Department of Biology, University of Naples Federico II, 80126 Naples, Italy.
Department of Biology & CESAM, University of Aveiro, 3810-193 Aveiro, Portugal.
Sci Total Environ. 2023 Sep 20;892:164476. doi: 10.1016/j.scitotenv.2023.164476. Epub 2023 May 29.
Bioactive natural products from marine invasive species may dramatically impact native communities, while many synthetic pharmaceutical drugs are released into the marine environment and have long-lasting harmful effects on aquatic life. Sometimes, metabolites from alien species and synthetic compounds share similar mechanisms of action, suggesting comparable ecotoxicological impacts. This applies to the alkaloid caulerpin (CAU) from the green algae Caulerpa cylindracea, highly invasive in the Mediterranean Sea, and to the synthetic lipid-lowering drug fenofibrate (FFB), both acting as agonists of peroxisome proliferator-activated receptors (PPARs). Analogies with FFB, which is widely considered hazardous to the aquatic environment, have led to concerns about the ecotoxicological potential of CAU. The problem has implications for public health as CAU is well known to enter the food web accumulating in fish of commercial importance. Here, we compared the effects of FFB and CAU through biochemical and histopathological analysis on a relevant bioindicator molluscan species, the mussel Mytilus galloprovincialis. Under laboratory conditions, mussels were fed with food enriched with CAU or FFB. After treatment, biochemical markers were analyzed revealing metabolic capacity impairments, cellular damage, and changes in acetylcholinesterase activity in mussels fed with FFB-enriched food. NMR-based metabolomic studies also showed significant alterations in the metabolic profiles of FFB-treated mussels. In addition, dietary administration of FFB produced morphological alterations in the mussels' gills and digestive tubules. Obtained results confirm that FFB is harmful to aquatic life and that its release into the environment should be avoided. Conversely, dietary treatment with CAU did not produce any significant alterations in the mussels. Overall, our results pave the way for the possible valorization of the huge biomass from one of the world's worst invasive species to obtain CAU, a natural product of interest in drug discovery.
海洋入侵物种的生物活性天然产物可能对本地生物群落产生巨大影响，而许多合成药物也被排放到海洋环境中，对水生生物造成持久的有害影响。有时，外来物种的代谢物和合成化合物具有相似的作用机制，表明具有类似的生态毒性影响。这适用于绿藻石莼（Caulerpa cylindracea）中的生物碱卡鲁波宁（CAU），它在地中海地区高度入侵，以及合成降脂药物非诺贝特（FFB），两者都作为过氧化物酶体增殖物激活受体（PPARs）的激动剂。由于 FFB 被广泛认为对水生环境有害，人们对 CAU 的生态毒性潜力表示担忧。由于 CAU 众所周知会进入食物链并在具有商业重要性的鱼类中积累，因此该问题对公共健康产生影响。在这里，我们通过对相关生物标志物软体动物贻贝（Mytilus galloprovincialis）的生化和组织病理学分析，比较了 FFB 和 CAU 的作用。在实验室条件下，贻贝用富含 CAU 或 FFB 的食物喂养。处理后，分析生化标志物，发现用富含 FFB 的食物喂养的贻贝的代谢能力受损、细胞损伤和乙酰胆碱酯酶活性发生变化。基于 NMR 的代谢组学研究还表明，FFB 处理的贻贝的代谢谱发生了显著变化。此外，贻贝的鳃和消化管的饮食给药产生了形态改变。获得的结果证实，FFB 对水生生物有害，应避免将其释放到环境中。相反，CAU 的饮食处理不会对贻贝产生任何显著影响。总的来说，我们的研究结果为利用世界上最严重的入侵物种之一的巨大生物量来获得 CAU 开辟了道路，CAU 是药物发现中具有吸引力的天然产物。
