Ameliorative effects of forskolin and pinitol on ethyl methanesulfonate-induced genotoxicity in somatic and germline cells of Drosophila melanogaster.

IF 2.2 4区 医学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Tamara M Mladenović, Sanja Lj Matić
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引用次数: 0

Abstract

Forskolin and pinitol are bioactive dietary compounds studied for several pharmacological properties. Considering their widespread therapeutic application and the limited information available regarding their genotoxic and/or antigenotoxic properties, the present study investigated whether commercially available forskolin and pinitol can induce DNA damage and/or protect DNA against damage induced by ethyl methanesulfonate (EMS). The sex-linked recessive lethal (SLRL) test in germline and the alkaline comet assay in somatic cells were performed in Drosophila melanogaster to assess in vivo genotoxicity and DNA-protective effects against EMS-induced DNA damage. The SLRL assay demonstrated that neither forskolin nor pinitol induced genotoxic effects in D. melanogaster males. Both compounds significantly reduced EMS-induced sex-linked recessive lethal mutations, indicating a marked DNA-protective effect in germline cells. In the comet assay, no significant increase in DNA damage was observed following forskolin treatment, whereas pinitol induced moderate increases in the total comet score only at the highest concentration compared with the negative control, with values statistically significantly lower than those of the positive control. The greatest DNA-protective effect against EMS was observed following co-treatment with 0.5 mg/mL of forskolin or pinitol, resulting in percentage reductions of 94.2% and 80.5%, respectively. The findings suggest that forskolin and pinitol possess protective effects against EMS-induced DNA damage. Their DNA-protective capacity at non-genotoxic concentrations indicates potential chemopreventive properties and supports further investigation of their biological effects. These findings support further investigation into the molecular mechanisms underlying their protective effects and their potential application in the prevention and management of diseases associated with genomic instability.

福斯克林和蒎醇对甲基磺酸乙酯诱导的黑腹果蝇体细胞和种系细胞遗传毒性的改善作用。
福斯柯林和蒎醇是生物活性膳食化合物,研究了几种药理学性质。考虑到它们广泛的治疗应用和有限的信息,关于它们的遗传毒性和/或抗原性,本研究调查了市售的福斯克林和匹尼醇是否能诱导DNA损伤和/或保护DNA免受甲磺酸乙酯(EMS)诱导的损伤。用黑腹果蝇(Drosophila melanogaster)进行生殖系性连锁隐性致死试验(SLRL)和体细胞碱性彗星试验(alkaline comet assay),评估ems诱导DNA损伤的体内遗传毒性和DNA保护作用。SLRL试验表明,福斯克林和品尼醇均未引起雄性黑腹田鼠的遗传毒性作用。这两种化合物都能显著降低ems诱导的性别连锁隐性致死突变,表明在生殖细胞中具有显著的dna保护作用。在彗星试验中,未观察到福斯克林治疗后DNA损伤的显著增加,而匹尼醇仅在最高浓度下诱导彗星总评分适度增加,与阴性对照组相比,其值具有统计学意义上显著低于阳性对照组。与0.5 mg/mL的福斯克林或匹尼醇共同处理后,对EMS的dna保护作用最大,分别减少94.2%和80.5%。结果表明,福斯克林和品尼醇对ems诱导的DNA损伤具有保护作用。它们在非基因毒性浓度下的dna保护能力表明了潜在的化学预防特性,并支持对其生物学效应的进一步研究。这些发现支持进一步研究其保护作用的分子机制及其在预防和管理与基因组不稳定性相关的疾病方面的潜在应用。
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来源期刊
Drug and Chemical Toxicology
Drug and Chemical Toxicology 医学-毒理学
CiteScore
6.00
自引率
3.80%
发文量
99
审稿时长
3 months
期刊介绍: Drug and Chemical Toxicology publishes full-length research papers, review articles and short communications that encompass a broad spectrum of toxicological data surrounding risk assessment and harmful exposure. Manuscripts are considered according to their relevance to the journal. Topics include both descriptive and mechanics research that illustrates the risk assessment implications of exposure to toxic agents. Examples of suitable topics include toxicological studies, which are structural examinations on the effects of dose, metabolism, and statistical or mechanism-based approaches to risk assessment. New findings and methods, along with safety evaluations, are also acceptable. Special issues may be reserved to publish symposium summaries, reviews in toxicology, and overviews of the practical interpretation and application of toxicological data.
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