Departamento de Farmacología, Instituto de Ciencias del Mar (ICIMAR), Loma 14, Alturas del Vedado, Plaza de la Revolución, La Habana 10600, Cuba.
Dirección Médica, Laboratorios Liomont S.A. de C.V., Carretera México-Toluca 5420, Ciudad de México 05320, Mexico.
Mar Drugs. 2020 Nov 19;18(11):566. doi: 10.3390/md18110566.
The aim of the present work was to evaluate the effects of hydroethanolic extract, its polyphenolic fraction and thalassiolin B on the activity of phase I metabolizing enzymes as well as their antimutagenic effects. Spectrofluorometric techniques were used to evaluate the effect of tested products on rat and human CYP1A and CYP2B activity. The antimutagenic effect of tested products was evaluated in benzo[a]pyrene (BP)-induced mutagenicity assay by an Ames test. Finally, the antimutagenic effect of (100 mg/kg) was assessed in BP-induced mutagenesis in mice. The tested products significantly ( < 0.05) inhibit rat CYP1A1 activity, acting as mixed-type inhibitors of rat CYP1A1 (Ki = 54.16 ± 9.09 μg/mL, 5.96 ± 1.55 μg/mL and 3.05 ± 0.89 μg/mL, respectively). Inhibition of human CYP1A1 was also observed (Ki = 197.1 ± 63.40 μg/mL and 203.10 ± 17.29 μg/mL for the polyphenolic fraction and for thalassiolin B, respectively). In addition, the evaluated products significantly inhibit ( < 0.05) BP-induced mutagenicity in vitro. Furthermore, oral doses of (100 mg/kg) significantly reduced ( < 0.05) the BP-induced micronuclei and oxidative damage, together with an increase of reduced glutathione, in mice. In summary, metabolites exhibit antigenotoxic activity mediated, at least, by the inhibition of CYP1A1-mediated BP biotransformation, arresting the oxidative and mutagenic damage. Thus, the metabolites of may represent a potential source of chemopreventive compounds for the adjuvant therapy of cancer.
本研究旨在评估水-乙醇提取物、多酚部分和 Thalassiolin B 对 I 相代谢酶活性的影响及其抗突变作用。荧光光谱技术用于评估测试产品对大鼠和人 CYP1A 和 CYP2B 活性的影响。通过 Ames 试验评估测试产品对苯并[a]芘（BP）诱导致突变性的抗突变作用。最后，在 BP 诱导的小鼠突变试验中评估了（100mg/kg）的抗突变作用。测试产品显著（<0.05）抑制大鼠 CYP1A1 活性，作为大鼠 CYP1A1 的混合抑制剂（Ki 值分别为 54.16±9.09μg/mL、5.96±1.55μg/mL 和 3.05±0.89μg/mL）。还观察到对人 CYP1A1 的抑制作用（多酚部分和 Thalassiolin B 的 Ki 值分别为 197.1±63.40μg/mL 和 203.10±17.29μg/mL）。此外，评估的产品显著（<0.05）抑制体外 BP 诱导的致突变性。此外，（100mg/kg）的口服剂量可显著降低（<0.05）BP 诱导的微核和氧化损伤，并增加小鼠的还原型谷胱甘肽。综上所述，代谢物表现出抗原毒性活性，至少通过抑制 CYP1A1 介导的 BP 生物转化来介导，从而阻止氧化和突变损伤。因此，的代谢物可能代表用于癌症辅助治疗的化学预防化合物的潜在来源。
