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新兴污染物三氯生引发重要商业鱼类印度鯝(Labeo catla)的内分泌紊乱、生殖损伤和氧化应激:通过分子、组织病理学和生物信息学方法的深入研究

Emerging contaminant triclosan incites endocrine disruption, reproductive impairments and oxidative stress in the commercially important carp, Catla (Labeo catla): An insight through molecular, histopathological and bioinformatic approach.

作者信息

Adhikari Anupam, Das Basanta Kumar, Ganguly Satabdi, Nag Subir Kumar, Sadhukhan Debalina, Raut Subhashree Subhasmita

机构信息

ICAR- Central Inland Fisheries Research Institute, Barrackpore, Kolkata 700120, India.

ICAR- Central Inland Fisheries Research Institute, Barrackpore, Kolkata 700120, India.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2023 Jun;268:109605. doi: 10.1016/j.cbpc.2023.109605. Epub 2023 Mar 10.

Abstract

Triclosan (TCS), a broad-spectrum antimicrobial agent is ubiquitous in aquatic ecosystems; however, the mechanisms regarding TCS-induced reproductive toxicity in the teleost still remains uncertain. In this context, Labeo catla were subjected to sub-lethal doses of TCS for 30 days and variations in expression of genes and hormones comprising the hypothalamic-pituitary-gonadal (HPG) axis along with alterations in sex steroids were evaluated. Moreover, manifestation of oxidative stress, histopathological alterations, in silico docking and the potential to bioaccumulate were also investigated. Exposure to TCS may lead to an inevitable onset of the steroidogenic pathway through its interaction at several loci along the reproductive axis: TCS stimulated synthesis of kisspeptin 2 (Kiss 2) mRNAs which in turn prompts the hypothalamus to secrete gonadotropin-releasing hormone (GnRH), resulting in elevated serum 17β-estradiol (E) as a consequence; TCS exposure increased aromatase synthesis by brain, which by converting androgens to oestrogens may raise E levels; Moreover, TCS treatment resulted in elevated production of GnRH and gonadotropins by the hypothalamus and pituitary, respectively resulting in the induction of E. The elevation in serum E may be linked to abnormally elevated levels of vitellogenin (Vtg) with harmful consequences evident as hypertrophy of hepatocytes and increment in hepatosomatic indices. Additionally, molecular docking studies revealed potential interactions with multiple targets viz. Vtg and luteinizing hormone (LH). Furthermore, TCS exposure induced oxidative stress and caused extensive damage to tissue architecture. This study elucidated molecular mechanisms underlying TCS-induced reproductive toxicity and the need for regulated use and efficient alternatives which could suffice for TCS.

摘要

三氯生(TCS)是一种广谱抗菌剂,在水生生态系统中普遍存在;然而,关于TCS对硬骨鱼生殖毒性的机制仍不确定。在此背景下,对印度野鲮施加亚致死剂量的TCS持续30天,并评估了包括下丘脑-垂体-性腺(HPG)轴在内的基因和激素表达变化以及性类固醇的改变。此外,还研究了氧化应激的表现、组织病理学改变、分子对接以及生物累积潜力。接触TCS可能通过其在生殖轴多个位点的相互作用导致类固醇生成途径不可避免地启动:TCS刺激了亲吻素2(Kiss 2)mRNA的合成,进而促使下丘脑分泌促性腺激素释放激素(GnRH),结果导致血清17β-雌二醇(E)升高;接触TCS增加了大脑中芳香化酶的合成,通过将雄激素转化为雌激素可能提高E水平;此外,TCS处理分别导致下丘脑和垂体中GnRH和促性腺激素的产生增加,从而诱导E的产生。血清E的升高可能与卵黄蛋白原(Vtg)水平异常升高有关,有害后果表现为肝细胞肥大和肝体指数增加。此外,分子对接研究揭示了与多个靶点即Vtg和促黄体生成素(LH)的潜在相互作用。此外,接触TCS会诱导氧化应激并对组织结构造成广泛损害。本研究阐明了TCS诱导生殖毒性的分子机制以及对TCS进行规范使用和寻找有效替代品的必要性。

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