Department of Medical Biochemistry, Faculty of Medicine, University of Latvia, 1004 Riga, Latvia.
Genetics and Bioinformatics, Institute of Biology, University of Latvia, 1004 Riga, Latvia.
Toxins (Basel). 2023 Feb 17;15(2):165. doi: 10.3390/toxins15020165.
Envenomation by animal venoms remains a serious medical and social problem, especially in tropical countries. On the other hand, animal venoms are widely used as a source of biologically active compounds for the development of novel drugs. Numerous derivatives of animal venoms are already used in clinical practice. When analysing the mechanisms of action of animal venoms, attention is usually focused on the main target of the venom's enzymes and peptides such as neurotoxic, cytotoxic or haemorrhagic effects. In the present review, we would like to draw attention to the "hidden" effects of animal venoms and their derivatives in regard to DNA damage and/or protection against DNA damage. Alkaloids and terpenoids isolated from sponges such as avarol, ingenamine G or variolin B manifest the capability to bind DNA and produce DNA breaks. Trabectidin, isolated from a sea squirt, also binds and damages DNA. A similar action is possible for peptides isolated from bee and wasp venoms such as mastoparan, melectin and melittin. However, DNA lesions produced by the crude venoms of jellyfish, scorpions, spiders and snakes arise as a consequence of cell membrane damage and the subsequent oxidative stress, whereas certain animal venoms or their components produce a genoprotective effect. Current research data point to the possibility of using animal venoms and their components in the development of various potential therapeutic agents; however, before their possible clinical use the route of injection, molecular target, mechanism of action, exact dosage, possible side effects and other fundamental parameters should be further investigated.
动物毒液引起的中毒仍然是一个严重的医学和社会问题,特别是在热带国家。另一方面,动物毒液被广泛用作开发新型药物的生物活性化合物的来源。许多动物毒液的衍生物已经在临床实践中使用。在分析动物毒液的作用机制时,通常会关注毒液酶和肽的主要靶标,如神经毒性、细胞毒性或出血作用。在本综述中,我们想提请注意动物毒液及其衍生物在 DNA 损伤和/或保护免受 DNA 损伤方面的“隐藏”作用。从海绵中分离出的生物碱和萜类化合物,如avarol、ingenamine G 或 variolin B,具有结合 DNA 并产生 DNA 断裂的能力。从海鞘中分离出的 trabectidin 也能结合并损伤 DNA。从蜜蜂和黄蜂毒液中分离出的类似肽,如 mastoparan、melectin 和 melittin,也可能具有类似的作用。然而,水母、蝎子、蜘蛛和蛇的粗毒液产生的 DNA 损伤是由于细胞膜损伤和随后的氧化应激引起的,而某些动物毒液或其成分则具有遗传保护作用。目前的研究数据表明,动物毒液及其成分有可能开发出各种潜在的治疗药物;然而,在其可能的临床应用之前,应进一步研究注射途径、分子靶标、作用机制、确切剂量、可能的副作用和其他基本参数。