 Subjects -> PHARMACY AND PHARMACOLOGY (Total: 575 journals)
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- Association between urinary arsenic concentration and genetic
polymorphisms in Korean adults-
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Abstract: Abstract Arsenic (As) is a human carcinogen widely distributed in the environment. This study evaluated the association between the urinary As concentration and single nucleotide polymorphisms (SNPs) in Korean adults to determine the genetic factors related to As concentration. The study included 496 participants for the genome-wide association study (GWAS) and 1483 participants for the candidate gene approach study. Participants were 19 years and older. The concentrations of total As (Tot As) and total As metabolites (Tmet As, the sum of inorganic As and their metabolites; arsenite, arsenate, monomethylarsonic, and dimethylarsinic acid) in the urine were analyzed. The GWAS identified four SNPs (rs1432523, rs3776006, rs11171747, and rs807573) associated with urinary Tot As and four SNPs (rs117605537, rs3776006, rs11171747, and rs148103384) significantly associated with urinary Tmet As concentration (P < 1 × 10–4). The candidate gene study identified two SNPs (PRDX2 rs10427027 and GLRX rs3822751) in genes related to the reduction reaction associated with urinary Tot As and Tmet As. This study suggests that genetic factors may play a role in regulating As metabolism in the human body, affecting both exposure levels and its potential health risks in the general Korean population, even at low exposure levels.
PubDate: 2023-11-23
- Distribution of molybdenum in soft tissues and blood of rats after
intratracheal instillation of molybdenum(IV) sulfide nano- and
microparticles-
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Abstract: Abstract There is still little literature data on the toxicity and safety of the commonly used molybdenum (Mo) disulfide which is present in the working as well as living environments. Thus, an experiment was carried out involving rats, with single and repeated intratracheal exposure (in the latter case, 7 administrations at 2-week intervals with the analysis performed after 90 days) to lower (1.5 mg Mo kg−1 b.w.) and higher (5 mg Mo kg−1 b.w.) doses of molybdenum(IV) sulfide nanoparticles (MoS2-NPs) and microparticles (MoS2-MPs). The analysis of Mo concentrations in the tail and heart blood as well as in soft tissues (lung, liver, spleen, brain), after mineralization and bioimaging, was meant to facilitate an assessment of its accumulation and potential effects on the body following short- and long-term exposure. The multi-compartment model with an exponential curve of Mo concentration over time with different half-lives for the distribution and elimination phases of MoS2-MPs and MoS2-NPs was observed. After 24 h of exposure, a slight increase in Mo concentration in blood was observed. Next, Mo concentration indicated a decrease in blood concentration from 24 h to day 14 (the Mo concentration before the second administration), below the pre-exposure concentration. The next phase was linear, less abrupt and practically flat, but with an increasing trend towards the end of the experiment. Significantly higher Mo concentrations in MoS2-NPs and MoS2-MPs was found in the lungs of repeatedly exposed rats compared to those exposed to a single dose. The analysis of Mo content in the liver and the spleen tissue showed a slightly higher concentration for MoS2-NPs compared to MoS2-MPs. The results for the brain were below the calculated detection limit. Results were consistent with results obtained by bioimaging technique.
PubDate: 2023-11-14
- Comparative study on estrogen receptor alpha dimerization and
transcriptional activity of parabens-
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Abstract: Abstract Parabens are used as preservatives in various household products, including oral products, cosmetics, and hair/body washes. In recent years, the widespread use of parabens has raised concerns due to the potential health risks associated with their estrogenic effects. In the present study, we evaluated and compared the estrogenic activity of parabens using two cell-based in vitro tests: (1) bioluminescence resonance energy transfer (BRET)-based estrogen receptor alpha (ERα) dimerization using HEK293 cells that were stably transfected with ERα‐fused NanoLuc luciferase (Nluc) and HaloTag (HT) expression vector, and (2) stably transfected transcriptional activation (STTA) assays using ERα-HeLa9903 cells. The following parabens were tested using the BRET‐based ERα dimerization assay and showed estrogenic activity (PC20 values): methyl paraben (MP, 5.98 × 10−5 M), ethyl paraben (EP, 3.29 × 10−5 M), propylparaben (PP, 3.09 × 10−5 M), butyl paraben (BP, 2.58 × 10−5 M), isopropyl paraben (IsoPP, 1.37 × 10−5 M), and isobutyl paraben (IsoBP, 1.43 × 10−5 M). Except MP, all other parabens tested using the STTA assay also showed estrogenic activity: EP, 7.57 × 10−6 M; PP, 1.18 × 10−6 M; BP, 3.02 × 10−7 M; IsoPP, 3.58 × 10−7 M; and IsoBP, 1.80 × 10−7 M. Overall, EP, PP, BP, IsoPP, and IsoBP tested positive for estrogenic activity using both assays. These findings demonstrate that most parabens, albeit not all, induce ERα dimerization and possess estrogenic activity.
PubDate: 2023-10-05
- Molecular mechanism of empagliflozin cardioprotection in 5-fluorouracil
(5-FU)-induced cardiotoxicity via modulation of SGLT2 and TNFα/TLR/NF-κB
signaling pathway in rats-
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Abstract: Abstract One of the commoly used chemotherapeutic agents is 5-Fluorouracil (5-FU). Unfortunately, the clinical administration of 5-FU is complicated with serious cardiotoxic effects and the safe use becomes an urgent task in cardio-oncology. Till now, there are no studies discussed the role of empagliflozin (EMP) against 5-FU cardiotoxicity. Thus, we investigated this effect and the involved mechanisms in 5-FU induced heart injury. Forty male rats of Wistar albino species were used and divided randomly into four groups. Group I is the control group, group II is EMP given group, group III is 5-FU cardiotoxic group and group IV is 5-FU plus EMP group. 5-FU (150 mg/kg) was administered as a single intraperitoneal (i.p.) dose on 1st day to induce cardiotoxicity with or without EMP (30 mg/kg/d) orally for 5 days. The dose of 5-FU is relevant to the human toxic dose. Our data showed that 5-FU given group caused cardiotoxicity with significant increase of serum cardiac enzymes, toll like receptors, enhancement of nuclear factor kappa B (NF-κB), interleukin1β (IL1β), IL6, myeloid-differentiation-factor 88 (MYD88), heart weight, malondialdehyde (MDA), tumor-necrosis-factor-alpha (TNFα), sodium glucose co-transporter 2 (SGLT2), P53 and caspase3 expression with clear histopathological features of cardiotoxicity. Moreover, there is a significant decrease in reduced glutathione (GSH) and total antioxidant capacity (TAC). Interestingly, co-administration of EMP could ameliorate 5-FU induced biochemical and histopathological changes. This effect may be due to modulation of SGLT2, decreasing inflammation, oxidative stress and apoptosis with downregulation of an essential inflammatory cascade that mediates 5-FU cardiotoxicity; TNFα/TLR/NF-κB.
PubDate: 2023-10-03
- Characterisation of changes in global genes expression in the lung of ICR
mice in response to the inflammation and fibrosis induced by polystyrene
nanoplastics inhalation-
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Abstract: Abstract This study characterised the changes in global gene expression in the lung of ICR mice in response to the inflammation and fibrosis induced by the inhalation of 0.5 μm polystyrene (PS)-nanoplastics (NPs) at various concentrations (4, 8, and 16 μg/mL) for 2 weeks. The total RNA extracted from the lung tissue of NPs-inhaled mice was hybridised into oligonucleotide microarrays. Significant upregulation was detected in several inflammatory responses, including the number of immune cells in bronchoalveolar lavage fluid (BALF), the expression level of inflammatory cytokines, mucin secretion, and histopathological changes, while they accumulated average of 13.38 ± 1.0 μg/g in the lungs of the inhaled ICR mice. Similar responses were observed regarding the levels of fibrosis-related factors in the NPs-inhaled lung of ICR mice, such as pulmonary parenchymal area, expression of pro-fibrotic marker genes, and TGF-β1 downstream signalling without any significant hepatotoxicity and nephrotoxicity. In microarray analyses, 60 genes were upregulated, and 55 genes were downregulated in the lung of ICR mice during inflammation and fibrosis induced by NPs inhalation compared to the Vehicle-inhaled mice. Among these genes, many were categorised into several ontology categories, including the anatomical structure, binding, membrane, and metabolic process. Furthermore, the major genes in the upregulated categories included Igkv14-126000, Egr1, Scel, Lamb3, and Upk3b. In contrast, the major genes in the down-regulated categories were Olfr417, Olfr519, Rps16, Rap2b, and Vmn1r193. These results suggest several gene functional groups and individual genes as specific biomarkers respond to inflammation and fibrosis induced by PS-NPs inhalation in ICR mice.
PubDate: 2023-10-01
- Endotoxin of Porphyromonas gingivalis amplifies the inflammatory response
in hyperglycemia-induced zebrafish through a mechanism involving
chitinase-like protein YKL-40 analogs-
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Abstract: Abstract Porphyromonas gingivalis (P. gingivalis), a key pathogen in periodontal diseases, is also associated with hyperglycemia-associated systemic diseases, including diabetes mellitus (DM). Gingipains are the most important endotoxins of P. gingivalis, and in vivo studies using gingipains are scarce. Zebrafish (Danio rerio) is a vertebrate with high physiological and genetic homology with humans that has multiple co-orthologs for human genes, including inflammation-related proteins. The aim of our study was to determine the effects of gingipain in a hyperglycemia-induced zebrafish model by evaluating inflammation, oxidant-antioxidant status, and the cholinergic system. Adult zebrafish were grouped into the control group (C), hyperglycemia-induced group subjected to 15 days of overfeeding (OF), gingipain-injected group (GP), and gingipain-injected hyperglycemic group (OF + GP). At the end of 15 days, an oral glucose tolerance test (OGTT) was performed, and fasting blood glucose (FBG) levels were measured. Lipid peroxidation (LPO), nitric oxide (NO), glutathione (GSH), glutathione S-transferase, catalase, acetylcholinesterase (AChE), alkaline phosphatase (ALP), and sialic acid (SA) levels were determined spectrophotometrically in the hepatopancreas. The expression levels of tnf-⍺, il-1β, ins, crp, and the acute phase protein YKL-40 analogs chia.5 and chia.6 were evaluated by RT‒PCR. After two weeks of overfeeding, significantly increased weight gain, FBG, and OGTT confirmed that the zebrafish were hyperglycemic. Increased oxidative stress, inflammation, and AChE and ALP activities were observed in both the overfeeding and GP groups. Amplification of inflammation and oxidative stress was evident in the OF + GP group through increased expression of crp, il-1β, chia.5, and chia.6 and increased LPO and NO levels. Our results support the role of gingipains in the increased inflammatory response in hyperglycemia-associated diseases.
PubDate: 2023-10-01
- AXL is required for hypoxia-mediated hypoxia-inducible factor-1 alpha
function in glioblastoma-
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Abstract: Abstract Glioblastoma (GBM) is the most aggressive type of central nervous system tumor. Molecular targeting may be important when developing efficient GBM treatment strategies. Sequencing of GBMs revealed that the receptor tyrosine kinase (RTK)/RAS/phosphatidylinositol-3-kinase pathway was altered in 88% of samples. Interestingly, AXL, a member of RTK, was proposed as a promising target in glioma therapy. However, the molecular mechanism of AXL modulation of GBM genesis and proliferation is still unclear. In this study, we investigated the expression and localization of hypoxia-inducible factor-1 alpha (HIF-1α) by AXL in GBM. Both AXL mRNA and protein are overexpressed in GBM. Short-interfering RNA knockdown of AXL in U251-MG cells reduced viability and migration. However, serum withdrawal reduced AXL expression, abolishing the effect on viability. AXL is also involved in hypoxia regulation. In hypoxic conditions, the reduction of AXL decreased the level and nuclear localization of HIF-1α. The co-expression of HIF-1α and AXL was found in human GBM samples but not normal tissue. This finding suggests a mechanism for GBM proliferation and indicates that targeting AXL may be a potential GBM therapeutic.
PubDate: 2023-10-01
- Pelargonium sidoides extract mediates nephrotoxicity through mitochondrial
malfunction and cytoskeleton destabilization-
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Abstract: Abstract We investigated the cytotoxic effect of Pelargonium sidoides extract on Madin–Darby canine kidney (MDCK) cells. P. sidoides extract decreased the cell viability in a dose dependent manner (> 0.2%). The extract of P. sidoides decreased the mitochondrial action potential, increased the number of reactive oxygen species (ROS) inside the cell, and caused nicotinamide adenine dinucleotide hydride (NADH) to be released, all of which are signs of mitochondrial dysfunction. The results of unbiased mRNA sequencing showed that 0.3% P. sidoides extract upregulates the apoptosis-related gene (BBC3). This finding was supported by immunoblot analysis of apoptosis signal pathways, which included Bcl-2, Bax, cytochrome C (CytC), cleaved caspase 3 (CC3), cleaved caspase 7 (CC7), cleaved caspase 9 (CC9) and cleaved PARP (CP). It is interesting to note that the elevated levels of Bax, CytC, CC3, CC7, and CC9, as well as CP, were suppressed by N-acetyl-L-cysteine (NAC) pretreatment, which points to ROS-mediated apoptosis. The small GTPases, RhoA, and Rac1/cdc42-GTP-bound active form were all lowered when P. sidoides extract was used. Also, RhoA-related cytoskeleton signals (ROCK, p-LIMK1/2, p-cofilin) and Rac1/cdc42-related signals (N-WASP, WAVE-2) were inhibited by P. sidoides extract. NAC or RhoA/Rac1/cdc42 activator pretreatment reduced P. sidoides extract-induced actin destabilization. In this work, P. sidoides extract promotes apoptosis by causing mitochondrial dysfunction and cytoskeleton disassembly.
PubDate: 2023-10-01
- Integrative roles of sphingosine kinase in liver pathophysiology
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Abstract: Abstract Bioactive sphingolipids and enzymes that metabolize sphingolipid-related substances have been considered as critical messengers in various signaling pathways. One such enzyme is the crucial lipid kinase, sphingosine kinase (SphK), which mediates the conversion of sphingosine to the potent signaling substance, sphingosine-1-phosphate. Several studies have demonstrated that SphK metabolism is strictly regulated to maintain the homeostatic balance of cells. Here, we summarize the role of SphK in the course of liver disease and illustrate its effects on both physiological and pathological conditions of the liver. SphK has been implicated in a variety of liver diseases, such as steatosis, liver fibrosis, hepatocellular carcinoma, and hepatic failure. This study may advance the understanding of the cellular and molecular foundations of liver disease and establish therapeutic approaches via SphK modulation.
PubDate: 2023-10-01
- Protective effects of cardamom aqueous extract against tamoxifen-induced
pancreatic injury in female rats-
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Abstract: Abstract Tamoxifen (TAM) is a commonly used drug for breast cancer treatment. Although effective, TAM has deleterious effects on many organs. The toxic effects of TAM on the pancreas and the underlying mechanisms however, have not fully investigated. In the present study, we investigated the effects of TAM on the pancreatic tissue in female rats. We also examined whether cardamom aqueous extract (CAE) protects against TAM-induced pancreatic injury. TAM-intoxicated rats were injected with 45 mg/kg of TAM for 10 days, whereas rats in the CAE-treated group were administered 10 mL/kg of CAE for 20 days, starting 10 days prior to TAM administration. Treatment with TAM resulted in severe degeneration of the pancreatic acini and marked increases in the serum levels of pancreatic lipase, α-amylase, glucose, fatty acids and triglycerides along with decreased insulin serum levels. TAM led to oxidative stress as evident from a significant increase in the pancreatic levels of lipid peroxides and nitric oxide along with the depletion of reduced glutathione, glutathione peroxidase, and superoxide dismutase. Moreover, inflammation was indicated by a significant increase in tumor necrosis factor–α and interleukin-6 levels, enhanced expression of the macrophage recruitment marker; CD68 as well as up-regulated protein levels of toll-like receptor 4 and nuclear factor kappa B and increased p-p38/MAPK ratio; which are important signals in the production of inflammatory cytokines. TAM also markedly increased the pancreatic levels of caspase-3 and BAX reflecting its apoptotic effects. The CAE treatment ameliorated all the biochemical and histological changes induced by TAM. The present study revealed, for the first time, that TAM has toxic effects on the pancreatic tissue through oxidative stress, inflammation and apoptotic effects. The present study also provides evidence that CAE exerts cytoprotective effects against these deleterious effects induced by TAM in the pancreatic tissue.
PubDate: 2023-10-01
- Carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone-induced toxicities in
rats: comparative study with other mitochondrial uncouplers
(2,4-dinitrophenol, OPC-163493 and tolcapone)-
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Abstract: Abstract FCCP (carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone) is known to inhibit oxidative phosphorylation as a protonophore, dissipating the proton gradient across the inner mitochondrial membrane. To understand the toxicity of FCCP, 3-day, 2- and 4-week repeated oral dose studies were performed in male rats. In the 3-day and 2-week repeated dose toxicity studies, observations included salivation, increased body temperature, and dead and moribund animals. Increased liver weight was observed in conjunction with hydropic degeneration and centrilobular necrosis of hepatocytes. In addition, pathological changes were observed in the pancreas, testis, epididymal duct, stomach and parotid gland. Electron microscopic examination revealed mitochondrial pleomorphism in the hepatocytes. Swelling of mitochondria was observed in the alpha cells and beta cells of the pancreas. Dilatation of rough endoplasmic reticulum, Golgi bodies and loss of secretory granules were also noted in the beta cells of the pancreas. FCCP was also compared with three other mUncouplers (DNP, OPC-163493 and tolcapone) with regard to in vitro mitochondrial uncoupling (mUncoupling) activities. FCCP produced the peak ΔOCR (oxygen consumption rate) at the lowest concentration (0.4 μM), followed by OPC-163493, tolcapone, and DNP, based on peak values in ascending order of concentration (2.5, 10, and 50 μM, respectively). Considering the relationship between the mUncoupling activity and toxicity profile of the four mUncouplers, there is no parallel relationship between the in vitro mUncoupling activity and the degree of in vivo toxicity. These findings may contribute to the efficient development of new mitochondrial uncoupler candidates.
PubDate: 2023-10-01
- Atg5 knockout induces alternative autophagy via the downregulation of Akt
expression-
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Abstract: Abstract Autophagy play contradictory roles in cellular transformation. We previously found that the knockout (KO) of autophagy-related 5 (Atg5), which is essential for autophagy, leads to the malignant transformation of NIH 3T3 cells. In this study, we explored the mechanism by which autophagy contributes to this malignant transformation using two transformed cell lines, Atg5 KO and Ras-NIH 3T3. Monomeric red fluorescent protein–green fluorescent protein–light chain 3 reporter and Cyto-ID staining revealed that Ras-NIH 3T3 cells exhibited higher basal autophagy activity than NIH 3T3 cells. Additionally, transformed cells, regardless of their Atg5 KO status, were more sensitive to autophagy inhibitors (SBI-0206965, chloroquine, and obatoclax) than the untransformed NIH 3T3 cells, suggesting that the transformed cells are more autophagy-dependent than the normal cells. Loss of Atg5 improved the cell viability and mobility, especially in Ras-NIH 3T3 cells. Furthermore, we discovered that autophagy was alternatively induced in a Rab9-dependent manner in Ras-NIH 3T3 and NIH 3T3/Atg5 KO cells. In particular, Atg5 KO cells showed reduced mTOR-mediated phosphorylation of Akt (pAkt S473), indicating the mTOR-independent occurrence of alternative autophagy in Atg5 KO cells. Therefore, our study provides evidence that alternative autophagy may contribute to tumorigenesis in cells with an impaired Atg5-dependent autophagy pathway.
PubDate: 2023-10-01
- A regional approach for health risk assessment of toxicants in plastic
food containers-
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Abstract: Abstract Plastic food containers are being used popularly, generating a waste of about 115 million tons in Vietnam. Such waste is causing environmental and health issues. This study conducted a field survey with 250 local people and selected 59 samples out of 135 plastic food containers collected in Go Vap district, Vietnam. Collected plastic samples identified compositions were PET 13.6%, PP 28.8%, PS 16.9%, and 40.7% undefined plastics. Collected plastic samples were classified based on the plastic type using recycling code and quantitatively analyzed with X-ray fluorescence spectroscopy method to assess concentrations of Cd, Sb, Pb, Hg, Sn, Cr, Br, Cl, and S. Most of these collected plastic samples (91.5%) were found to contain 8/9 hazardous substances and most elements contained in these plastics were below their standard thresholds. These elements in plastic samples could be divided as the result into three hazard groups: (1) high hazard group (Sb, Cl, and S); (2) medium hazard group (Cr, Br and Hg); and (3) low hazard groups (Cd, Pb and Sn). Among substances in the high hazard group, element Sb was assessed for its migration because only Sb is regulated in Vietnam in QCVN 12-1: 2011/BYT. Substances of Cl, S, Cr, Br, and Hg (group 1, 2) do not have regulations related to the method of decontamination. Thus, additional health risks need to be assessed using the USEtox model. Finally, this study proposed a screening process to assess the risk of toxicity of elements contained in plastic food containers through ISO 31000:2018.
PubDate: 2023-10-01
- Two weeks dose range-finding and four weeks repeated dose oral toxicity
study of a novel reversible monoamine oxidase B inhibitor KDS2010 in
cynomolgus monkeys-
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Abstract: Abstract A novel reversible monoamine oxidase B inhibitor, KDS2010, has been developed as a therapeutic candidate for neurodegenerative diseases. This study investigated its potential toxicity in non-human primates before human clinical trials. Daily KDS2010 doses (25, 50, or 100 mg/kg) were orally administered to cynomolgus monkeys (1 animal/sex/group, 4 males and 4 females) for 2 weeks to determine the dose range. One male was moribund, and one female was found dead in the 100 mg/kg/day group. One male was also found dead in the 50 mg/kg/day group. The death was considered an adverse effect in both sexes since distal tubules/collecting duct dilation and hypertrophy in the epithelium of the papillary duct were observed in their kidneys. Based on dose range finding results, KDS2010 (10, 20, or 40 mg/kg/day) was administered orally for 4 weeks, and animals were given 2 weeks for recovery. No significant changes were observed during daily clinical observations and macro-and microscopic examinations, including body weight, food consumption, hematology, clinical chemistry, and organ weight. And, the kidney was seen as the primary target organ of KDS2010 in the 2 weeks study, but no adverse effect was observed in the 4 weeks study. Therefore, 40 mg/kg/day is considered the no-observed-adverse-effect level in both sexes of cynomolgus monkeys.
PubDate: 2023-10-01
- Association of immunotoxicological indices with lung cancer biomarkers in
poultry, grape, and rose farming workers-
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Abstract: Abstract Exposure to occupational hazards like dust, pesticides, diesel emission particles, or physical hazards in the agricultural sector is known to cause adverse health effects on farm workers. Our study aimed at addressing the association of immunomodulatory status with plasma levels of lung cancer biomarkers in farming population, attempting to recognition of vulnerable farming group. Blood samples from apparently healthy 51 chicken husbandry, 19 grape orchard, and 21 rose greenhouse workers were subjected to evaluate plasma levels of two representative lung cancer biomarkers, pro-gastrin releasing peptide (Pro-GRP) and cytokeratin fragment 19 (CYFRA 21-1). Peripheral blood mononuclear cells obtained from farmers were used for natural killer (NK) cell phenotyping and cytokines (interferon-gamma, IFN-γ and interleukin-13, IL-13) profiling in the culture supernatant. Compared to the rose greenhouse farmers, the grape orchard and chicken husbandry workers revealed a significantly upregulated plasma Pro-GRP and CYFRA 21-1 level. A low proportion of NK cells was observed among the female grape orchard workers and a lowered IFN- γ:IL-13 ratio was seen in the grape and chicken husbandry workers than the rose workers. Our findings imply that grape orchard and chicken husbandry workers have more disturbed immune homeostasis implicated with augmentation in the levels of lung cancer biomarkers than the rose greenhouse workers.
PubDate: 2023-10-01
- Acute toxicity assessment of nine organic UV filters using a set of
biotests-
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Abstract: UV filters in environmental compartments are a source of concern related to their ecotoxicological effects. However, little is known about UV filters’ toxicity, particularly those released into the environment as mixtures. Acute toxicity of nine organic UV filters benzophenone-1, benzophenone-2, benzophenone-3, 4-methoxy benzylidene camphor, octocrylene, ethylhexyl methoxycinnamate, 2-ethylhexyl salicylate, homosalate, and butyl methoxydibenzoylmethane was determined. UV filter solutions were tested as single, binary, and ternary mixtures of various compositions. Single solutions were tested using a set of bio tests, including tests on saline crustaceans (Artemia franciscana), freshwater crustaceans (Daphnia magna), marine bacteria (Aliivibrio fischeri), and freshwater plants (Lemna minor). The tests represent different stages of the trophic chain, and hence their overall results could be used to risk assessment concerning various water reservoirs. The toxicity of binary and ternary mixtures was analyzed using the standardized Microtox® method. Generally, organic UV filters were classified as acutely toxic. Octocrylene was the most toxic for Arthemia franciscana (LC50 = 0.55 mg L–1) and Daphnia magna (EC50 = 2.66–3.67 mg L–1). The most toxic against freshwater plants were homosalate (IC50 = 1.46 mg L–1) and octocrylene (IC50 = 1.95 mg L–1). Ethylhexyl methoxycinnamate (EC50 = 1.38–2.16 mg L–1) was the most toxic for marine bacteria. The least toxic for crustaceans and plants were benzophenone-1 (EC50 = 6.15–46.78 mg L–1) and benzophenone-2 (EC50 = 14.15–54.30 mg L–1), while 4-methoxy benzylidene camphor was the least toxic for marine bacteria (EC50 = 12.97–15.44 mg L–1). Individual species differ in their sensitivity to the tested organic UV filters. An assessment of the toxicity of mixtures indicates high and acute toxicity to marine bacteria after exposition to a binary mixture of benzophenone-2 with octocrylene, 2-ethylhexyl salicylate, or homosalate. The toxicity of mixtures was lower than single solutions predicting antagonistic interaction between chemicals. Graphical abstract 
PubDate: 2023-10-01
- YPEL3 expression induces cellular senescence via the Hippo signaling
pathway in human breast cancer cells-
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Abstract: Abstract The Hippo pathway is a signaling pathway that controls organ size in animals by regulating cell proliferation and apoptosis. Yes-associated protein 1 (YAP1), an oncogene associated with the development and progression of breast cancer, is downregulated by the Hippo pathway and is associated with the development and progression of breast cancer. Yippee-like 3 (YPEL3) is a target gene of the tumor suppressor protein p53, and its activation has been shown to inhibit cell growth, induce cellular senescence, and suppress tumor cell metastasis. In this study, we found that YAP1 inhibits the expression of YPEL3 expression in breast cancer cells. Furthermore, a decrease in lamin B1, a marker protein of cellular senescence, coupled with the activation of senescence-associated β-galactosidase indicated that upregulating YPEL3 levels through YAP1 downregulation can induce cellular senescence. Additionally, elevated YPEL3 levels resulted in higher levels of oxygen consumption rate in mitochondria, thus promoting apoptosis. This suggests that YPEL3 plays a crucial role in regulating oxidative stress and cell apoptosis in breast cancer cells. Therefore, the interaction between YAP1 and YPEL3 represents a novel mechanism of cellular senescence mediated by the Hippo signaling pathway. Collectively, our findings suggest that the Hippo signaling pathway plays an important role in regulating cellular senescence, which could have implications for the development of new therapeutic strategies for diseases such as cancer.
PubDate: 2023-08-24
DOI: 10.1007/s43188-023-00208-x
- Effects of toxicants on endoplasmic reticulum stress and hepatic cell fate
determination-
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Abstract: Abstract Toxicant-induced injury is a significant global health issue. However, the mechanisms through which toxicants such as carbon tetrachloride, acetaminophen, dimethylformamide, cocaine, and morphine induce the death of multiple cell types and contribute to liver toxicity are highly complex. This phenomenon involves intricate signaling pathways in association with oxidative stress, inflammation, and activation of death receptors, which are closely linked to endoplasmic reticulum (ER) stress. ER stress initially triggers the unfolded protein response, which either promotes cell survival or causes cell death at later times, depending on the severity and duration of the stress. Thus, comprehending the molecular basis governing cell fate determination in the context of ER stress may provide key insights into the prevention and treatment of toxicant-induced injury. This review summarizes our current understanding of agents that trigger different forms of ER stress-mediated cell death, necroptosis, ferroptosis, pyroptosis, and apoptosis, and covers the underlying molecular basis of toxicant-induced ER stress, as well as potential target molecules.
PubDate: 2023-07-26
DOI: 10.1007/s43188-023-00201-4
- Molecular mechanisms of 1,2-dichloroethane-induced neurotoxicity
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Abstract: Abstract The production of industrial solvents and adhesives often utilizes 1,2-dichloroethane (1,2-DCE), a highly toxic halogenated hydrocarbon compound. Occupational 1,2-DCE poisoning occurs frequently and is a public health concern. Exposure to 1,2-DCE can damage the brain, liver, and kidneys. The main and most severe damage caused by exposure to 1,2-DCE is to the nervous system, especially the central nervous system. Current research on 1,2-DCE mainly focuses on the mechanism of brain edema. Several possible mechanisms of 1,2-DCE neurotoxicity have been proposed, including oxidative stress, calcium overload, blood–brain barrier damage, and neurotransmitter changes. This article reviews the research progress on 1,2-DCE neurotoxicity and the mechanism behind it to provide a scientific basis for the prevention and treatment of 1,2-DCE poisoning.
PubDate: 2023-07-13
DOI: 10.1007/s43188-023-00197-x
- Effects of grape seed proanthocyanidin extract on side effects of
high-dose methylprednisolone administration in male rats-
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Abstract: Abstract In this study, we investigated the effects of grape seed proanthocyanidin extract (GSPE) against the side effects of high-dose administration of methylprednisolone (MP) in male rats. A total of 32 adult Wistar male albino rats were divided into four groups: (1) control (CON), received standard food only; (2) MP, received standard food + intraperitoneal injection of 60 mg/kg MP on day 7; (3) GSPE, received standard food + 200 mg/kg/day GSPE; and (4) MP + GSPE, received standard food + 200 mg/kg/day of GSPE + intraperitoneal injection of 60 mg/kg MP on day 7. All animals in the GSPE and GSPE + MP groups were treated once a day by oral gavage for 14 consecutive days. The feed intake of rats in the MP and MP + GSPE groups decreased significantly by 24.14% and 13.52%, respectively (p < 0.05). Administration of MP resulted in significant increases in serum concentrations of blood urea nitrogen (p < 0.001), glucose (p < 0.01), alkaline phosphatase, and adrenocorticotropic hormone (p < 0.05). High-dose MP administration significantly reduced catalase (p < 0.001) and glutathione peroxidase (p < 0.05) concentrations in the liver and kidney tissues of rats, while glutathione concentrations were only reduced in liver tissue (p < 0.05). The expression levels of Bcl-2 and TNF-α in liver, kidney, and testicular tissue were significantly increased, while the expression levels of caspase-3 were reduced (p < 0.001). Furthermore, sperm concentration was significantly affected by GSPE in rats induced by high-dose MP, and sperm loss was significantly reduced in MP + GSPE (p < 0.05). These findings suggest that GSPE could be useful as a supplement to alleviate MP-induced toxicity in rats.
PubDate: 2023-07-07
DOI: 10.1007/s43188-023-00196-y
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