Studies on the in vivo and in vitro mutagenicity and the lipid peroxidation of chlorinated surface (drinking) water in rats and metabolically competent human cells

2002 ◽  
Vol 513 (1-2) ◽  
pp. 151-157 ◽  
Author(s):  
W.Q. Lu ◽  
X.N. Chen ◽  
F. Yue ◽  
C. Jenter ◽  
R. Gminski ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Drinking Water ◽  
Human Cells

Chemosensitizing Activity of Histone Deacetylases Inhibitory Cyclic Hydroxamic Acids for Combination Chemotherapy of Lymphatic Leukemia

2018 ◽  
Vol 18 (4) ◽  
pp. 365-371 ◽  
Author(s):  
Denis V. Mishchenko ◽  
Margarita E. Neganova ◽  
Elena N. Klimanova ◽  
Tatyana E. Sashenkova ◽  
Sergey G. Klochkov ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Acute Toxicity ◽  
Histone Deacetylases ◽  
Hydroxamic Acids ◽  
Water Soluble ◽  
Male Rat ◽  
Hybrid Male ◽  
Cyclic Hydroxamic Acids

Background: Anti-tumor effect of hydroxamic acid derivatives is largely connected with its properties as efficient inhibitors of histone deacetylases, and other metalloenzymes involved in carcinogenesis. Objective: The work was aimed to (i) determine the anti-tumor and chemosensitizing activity of the novel racemic spirocyclic hydroxamic acids using experimental drug sensitive leukemia P388 of mice, and (ii) determine the structure-activity relationships as metal chelating and HDAC inhibitory agents. Method: Outbreed male rat of 200-220 g weights were used in biochemical experiments. In vivo experiments were performed using the BDF1 hybrid male mice of 22-24 g weight. Lipid peroxidation, Fe (II) -chelating activity, HDAC fluorescent activity, anti-tumor and anti-metastatic activity, acute toxicity techniques were used in this study. Results: Chemosensitizing properties of water soluble cyclic hydroxamic acids (CHA) are evaluated using in vitro activities and in vivo methods and found significant results. These compounds possess iron (II) chelating properties, and slightly inhibit lipid peroxidation. CHA prepared from triacetonamine (1a-e) are more effective Fe (II) ions cheaters, as compared to CHA prepared from 1- methylpiperidone (2a-e). The histone deacetylase (HDAC) inhibitory activity, lipophilicity and acute toxicity were influenced by the length amino acids (size) (Glycine < Alanine < Valine < Leucine < Phenylalanine). All compounds bearing spiro-N-methylpiperidine ring (2a-e) are non-toxic up to 1250 mg/kg dose, while compounds bearing spiro-tetramethylpiperidine ring (1a-e) exhibit moderate toxicity which increases with increasing lipophility, but not excite at 400 mg/kg. Conclusion: It was shown that the use of combination of non-toxic doses of cisplatin (cPt) or cyclophosphamide with CHA in most cases result in the appearance of a considerable anti-tumor effect of cytostatics. The highest chemosensitizing activity with respect to leukemia Р388 is demonstrated by the CHA derivatives of Valine 1c or 2c.

scholarly journals Amelioration of lipid peroxidation in vivo and in vitro by Satureja khozestanica essential oil in alloxan-induced diabetic rats

2014 ◽  
Vol 13 (1) ◽  
Author(s):  
Hassan Ahmadvand ◽  
Majid Tavafi ◽  
Ali Khosrowbeygi ◽  
Gholamreza Shahsavari ◽  
Maryam Hormozi ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Essential Oil ◽  
Diabetic Rats

scholarly journals Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Miao-Miao Zhao ◽  
Wei-Li Yang ◽  
Fang-Yuan Yang ◽  
Li Zhang ◽  
Wei-Jin Huang ◽  
...  
Keyword(s):  
Drug Development ◽  
Cathepsin L ◽  
Human Cells ◽  
New Drugs ◽  
Disease Course ◽  
Promising Target ◽  
First Time

AbstractTo discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.

The phylogenetically invariant ACAGAGA and AGC sequences of U6 small nuclear RNA are more tolerant of mutation in human cells than in Saccharomyces cerevisiae

1993 ◽  
Vol 13 (9) ◽  
pp. 5377-5382
Author(s):  
B Datta ◽  
A M Weiner
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transient Expression ◽  
Human Cells ◽  
Mrna Splicing ◽  
Small Nuclear Rna ◽  
Transient Expression Assay ◽  
U6 Snrna ◽  
Nuclear Rna

U6 small nuclear RNA (snRNA) is the most highly conserved of the five spliceosomal snRNAs that participate in nuclear mRNA splicing. The proposal that U6 snRNA plays a key catalytic role in splicing [D. Brow and C. Guthrie, Nature (London) 337:14-15, 1989] is supported by the phylogenetic conservation of U6, the sensitivity of U6 to mutation, cross-linking of U6 to the vicinity of the 5' splice site, and genetic evidence for extensive base pairing between U2 and U6 snRNAs. We chose to mutate the phylogenetically invariant 41-ACAGAGA-47 and 53-AGC-55 sequences of human U6 because certain point mutations within the homologous regions of Saccharomyces cerevisiae U6 selectively block the first or second step of mRNA splicing. We found that both sequences are more tolerant to mutation in human cells (assayed by transient expression in vivo) than in S. cerevisiae (assayed by effects on growth or in vitro splicing). These differences may reflect different rate-limiting steps in the particular assays used or differential reliance on redundant RNA-RNA or RNA-protein interactions. The ability of mutations in U6 nucleotides A-45 and A-53 to selectively block step 2 of splicing in S. cerevisiae had previously been construed as evidence that these residues might participate directly in the second chemical step of splicing; an indirect, structural role seems more likely because the equivalent mutations have no obvious phenotype in the human transient expression assay.

The potential reproductive effects of exposure of domestic ruminants to endocrine disrupting compounds

2002 ◽  
Vol 74 (1) ◽  
pp. 3-12 ◽  
Author(s):  
M.L. Boerjan ◽  
S. Freijnagel ◽  
S.M. Rhind ◽  
G.A.L. Meijer
Keyword(s):  
Drinking Water ◽  
Reproductive Function ◽  
Endocrine Disrupting Compounds ◽  
Laboratory Animals ◽  
Domestic Ruminants ◽  
Reproductive Effects ◽  
Endocrine Disrupting ◽  
Contaminated Food

AbstractChemical compounds that mimic or block some of the actions of the steroid hormone oestradiol, have created public concern primarily because of potential adverse reproductive effects in wildlife and humans. Many studies, in vivo and in vitro, have revealed abnormal reproductive function following exposure to these compounds. The number of chemicals known to have the potential to modulate endocrine functions is increasing. In contrast to humans and wildlife, the potential reproductive effects of exposure of domestic animals to endocrine disrupting compounds (EDC) have been studied little. The aim of this overview is to evaluate the possible contribution of EDC to reproductive failure in domestic ruminants.Sources and classes of EDC are discussed as well as their structure and the modes of hormone disruption. Endocrine disrupting agents may interfere with the reproductive processes of both males and females at several points of the reproductive cycle and through a range of physiological mechanisms. Extrapolating from the results obtained with laboratory animals, the mechanisms whereby infertility in domestic ruminants might be expressed by exposure to EDC through contaminated food and drinking water are addressed.A preliminary risk assessment is included and it is concluded that under certain circumstances there may be a significantly enhanced intake of oestrogenic hormones and EDC through sewage-contaminated water or soil-contaminated herbage. The physiological consequences for domestic ruminants of EDC ingestion, at the rates estimated, are largely unknown. However, the levels of exposure to oestrogenic hormones and phthalates in grazing ruminants are such that when studying fertility problems in high-yielding dairy cattle the impacts of exposure to endocrine disruptors via the food and drinking water cannot be neglected.

Phytochemical analysis and nephroprotective effect of cactus (Opuntia ficus-indica) cladodes on sodium dichromate-induced kidney injury in rats

2019 ◽  
Vol 44 (3) ◽  
pp. 239-247
Author(s):  
Mbarka Hfaiedh ◽  
Dalel Brahmi ◽  
Mohamed Nizar Zourgui ◽  
Lazhar Zourgui
Keyword(s):  
Lipid Peroxidation ◽  
Ascorbic Acid ◽  
Antioxidant Activities ◽  
Antioxidant Properties ◽  
Wistar Rat ◽  
Phytochemical Analysis ◽  
Sodium Dichromate ◽  
Opuntia Ficus Indica

Environmental and occupational exposure to chromium compounds, especially hexavalent chromium, is widely recognized as potentially nephrotoxic in humans and animals. The present study aimed to assess the efficacy of cactus (Opuntia ficus-indica) against sodium dichromate-induced nephrotoxicity, oxidative stress, and genotoxicity. Cactus cladodes extract (CCE) was phytochemically studied and tested in vitro for its potential antioxidant activities. Additionally, the preventive effect of CCE against sodium dichromate-induced renal dysfunction in a Wistar rat model (24 rats) was evaluated. For this purpose, CCE at a dose of 100 mg/kg was orally administered, followed by 10 mg/kg sodium dichromate (intraperitoneal injection). After 40 days of treatment, the rats were sacrificed, and the kidneys were excised for histological, lipid peroxidation, and antioxidant enzyme analyses. The phenol, flavonoid, tannin, ascorbic acid, and carotenoid contents of CCE were considered to be important. Our analyses showed that 1 mL of CCE was equivalent to 982.5 ± 1.79 μg of gallic acid, 294.37 ± 0.84 μg of rutin, 234.78 ± 0.24 μg of catechin, 204.34 ± 1.53 μg of ascorbic acid, and 3.14 ± 0.51 μg of β-carotene. In vivo, pretreatment with CCE was found to provide significant protection against sodium dichromate-induced nephrotoxicity by inhibiting lipid peroxidation, preserving normal antioxidant activities, and protecting renal tissues from lesions and DNA damage. The nephroprotective potential of CCE against sodium dichromate toxicity might be due to its antioxidant properties.

scholarly journals Taurine Attenuates Carcinogenicity in Ulcerative Colitis-Colorectal Cancer Mouse Model

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Guifeng Wang ◽  
Ning Ma ◽  
Feng He ◽  
Shosuke Kawanishi ◽  
Hatasu Kobayashi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Drinking Water ◽  
Mouse Model ◽  
Histopathological Examination ◽  
Tumor Formation ◽  
Water Model ◽  
Control Group ◽  
Ki 67

Taurine (2-aminoethane-sulfonic acid) is a type of amino acids and has numerous physiological and therapeutic functions, including anti-inflammation. However, there are few studies on the anticancer action of taurine. Our previous studies have demonstrated that taurine exhibits an apoptosis-inducing effect on human nasopharyngeal carcinoma cells in vitro. In this study, we have investigated whether taurine has an anticancer effect, using azoxymethane (AOM)/sulfate sodium (DSS)- induced mouse model for colon carcinogenesis. All mice, except those in control group, received a single intraperitoneal injection of AOM and DSS in the drinking water for 7 days twice, with 1-week interval. After the first DSS treatment, mice were given distilled water (model group) or taurine in the drinking water (taurine group) ad libitum. No tumor was observed in the control group. Taurine significantly suppressed AOM+DSS-induced tumor formation. Histopathological examination revealed AOM/DSS treatment induced colon cancer in all mice (8/8, 100%), and taurine significantly inhibited the progression of colon cancer (4/9, 44.4%). Taurine significantly attenuated cell proliferation in cancer tissues detected by Ki-67 staining. Taurine significantly increased the levels of an apoptosis marker cleaved caspase-9 and tumor suppressor protein PTEN. This is the first study that demonstrated that taurine significantly reduced carcinogenicity in vivo using AOM/DSS-induced colon cancer mouse model.

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