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Long-Term Toxicity and Regulations for Bioactive-Loaded Nanomedicines
Published in Mahfoozur Rahman, Sarwar Beg, Mazin A. Zamzami, Hani Choudhry, Aftab Ahmad, Khalid S. Alharbi, Biomarkers as Targeted Herbal Drug Discovery, 2022
Iqbal Ahmad, Sobiya Zafar, Shakeeb Ahmad, Suma Saad, S. M. Kawish, Sanjay Agarwal, Farhan Jalees Ahmad
Furthermore, reduced particle size and higher surface area collectively generate more ROS as compared to larger particles (Brown et al., 2000) and hence may produce more genotoxicity. Type of target in the phases of the cell cycle, mutagen, DNA replication, and methods of DNA repairment collectively develop a genotoxic effect. For example, NMs may alter the strands of DNA in G1-phase, may negatively affect the formation of spindle fibers in phase G2. In addition, NMs on getting the right to permeate through the nuclear membrane may also affect the chromatin during interphase or mitosis. Examples of NMs induced ROS are; singlet oxygen, superoxide, hydrogen peroxide, hydroxyl radicals (Fubini and Hubbard, 2003).
Approaches for Identification and Validation of Antimicrobial Compounds of Plant Origin: A Long Way from the Field to the Market
Published in Mahendra Rai, Chistiane M. Feitosa, Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
Lívia Maria Batista Vilela, Carlos André dos Santos-Silva, Ricardo Salas Roldan-Filho, Pollyanna Michelle da Silva, Marx de Oliveira Lima, José Rafael da Silva Araújo, Wilson Dias de Oliveira, Suyane de Deus e Melo, Madson Allan de Luna Aragão, Thiago Henrique Napoleão, Patrícia Maria Guedes Paiva, Ana Christina Brasileiro-Vidal, Ana Maria Benko-Iseppon
For the detection of the in vitro limit cytotoxic concentration, one out of four cytogenetic tests (RICC, RPD, CBPI or RI) with sufficient compound concentration to induce cytotoxicity is recommended by ICH and OECD (OECD 2016a). However, there are divergences in the selection of the maximum concentration used for in vitro tests. FDA and EMA S2 (R1) guides recommend maximum concentrations of 1 mM or 500 µg/mL (Kirkland and Fowler 2010), while OECD TGs 487 and 473 recommend 10 mM or 5000 µg/mL. Additionally, in some cases, as plant extracts, the composition of the tested substance is not well defined (OECD 2016a). On the other hand, all guides recommend that genotoxic analysis use concentrations that do not exceed 50% cytotoxicity (FDA 2012; OECD 2016a; OECD 2016b).
Dietary Fat and Colon Cancer
Published in Herman Autrup, Gary M. Williams, Experimental Colon Carcinogenesis, 2019
Rapid progress has been made in basic concepts concerning carcinogenesis.1,2-3 There are agents that are genotoxic, which by definition interact with the gene to yield an abnormal genetic material. The second broad class of agents acts by epigenetic mechanisms and tends to increase the development of lesions initiated by genotoxic carcinogens. This list includes classic tumor promoters which exhibit their effect after the action of a genotoxic carcinogen and cocarcinogens which operate at the same time as genotoxic carcinogens and can alter the metabolism of a genotoxic agent with an increased ratio of activation/detoxification metabolites.
Occupational risk assessment of exposure to metals in chrome plating workers
Published in Drug and Chemical Toxicology, 2022
Cristina Deuner Muller, Solange Cristina Garcia, Natália Brucker, Gabriela Goethel, Elisa Sauer, Larissa Machado Lacerda, Evandro Oliveira, Thereza Luciano Trombini, Aline Belem Machado, Anelise Pressotto, Virginia Cielo Rech, Cláudia Regina Klauck, Luciano Basso da Silva, Adriana Gioda, Luciane Rosa Feksa
The present study aimed to evaluate the occupational risk of exposure to metals in chrome plating workers. For that, the inflammatory expression such as β-2 integrin, intercellular adhesion molecule-1 (ICAM-1), and L-selectin was determined in lymphocytes. The comet and micronucleus assays were used for detecting the possible genotoxic effects. Lipid peroxidation was assessed by malondialdehyde (MDA) levels, and protein oxidation was evaluated by the protein carbonyl (PCO) assay to determine the possible involvement of oxidative stress. The possible influences of confounding factors such as age, smoking, alcohol consumption, and exposure time were also analyzed. Therefore, this present study aimed to identify critical metabolic targets on occupational exposure to determine biomarkers of effect, assisting in the diagnosis and monitoring of workers of the chrome plating industry.
Exploring graphene-based materials’ genotoxicity: inputs of a screening method
Published in Nanotoxicology, 2021
Salma Achawi, Ludovic Huot, Fabrice Nesslany, Jérémie Pourchez, Sophie Simar, Valérie Forest, Bruno Feneon
Briefly, aneugenicity, clastogenicity or mutagenicity are major genotoxicity mechanisms. For aneugenicity, genotoxicants act primarily on non-DNA targets (microtubule, centrosome or kinetochore (More et al. 2021)) or cause damage to the mitosis apparatus, leading to improper chromosome segregation (Parry et al. 1996, 2002). For clastogenicity, structural chromosome aberrations such as chromatid/chromosome breaks occur (Bignold 2009). Clastogenic agents can covalently bind to DNA or enzymes, leading to chromosome breakage. Mutagenicity corresponds to the induction of DNA mutations (Kumar et al. 2018), either by direct interaction with DNA or chromatin or by indirect mechanisms, such as through generation of reactive oxygen species or inflammation (DeMarini 2019). Genotoxicity is associated to serious health effects, the first one being cancer (Phillips and Arlt 2009): some genotoxic agents can indeed cause mutations that can eventually lead to malign tumor. Hence, most carcinogenic chemicals are genotoxic (Hayashi 1992), which make the measurement of this endpoint critical for hazard assessment.
Cytotoxicity and antigenotoxicity evaluation of acetylshikonin and shikonin
Published in Drug and Chemical Toxicology, 2021
Ramona Figat, Anna Zgadzaj, Sylwia Geschke, Patrycja Sieczka, Agnieszka Pietrosiuk, Sylwester Sommer, Agata Skrzypczak
Another potential of naphthoquinones is antigenotoxic activity. However, there are only a few reports on the antigenotoxic action of naphthoquinones (Papageorgiou et al.1999, Bhatia et al.2011). In the human environment, there is an increased exposure to genotoxic agents causing DNA damage. Therefore a lot of contemporary research work is directed towards searching for safe and potent antigenotoxic compounds which are capable of removing or reducing genotoxic effects. Our previous study revealed promising results of SH and ASH against the genotoxicity of 2-aminoantracene and the photogenotoxicity of chlorpromazine on Salmonella typhimurium cells in umu-test (Skrzypczak et al.2015). We decided to continue our research on eukaryotic cells in a micronucleus assay.