Synthesis of salicylic acid from wintergreen oil by green chemistry overcomes its cytotoxicity in keratinocyte cells and teratogenicity in zebrafish embryos.

IF 3.2 4区医学 Q1 Pharmacology, Toxicology and Pharmaceutics Toxicology Mechanisms and Methods Pub Date : 2024-02-01 Epub Date: 2024-01-29 DOI:10.1080/15376516.2023.2272184

Gökhan Özokan, Derya Cansız, Abdulkerim Bilginer, İsmail Ünal, Merih Beler, A Ata Alturfan, Ebru Emekli-Alturfan

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Abstract

Salicylic acid topical is used to treat variety of skin conditions. However, salicylic acid in these products is generated through industrial synthesis and has been shown to negatively impact fetal development and cause congenital abnormalities. We hypothesized that teratogenic effects reported in salicylic acid can be prevented by naturally synthesizing salicylic acid from wintergreen oil using green chemistry method. For this purpose, we investigated the effects of natural salicylic acid (NSA) synthesized from wintergreen oil using green chemistry and synthetic salicylic acid (SSA) on keratinocyte cell (HaCaT) proliferation and zebrafish embryo development. NSA structures were analyzed by ¹H NMR, ¹³C NMR, and GC/MS methods. Percentage inhibition against HaCaT cell was determined by MTS assay. xCelligence system was used for cellular activities. Zebrafish embryos were exposed to NSA and SSA for 72 h post-fertilization. Lipid peroxidation, nitric oxide, sialic acid, glutathione-S-transferase, catalase, and superoxide dismutase were evaluated using biochemical methods. Expressions of nqO1, gfap, bdnf, vtg, egr, cyp1a, and igf2 were determined by RT-PCR as developmental indicators. MTS and RT-cell analysis showed increased cell viability by NSA, whereas SSA decreased cell viability. NSA beneficially affected zebrafish embryo development while SSA exerted deleterious effects through oxidant-antioxidant status, inflammation, and development. Results of our study showed for the first time that synthesis of salicylic acid from wintergreen oil by green chemistry overcomes its cytotoxicity in keratinocyte cells and teratogenicity in zebrafish embryos. This finding is important for drug research on safe topical applications during pregnancy, when preventing exposure to drug and chemical-derived teratogens is vital.

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用绿色化学法从冬绿油中合成水杨酸克服了其对角质形成细胞的细胞毒性和斑马鱼胚胎的致畸性。

水杨酸外用可用于治疗各种皮肤状况。然而，这些产品中的水杨酸是通过工业合成产生的，已被证明会对胎儿发育产生负面影响，并导致先天性异常。我们假设水杨酸的致畸作用可以通过使用绿色化学方法从冬青油中天然合成水杨酸来预防。为此，我们研究了由冬青油合成的天然水杨酸（NSA）和合成水杨酸（SSA）对角质形成细胞（HaCaT）增殖和斑马鱼胚胎发育的影响。通过1H-NMR、13C-NMR和GC/MS方法分析NSA的结构。MTS法测定对HaCaT细胞的抑制率，xCelligence系统测定细胞活性。斑马鱼胚胎暴露于NSA和SSA达72 受精后数小时。采用生化方法评价脂质过氧化、一氧化氮、唾液酸、谷胱甘肽-S-转移酶、过氧化氢酶和超氧化物歧化酶。RT-PCR检测nqO1、gfap、bdnf、vtg、egr、cyp1a和igf2的表达，作为发育指标。MTS和RT细胞分析显示NSA增加了细胞活力，而SSA降低了细胞活力。NSA有益地影响斑马鱼胚胎发育，而SSA通过氧化剂抗氧化状态、炎症和发育产生有害影响。我们的研究结果首次表明，通过绿色化学从冬青油中合成水杨酸可以克服其对角质形成细胞的细胞毒性和对斑马鱼胚胎的致畸性。这一发现对妊娠期间安全局部应用的药物研究很重要，因为预防接触药物和化学衍生的致畸剂至关重要。

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来源期刊

Toxicology Mechanisms and Methods 医学-毒理学

CiteScore

6.60

自引率

3.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.