Dataset Information

Effects of the Essential Oil from Pistacia lentiscus Var. chia on the Lateral Line System and the Gene Expression Profile of Zebrafish (Danio rerio).

ABSTRACT: Mastic essential oil exhibits anti-bacterial, anti-inflammatory, and anti-oxidant properties. With the growing interest of the use of mastic oil in the food and pharmaceutical industry, systematic in vivo studies are needed to address controlled usage and safety issues. In the present work we evaluated the safety of mastic oil using as a model the zebrafish lateral line system. In addition, we studied the gene expression profile of zebrafish fed with mastic oil-supplemented diet using microarray analysis. Our results showed that the hair cells of lateral line neuromasts are functional upon exposure of zebrafish larvae up to 20 ppm of mastic essential oil, while treatment with higher concentrations, 100 and 200 ppm, resulted in increased larvae mortality. Dietary supplementation of zebrafish with mastic essential oil led to differential expression of interferon response-related genes as well as the immune responsive gene 1 (irg1) that links cellular metabolism with immune defense. Notably, mucin 5.2, a constituent of the mucus hydrogel that protects the host against invading pathogens, was up-regulated. Our in vivo work provides information concerning the safety of mastic essential oil use and suggests dietary effects on gene expression related with the physical and immunochemical properties of the gastrointestinal system.

SUBMITTER: Serifi I

PROVIDER: S-EPMC6864543 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Effects of the Essential Oil from Pistacia lentiscus Var. chia on the Lateral Line System and the Gene Expression Profile of Zebrafish (Danio rerio).

Serifi Iliana I Tzima Eleni E Bardouki Haido H Lampri Evangeli E Papamarcaki Thomais T

Molecules (Basel, Switzerland) 20191030 21

Mastic essential oil exhibits anti-bacterial, anti-inflammatory, and anti-oxidant properties. With the growing interest of the use of mastic oil in the food and pharmaceutical industry, systematic in vivo studies are needed to address controlled usage and safety issues. In the present work we evaluated the safety of mastic oil using as a model the zebrafish lateral line system. In addition, we studied the gene expression profile of zebrafish fed with mastic oil-supplemented diet using microarray ...[more]

PMID: 31671694

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Project description:Hypertension poses a significant global health burden and is closely associated with cardiovascular morbidity. Pistacia lentiscus var. chia, commonly known as mastic, has emerged as a potential nutraceutical, due to its diverse pharmacological properties, including antioxidant and vasodilatory effects. Yet, its impact on hypertension in translational in vivo models and on hypertension-associated abnormalities in circulation, vasculature and kidneys have not been investigated. Herein we sought to decipher the putative antihypertensive potential of mastic, focusing on vascular and renal endothelium in clinically relevant in vivo models of essential hypertension. Two translational in vivo models of hypertension induced by Angiotensin II and Deoxycorticosterone acetate (DOCA)-High Salt in male rats, were utilized. Mastic administration at a therapeutic dose (220mg/kg, per os) was administered daily for four weeks, after the establishment of hypertension. Non-invasive blood pressure measurements and whole blood RNA sequencing and metabolomics were performed. Real-time PCR and Western blot analysis were conducted in kidney and aorta, to decipher its underlying antihypertensive mechanism. Mastic administration significantly reduced systolic, diastolic, and mean blood pressure in both in vivo hypertensive models. RNA sequencing revealed distinct gene expression profiles, with modulation of immune-related pathways in the Angiotensin II model and metabolic pathways in the DOCA-HS model. Additionally, RNA sequencing analysis revealed that mastic downregulated Rhob, Jun, Txnip and Egr1 mRNA expression in the circulation, paving towards a putative antioxidant and endothelial-targeted mechanism. Metabolomic analysis identified lysophosphatidylinositol upregulation as a consistent effect of mastic in both in vivo models, being implicated with improved endothelial homeostasis. RT-PCR analysis in the kidneys and aorta, showed that mastic increased endothelial markers such as Vegfa and Egr-1 mRNA expression in both experimental models. Concerning the endothelial homeostasis, mastic additionally increased renal nitric oxide synthase phosphorylation in both in vivo models of hypertension. This study highlights the potential of mastic as a natural adjuvant therapy for hypertension. The findings shed new light on its molecular mechanisms of action, providing insights into its protective impact on renal endothelium.

Project description:Hereditary sensory and autonomic neuropathy type 2 (HSNAII) is a rare pathology characterized by an early onset of severe sensory loss (all modalities) in the distal limbs. It is due to autosomal recessive mutations confined to exon "HSN2" of the WNK1 (with-no-lysine protein kinase 1) serine-threonine kinase. While this kinase is well studied in the kidneys, little is known about its role in the nervous system. We hypothesized that the truncating mutations present in the neural-specific HSN2 exon lead to a loss-of-function of the WNK1 kinase, impairing development of the peripheral sensory system. To investigate the mechanisms by which the loss of WNK1/HSN2 isoform function causes HSANII, we used the embryonic zebrafish model and observed strong expression of WNK1/HSN2 in neuromasts of the peripheral lateral line (PLL) system by immunohistochemistry. Knocking down wnk1/hsn2 in embryos using antisense morpholino oligonucleotides led to improper PLL development. We then investigated the reported interaction between the WNK1 kinase and neuronal potassium chloride cotransporter KCC2, as this transporter is a target of WNK1 phosphorylation. In situ hybridization revealed kcc2 expression in mature neuromasts of the PLL and semi-quantitative RT-PCR of wnk1/hsn2 knockdown embryos showed an increased expression of kcc2 mRNA. Furthermore, overexpression of human KCC2 mRNA in embryos replicated the wnk1/hsn2 knockdown phenotype. We validated these results by obtaining double knockdown embryos, both for wnk1/hsn2 and kcc2, which alleviated the PLL defects. Interestingly, overexpression of inactive mutant KCC2-C568A, which does not extrude ions, allowed a phenocopy of the PLL defects. These results suggest a pathway in which WNK1/HSN2 interacts with KCC2, producing a novel regulation of its transcription independent of KCC2's activation, where a loss-of-function mutation in WNK1 induces an overexpression of KCC2 and hinders proper peripheral sensory nerve development, a hallmark of HSANII.

Dataset Information

Effects of the Essential Oil from Pistacia lentiscus Var. chia on the Lateral Line System and the Gene Expression Profile of Zebrafish (Danio rerio).

Publications

Effects of the Essential Oil from <i>Pistacia lentiscus</i> Var. <i>chia</i> on the Lateral Line System and the Gene Expression Profile of Zebrafish (<i>Danio rerio</i>).

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