Study on the Enhancement of Immune Function of Astaxanthin from Haematococcus pluvialis

This study was aimed at investigating the effect of astaxanthin on the immune function and its safety in mice. It was administered once daily at low, medium and high doses (4.2, 8.35, 16.70 mg/kg BW) to mice for 30 days. Subsequently, the spleen and thymus index, spleen lymphocyte transformation activity, delayed allergy reaction, amounts of antibody-producing cells, half-hemolytic value HC50, carbon particle clearance rate, macrophage phagocytosis, and natural killer cell (NK) activity were determined. Acute oral toxicity and genotoxicity tests were conducted to evaluate the safety of astaxanthin. Compared with the control group, medium and high doses of astaxanthin significantly increased the proliferation and transformation activities of spleen lymphocytes, activities of antibody-producing cells, serum hemolysin levels, and carbon particle clearance rate in mice (phagocytic index). High doses significantly improved delayed allergy reaction and NK cell activity. Results of acute oral toxicity and genotoxicity tests were negative. Gross anatomical observations and histopathological examination showed no abnormal changes associated with the treatments. In the article, it is confirmed that astaxanthin treatments significantly improve immune functions and show no toxic effects in the experimental doses.

Analysis of mutagenic components of oxidative hair dyes with the Ames test

Oxidative hair dyes consist of two components (I and II) that are mixed before use. Aromatic amines in component I and their reaction with hydrogen peroxide after mixing them with component II have been of primary concern. In addition, two in vitro genotoxicity assays are still required for the approval of the final products of oxidative hair dyes in China, and the substance in the oxidative hair dye that causes the high rate of positive results in genotoxicity tests, especially the Ames test, has not been fully elucidated. In this study, we analyzed the formulation of 55 different oxidative hair dyes from 7 color series and performed Ames tests in the strain TA98 with the S9 mix (oxidative hair dyes No. 1–30) and in strain TA97a without the S9 mix (oxidative hair dyes No. 31–55). We found that toluene-2,5-diamine sulfate (2,5-diaminotoluene sulfate, DATS) in component I may be the cause of mutagenicity in TA98, and hydrogen peroxide in component II may be the cause of mutagenicity in TA97a, and their positive concentrations were consistent with those that we calculated from Ames tests. The results suggest that the positive results for the oxidative hair dye in the Ames test were inevitable because of the existence of DATS in component I and of hydrogen peroxide in component II. Therefore, we should carry out safety assessments on each raw material and carry out risk assessments on the final products of oxidative hair dyes instead of genotoxicity tests in China.

Pyrostegia Genus: An Update Review of Phytochemical Compounds and Pharmacological Activities

The Pyrostegia genus of the Bignoniaceae family. This genus is consists of four species and indigenous to South America. The plants of this genus are being applied in traditional uses in Brazil. This review of the scientific work about Pyrostegia genus was highlighting and updating their traditional uses, phytochemical compounds, pharmacological activities, genotoxicity tests, and toxicity studies. The information was systematical with the scientific literature database, including Elsevier, Google Scholar, PubMed, Science Direct, and Scopus, and Springer. The literature survey showed various traditional uses of Pyrostegia genus, such as drugs to therapy diarrhea, coughing, vitiligo, jaundice, and respiratory system-related diseases, i.e., colds, coughs, and bronchitis. Phytochemical compounds from the Pyrostegia genus have shown the presence of flavonoids, phenolic compounds, phenylpropanoids, phenylethanoid glycosides, triterpenes, and sterols. The extract of Pyrostegia genus has a variety of pharmacology actions, i.e., antioxidant, antimicrobial, antifungal, anti-inflammatory, wound healing activities, antinociceptive, analgesic, vasorelaxant activities, antitumor, cytotoxic, hepatoprotective, antitussive, anthelmintic, hyperpigmented, treatment of sickness behavior, estrogenic, antihypertensive, and immunomodulatory. Pyrostegia genus is considerably used in traditional medicines and has various pharmacological activities. However, most species of Pyrostegia genus must be further researched concerning its chemical constituents and pharmacological activities.

Systemic assessment of pesticide genotoxicity

Изучена генотоксичность более 200 технических продуктов (ТП) пестицидов. Разработан алгоритм оценки эквивалентности ТП оригинальным действующим веществам (ДВ) по критерию «мутагенность». Обоснована необходимость изучения генотоксической активности комбинаций ДВ пестицидов. Установлены ограничения тестов на генотоксичность, обусловленные токсичностью пестицидов разных химических классов. Выявлена зависимость ингибирующего эритропоэз действия триазоловых пестицидов от структуры ДВ. Изучено влияние и предложен общий механизм действия карбендазима на процессы кариокинеза, экструзии ядер и цитокинеза в эритроидных клетках костного мозга млекопитающих. Разработаны критерии экспертной оценки мутагенности пестицидов. The genotoxicity of more than 200 technical grade active ingredients (TGAI) of pesticides has been studied. An algorithm for evaluating the equivalence of TGAIs to the original active ingredients upon the criterion of “mutagenicity” has been developed. The necessity of studying the genotoxic activity of the combinations of pesticide active ingredients was substantiated. Limitations of the genotoxicity tests due to toxicity of pesticides of different chemical classes have been established. The dependence of the erythropoiesis-inhibiting action of triazole pesticides on the structure of the active ingredient was revealed. The effects and the general mechanism of the carbendazim action on the processes of karyokinesis, extrusion of nuclei and cytokinesis in mammalian bone marrow erythroid cells were studied. The criteria for expert evaluation of pesticide mutagenicity have been developed.

Antiproliferative and Genotoxic Action of an Underexploited Organoteluran Derivative on Sarcoma 180 Cells

Background: The search for novel metallic chemical compounds with toxicogenic effects have been of great importance for more efficient cancer treatment. Objective: The study evaluated the cytotoxic, genotoxic and mutagenic activity of organoteluran RF07 in S-180 cell line. Methods: The bioassays used were cell viability with 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, evaluation of apoptosis and necrosis using fluorescence and flow cytometry, cytokinesis-block micronucleus test and comet assay. The compound was tested at 1; 2.5 and 5 µM. Results: The results showed the cytotoxicity of RF07 at concentrations of 2.5, 5, 10 and 20 µM when compared to the negative control. For genotoxicity tests, RF07 showed effects in all concentrations assessed by increased index and frequencies of damage and mutagenic alterations. The compound was also cytotoxic due to the significant decrease in nuclear division index, with significant values of apoptosis and necrosis. The results of fluorescence and flow cytometry showed apoptosis as the main type of cell death caused by RF07 at 5 µM, which is thought to avoid an aggressive immune response of the organism. Conclusion: In addition to cytotoxic and genotoxic effects, RF07 creates good perspectives for future antitumor formulations.

Chemical carcinogen safety testing: OECD expert group international consensus on the development of an integrated approach for the testing and assessment of chemical non-genotoxic carcinogens

While regulatory requirements for carcinogenicity testing of chemicals vary according to product sector and regulatory jurisdiction, the standard approach starts with a battery of genotoxicity tests (which include mutagenicity assays). If any of the in vivo genotoxicity tests are positive, a lifetime rodent cancer bioassay may be requested, but under most chemical regulations (except plant protection, biocides, pharmaceuticals), this is rare. The decision to conduct further testing based on genotoxicity test outcomes creates a regulatory gap for the identification of non-genotoxic carcinogens (NGTxC). With the objective of addressing this gap, in 2016, the Organization of Economic Cooperation and Development (OECD) established an expert group to develop an integrated approach to the testing and assessment (IATA) of NGTxC. Through that work, a definition of NGTxC in a regulatory context was agreed. Using the adverse outcome pathway (AOP) concept, various cancer models were developed, and overarching mechanisms and modes of action were identified. After further refining and structuring with respect to the common hallmarks of cancer and knowing that NGTxC act through a large variety of specific mechanisms, with cell proliferation commonly being a unifying element, it became evident that a panel of tests covering multiple biological traits will be needed to populate the IATA. Consequently, in addition to literature and database investigation, the OECD opened a call for relevant assays in 2018 to receive suggestions. Here, we report on the definition of NGTxC, on the development of the overarching NGTxC IATA, and on the development of ranking parameters to evaluate the assays. Ultimately the intent is to select the best scoring assays for integration in an NGTxC IATA to better identify carcinogens and reduce public health hazards.

Micronucleus Assay: The State of Art, and Future Directions

During almost 40 years of use, the micronucleus assay (MN) has become one of the most popular methods to assess genotoxicity of different chemical and physical factors, including ionizing radiation-induced DNA damage. In this minireview, we focus on the position of MN among the other genotoxicity tests, its usefulness in different applications and visibility by international organizations, such as International Atomic Energy Agency, Organization for Economic Co-operation and Development and International Organization for Standardization. In addition, the mechanism of micronuclei formation is discussed. Finally, foreseen directions of the MN development are pointed, such as automation, buccal cells MN and chromothripsis phenomenon.