motor disturbances...

Parkinson's disease (PD) is often accompanied by depression, which may appear before motor signs. Oleanolic acid (OA), a pentacyclic triterpenoid substance, have many pharmacological properties. However, its efficacy in treating PD-related chronic unpredictable stress (CUS) is unknown. Our study used behavioral, biochemical, and immunohistochemical techniques to assess how OA affected PDrelated CUS. Rotenone (1 mg/kg i.p. for first 21 days) was used to induce Parkinsonism, and modest psychological & environmental stresses generated CUS (from day 22 to day 43) in animals...

Polymeric poly lactic-co-glycolic acid (PLGA)-lipid hybrid nanoparticles (PNPs)-based therapy are powerful carriers for various therapeutic agents. The present study was conducted to evaluate the chemotherapeutic potential of free 5-flurouracil (5FU) and synthetized 5FU-PNPs and impact on p53-dependent apoptosis in mammary carcinomas grown in mice. Breast cancer cells were injected in Swiss albino female mice and 2 bilateral masses of mammary carcinoma (MC) were confirmed after one week. Mice were distributed to five experimental groups; Group1: MC control group...

Liver diseases preceding the occurrence of hepatocellular carcinoma (HCC) play a crucial role in the progression and establishment of HCC, a malignancy ranked as the third deadliest cancer worldwide. Late diagnosis, alongside ineffective treatment, leads patients to a poor survival rate. This scenario argues for seeking novel alternatives for detecting liver alterations preceding the early occurrence of HCC. Experimental studies have reported that ABCC3 protein increases within HCC tumors but not in adjacent tissue...

Continuous smoking leads to adaptive regulation and physiological changes in lung tissue and cells, and is an inductive factor for many diseases, making smokers face the risk of malignant and non-malignant diseases. The impact research is getting more and more in-depth, but the stimulant effect, mechanism of action and response mechanism of the main cells in the lungs caused by smoke components have not yet been fully elucidated, and the early diagnosis and identification of various diseases induced by smoke toxins have not yet formed a systematic relationship method...

PURPOSE: This study sought to identify drug target genes and their associated molecular mechanisms during isoflurane-induced anesthesia in clinical applications. METHODS: Microarray data (ID: GSE64617; isoflurane-treated vs. normal samples) were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened and hub genes were investigated using weighted correlation network analysis (WGCNA). Protein-protein interactions (PPIs) were constructed among the co-DEGs (common genes between DEGs and hub genes), followed by functional enrichment analyses...

The Threshold of Toxicological Concern (TTC) is an approach for assessing the safety of chemicals with low levels of exposure for which limited toxicology data are available. The original TTC criteria were derived for oral exposures from a distributional analysis of a dataset of 613 chemicals that identified 5th percentile no observed effect level (NOEL) values grouped within three tiers of compounds having specific structural functional groups and/or toxic potencies known as Cramer I, II and III classifications...

This study aimed to understand the gender-specific alcohol-induced biochemical changes and TBARS association with the endocrine system. Human male and female subjects ranging from 35 ± 10 years old with an 8-10-year drinking history were included in the study. The results demonstrated that testosterone levels were lower in male alcoholics and higher in female alcoholics, as well as higher estrogen and cortisol levels in both genders. In addition, we found lower T3, T4, and thyroid-stimulating hormone (TSH) levels in alcoholics of both sexes...