Thomsenhjort6480

Protein expression level of p38 MAPK and Wnt/β-catenin were significantly increased. UPLC-Q-TOF/MS-based serum metabolomics coupled with pattern recognition methods and pathway analysis provide a powerful approach to identify potential biomarkers and is a new strategy to predict the underlying mechanism of disease caused by environmental toxicant.Boiling water before drinking or using it for cooking is a general practice especially in areas where portable water is not readily available. However, boiling water in an aluminum pot could be a route of entry of heavy metals into humans. This study assessed the genotoxic and mutagenic potential of boiled water samples from aluminum pots of different duration of use using the SOS chromotest on Escherichia coli PQ37 and the Ames fluctuation test on Salmonella typhimurium strains TA98 and TA100, respectively. Three aluminum pots from the same manufacturer but of different years of use (6-year-old, 3-year-old, and new aluminum pots) were used for the experiment. Cariprazine in vitro Six selected heavy metals (Cadmium, Copper, Arsenic, Nickel, Lead, and Aluminum) were also analyzed in the samples using an Atomic Absorption Spectrophotometer (AAS Buck, Scientific model 210 VGP). Cadmium, Copper, Arsenic, Nickel, Lead, and Aluminum were present in all the test water samples at concentrations that were higher than the maximum limit allowable by standard regulatory organizations. link2 The concentrations of these metals in the samples also increased as the duration of use of the aluminum pots increased. The results further showed that the water boiled in the three aluminum pots is mutagenic and genotoxic in both Ames fluctuation and SOS chromotests. The 6-year-old aluminum pot induced the highest mutagenicity and genotoxicity followed by the 3-year-old aluminum pot. The metals in the tested samples were believed to be responsible for the observed mutagenicity and genotoxicity in the microbial assays. The findings of this study revealed that cooking with Aluminum pots could lead to the leaching of heavy metals into food, and pose mutagenic and genotoxic risks to consumers.Alcoholism has been linked to problems with male reproductive function. The combined effects of alcohol, cannabis, and tobacco were compared in this study. A total of 35 rats were assigned randomly into seven groups A-G animals in A were administered distilled water. Animals in B-G were either administered alcohol orally (30 ml 40% alcohol) or exposed to smoke from ignited tobacco (exposure to smoke from 0.7 g tobacco for 5 min) or cannabis (exposure to smoke from 0.7 g tobacco and cannabis for 5 min) B (orally administered alcohol), C (exposed to the smoke from tobacco), D (exposed to smoke from cannabis), E (treated with alcohol and exposed to smoke from tobacco), F (treated with alcohol and exposed to smoke from cannabis), G (treated with alcohol and exposed to smokes from tobacco and cannabis). Assays were carried on the testicular homogenate after a 14-day treatment. There was a significant increase in activity of alkaline phosphatase (P ≤ 0.05), concentrations of cholesterol, glutathione reductase, and malondialdehyde in treated rats by the co-administration of alcohol with cannabis and tobacco compared with the control group. The combined treatment also caused degeneration and morphological distortions of testicular cells. The biochemical and histoarchitectural change was due to oxidative damage attributable to the synergistic effects. The high binding energy of tetrahydrocannabinol ligand to prostate acid phosphatase may be a prediction that the ligand can have an inhibitory effect on the function of enzymes in the prostate.

This study was designed to investigate the effects of liquefied petroleum gas (LPG) on hematotoxic, cardiotoxic, and hepatotoxic indices and the modifying influence of selected polyphenols.

Adult male Wistar rats were exposed to1000ppm LPG for 10min at 12-h interval for 30days with or without cotreatment with 50mg/kg rutin, quercetin, tannic acid, or gallic acid followed by hematological, biochemical, and histopathological evaluations in animal tissues.

Exposure to LPG induced hematotoxicity, cardiotoxicity, and hepatotoxicity. This is reflected in alterations to levels or activities of blood parameters (hemoglobin, packed cell volume, red blood cells, mean corpuscular volume, mean corpuscular hemoglobin, and platelets), enzymatic and nonenzymatic oxidative stress markers, nitrite, lactate dehydrogenase, creatine kinase-MB, transaminases, γ-glutamyl transpeptidase, bilirubin, and plasma albumin. LPG exposure also caused dyslipidemia and histoarchitectural changes. Treatment with the selected polyphenols effectively attenuated LPG-induced toxicity in rat tissues.

The results indicate that continuous exposure to LPG could lead to blood-, heart-, and liver-related diseases and dietary polyphenols could provide benefits in diseases associated with LPG inhalation toxicity.

The results indicate that continuous exposure to LPG could lead to blood-, heart-, and liver-related diseases and dietary polyphenols could provide benefits in diseases associated with LPG inhalation toxicity.Cypermethrin, one kind of pyrethroid pesticides, has been shown to act as endocrine-disrupting chemicals (EDCs). The purpose of this study was to explore the roles of Sertoli cell apoptosis through mitochondrial pathway associated with calcium (Ca2+) in cypermethrin-induced male reproductive toxicology. The mouse Sertoli cells TM4 were cultured with 0 μM, 10 μM, 20 μM, 40 μM and 80 μM of cypermethrin. We used flow cytometry, Fluo-4 AM, western blot and JC-1 Assay Kit to examine apoptosis, intracellular Ca2+, expressions of mitochondrial apoptotic pathway-related proteins and mitochondrial membrane potential. We found cypermethrin increased apoptosis rate of TM4 cells significantly and with a significant increase in intracellular Ca2+ concentration. Cypermethrin significantly decreased the protein expressions of cytosolic B-cell lymphoma-2 (Bcl-2) and mitochondrial cytochrome c (Cyt-c). The protein expressions of cytosolic Bcl-2-associated x (Bax), Cyt-c, cleaved caspase-3, calmodulin (CaM), Ca2+/CaM-dependent protein kinases II (CaMKII) and phosphorylated CaMKII were increased significantly in cypermethrin-exposed TM4 cells. Cypermethrin decreased mitochondrial membrane potential significantly. Then, Bcl-2 family and Ca2+/CaM/CaMKII pathway participate in cypermethrin-induced homeostasis. Ca2+ overload activates mitochondrial pathway by increasing permeability of mitochondrial membrane and decreasing mitochondrial membrane potential. We suggest cypermethrin induces Sertoli cell apoptosis involving mitochondrial pathway associated with Ca2+ regulated by Bcl-2 family and Ca2+/CaM/CaMKII pathway. The study provides a new insight into mechanisms involved in cypermethrin-induced male reproductive toxicology.Paraquat (PQ) and diquat (DQ), two highly efficient herbicides sharing similar chemical backbone, both induce reactive oxygen species and are highly toxic to humans and livestock, however, PQ but not DQ poisoning result in pulmonary fibrosis, the leading cause of high mortality rate in patients suffering PQ toxicity. Understanding the unique mechanism of PQ different from DQ therefore would provide potential strategies to reduce PQ-induced pulmonary fibrosis. Here, we identified that PQ but not DQ continuously upregulates TGF-β expression in alveolar type II (AT II) cells. Importantly, such high expression of TGF-β increases cytosolic calcium levels and further promotes the activation of calcineurin-NFAT axis. TGF-β mainly activates NFATc1 and NFATc2, but not NFATc3 or NFATc4. Administration of the inhibitors targeting cytosolic calcium or calcineurin largely reverses PQ-induced epithelial-mesenchymal transition (EMT), whereas DQ has little effects on activation of NFAT and EMT. Ultimately, PQ poisoned patients exhibit significantly reduced blood calcium levels compared to DQ poisoning, possibly via the large usage of calcium by AT II cells. All in all, we found a vicious cycle that the upregulated TGF-β in PQ-induced EMT further aggravates EMT via promotion of the calcium-calcineurin axis, which could be potential drug targets for treating PQ-induced pulmonary fibrosis.Alternariol (AOH), a mycotoxin belonging to the genus Alternaria, has been shown to induce cytotoxicity, including apoptosis and cell cycle arrest, in several mammalian cell types. However, its effects on early-stage embryonic development require further investigation. Here, we have shown that AOH exerts embryotoxic effects on mouse blastocyst-stage embryos and long-term adverse effects on immunity in one-day-old newborn mice of the next generation. Significant apoptosis and decrease in total cell number, predominantly through loss of inner cell mass (ICM), and to a minor extent, trophectoderm (TE) cells, were observed in AOH-treated blastocysts. Moreover, AOH exerted detrimental effects on pre- and post-implantation embryo development potential and induced a decrease in fetal weight in in vitro development and embryo transfer assays. Injection of pregnant mice with AOH (1, 3 and 5 mg/kg body weight/day) for 4 days resulted in apoptosis of blastocyst-stage embryos and injurious effects on embryonic development from the zygote to blastocyst stage or embryo degradation and a further decrease in fetal weight. Furthermore, AOH exerted a long-term impact on the next generation, triggering a significant increase in total oxidative stress content and expression of genes encoding antioxidant proteins. Lower expression of CXCL1, IL-1β and IL-8 related to innate immunity was detected in liver tissue extracts obtained from one-day-old newborns of AOH-injected pregnant mice (5 mg/kg body weight/day) relative to their non-treated counterparts. In addition, ROS served as an upstream regulator of AOH-triggered apoptotic processes and impairment of embryonic development. Our collective results highlight the potential of AOH as an embryotoxic and immunotoxic risk factor during embryo and infant development stages in mice.Benzene, a known occupational and environmental contaminant, has been recognized as the hematotoxin and human carcinogen. Lipids have a variety of important physiological functions and the abnormal lipid metabolism has been reported to be closely related to the occurrence and development of many diseases. In the present study, we aim to utilize LC-MS/MS lipidomic platform to identify novel biomarkers and provide scientific clues for mechanism study of benzene hematotoxicity. Results showed that a total of 294 differential metabolites were obtained from the comparison of benzene-treated group and control group. The glycerophospholipid pathway was altered involving the down-regulation of the levels of phosphatidylcholine and phosphatidylserine. link3 In addition, phosphatidylethanolamine (PE) and 1-Acyl-sn-glycero-3-phosphocholine levels were increased in benzene-treated group. Based on the relationship between PE and autophagy, we then found that effective biomarker of autophagy, Beclin1 and LC3B, were increased remarkably. Furthermore, following benzene treatment, significant decreases in glucosylceramide (GlcCer) and phytosphingosine (PHS) levels in sphingolipid pathway were observed. Simultaneously, the levels of proliferation marker (PCNA and Ki67) and apoptosis regulator (Bax and Caspase-3) showed clear increases in benzene-exposed group. Based on our results, we speculate that disturbances in glycerophospholipid pathway play an important role in the process of benzene-induced hematopoietic toxicity by affecting autophagy, while sphingolipid pathway may also serve as a vital role in benzene-caused toxicity by regulating proliferation and apoptosis. Our study provides basic study information for the future biomarker and mechanism research underlying the development of benzene-induced blood toxicity.