The Toxic Mechanism of Gliotoxins and Biosynthetic Strategies for Toxicity Prevention

Gliotoxin is a kind of epipolythiodioxopiperazine derived from different fungi that is characterized by a disulfide bridge. Gliotoxins can be biosynthesized by a gli gene cluster and regulated by a positive GliZ regulator. Gliotoxins show cytotoxic effects via the suppression the function of macrophage immune function, inflammation, antiangiogenesis, DNA damage by ROS production, peroxide damage by the inhibition of various enzymes, and apoptosis through different signal pathways. In the other hand, gliotoxins can also be beneficial with different doses. Low doses of gliotoxin can be used as an antioxidant, in the diagnosis and treatment of HIV, and as an anti-tumor agent in the future. Gliotoxins have also been used in the control of plant pathogens, including Pythium ultimum and Sclerotinia sclerotiorum. Thus, it is important to elucidate the toxic mechanism of gliotoxins. The toxic mechanism of gliotoxins and biosynthetic strategies to reduce the toxicity of gliotoxins and their producing strains are summarized in this review.

Reproductive Toxicity Induced By Benzo[a]pyrene Exposure: First Exploration Highlighting The Multi-stage Molecular Mechanism In Female Scallop Chlamys Farreri

Reproductive toxicity induced by Benzo[a]pyrene (B[a]P) exposure have received great ecotoxicological concerns. However, huge gaps on molecular mechanism still exist in bivalves. In this study, reproduction-related indicators during reproductive periods (proliferative, growth, mature, and spawn stage) were investigated in female scallops Chlamys farreri, which under gradient concentration of B[a]P at 0, 0.04, 0.4 and 4 μg/L. To elucidate the potential molecular mechanisms of reproductive toxicology, a multi-stage ovarian transcriptome analysis under 4 μg/L B[a]P exposure was also conducted. The results indicated that life-cycle exposure to 0.4 and 4 μg/L B[a]P had significantly decreased GSI and sex steroid levels. Even 0.04 μg/L B[a]P could play the wicked role on DNA integrity at mature and spawn stages. Ovarian histological sections showed the inhibitions on oocyte maturation and ovulation of B[a]P with dose-dependent effects. Through the functional enrichment analysis of DEGs from transcriptome data, 18 genes involved in endocrine disruption effects, DNA damage and repair, and oogenesis damage were selected and further determined by qRT-PCR. The down-regulate of steroidogenic and estrogen signaling pathways genes indicated the endocrine disruption mechanisms by B[a]P, which emphasized the functions of receptor independent and dependent pathways under B[a]P exposure. The variation of DNA single strand break and repair gene expressions implied there might exist the similar toxic mechanism with that in vertebrates. Gene expression data involved in cell cycle, apoptosis and cell adhesion exhibited the possibly toxic mechanisms of oogenesis caused by B[a]P. Taken together, this study is a pioneer to take advantage of genome-wide transcriptomic analysis and its corresponding reproductive indicators to explore the toxic mechanism under B[a]P exposure in bivalves. Meanwhile, some selected genes were firstly identified in bivalves, and the expression data might be useful in establishing new hypotheses and discovering new biomarkers for marine biomonitoring.

Whole Cigarette Smoke Condensates Induce Accumulation of Amyloid Beta Precursor Protein with Oxidative Stress in Murine Astrocytes

Although cigarette smoking has been postulated to be a potential risk factor for Alzheimer’s disease (AD), the toxic mechanism is still unclear. Additionally, astrocytes have been identified as a potential target, given they play multiple roles in maintaining normal brain function. In this study, we explored the toxic mechanism of whole cigarette smoke condensates (WCSC) using murine astrocytes. Cell proliferation, the percentage of cells in the G2/M phase, and LDH concentrations in the cell supernatants were all reduced in WCSC-treated cells. In addition, oxidative stress was induced, together with shortening of processes, structural damage of organelles, disturbances in mitochondrial function, blockage of autophagic signals, accumulation of amyloid β precursor protein, and loss of chemotactic functions. Based on these results, we hypothesize that dysfunction of astrocytes may contribute to the occurrence of cigarette-smoking-induced AD.