Evidence-based hormonal, mutational, and endocrine-disrupting chemical-induced zebrafish as an alternative model to study PCOS condition similar to mammalian PCOS model

Sudhakaran, Gokul; Guru, Ajay; Muthu, B. Hari Deva; Murugan, Raghul; Arshad, Aziz; Arockiaraj, Jesu

doi:10.1016/j.lfs.2021.120276

Cited by 28 publications

(12 citation statements)

References 123 publications

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“…. It affects up to 20% of women of reproductive age, making it the most common endocrine disease among premenopausal women (Sudhakaran, Guru, Deva, Murugan, Arshad, & Arockiaraj, 2022). The key diagnostic features are hyperandrogenism, menstrual irregularities (oligo/anovulation) and polycystic ovarian morphology on an ultrasound scan.…”

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confidence: 99%

Nimbin analog N2 alleviates high testosterone induced oxidative stress in CHO cells and alters the expression of Tox3 and Dennd1a signal transduction pathway involved in the PCOS zebrafish

Sudhakaran

Rajesh

Murugan

et al. 2022

Phytotherapy Research

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Polycystic ovarian syndrome (PCOS) is a hormonal disorder that causes enlargement of ovaries and follicular maturation arrest, which lacks efficient treatment. N2, a semi-natural triterpenoid from the neem family, was already reported to have antioxidant and antiinflammatory properties in our previous report. This study investigated the anti-androgenic property of N2 on testosterone-induced oxidative stress in Chinese Hamster Ovarian cells (CHO) and PCOS zebrafish model. The testosterone exposure disrupted the antioxidant enzymes and ROS level and enhanced the apoptosis in both CHO cells and PCOS zebrafish. However, N2 significantly protected the CHO cells from ROS and apoptosis. N2 improved the Gonado somatic index (GSI) and upregulated the expression of the SOD enzyme in zebrafish ovaries. Moreover, the testosterone-induced follicular maturation arrest was normalized by N2 treatment in histopathology studies. In addition, the gene expression studies of Tox3 and Denndla in zebrafish demonstrated that N2 could impair PCOS condition. Furthermore, to confirm the N2 activity, the in-silico studies were performed against PCOS susceptible genes Tox3 and Dennd1a using molecular docking and molecular dynamic simulations. The results suggested that N2 alleviated the oxidative stress and apoptosis in-vitro and in-vivo and altered the expression of PCOS key genes.

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confidence: 99%

Nimbin analog N2 alleviates high testosterone induced oxidative stress in CHO cells and alters the expression of Tox3 and Dennd1a signal transduction pathway involved in the PCOS zebrafish

Sudhakaran

Rajesh

Murugan

et al. 2022

Phytotherapy Research

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“…Data of current study showed no significant difference between the levels of FSH, LH, prolactin and Estradiol measured in the menstruation day 2-3 of ovulation induction. FSH stimulates the development of ovarian follicles in granulosa cells, whereas LH action is involved in follicle development and maturation (Sudhakaran et al,2022) Endometrial thickness has been explored as a predictor of pregnancy outcome (Al-Dujaily and Aburgheef, 2012). It has been recorded that, with increasing endometrium thickness, up to 14 mm, the pregnancy rates will decline.…”

Section: Discussionmentioning

confidence: 99%

Study the effect of piroxicam treatment for intrauterine insemination using density gradient for sperm preparation

Naser

Al-Dujaily

Al-Anbari

2022

ijhs

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Back ground: Endometrium contraction following intra-uterine insemination(IUI) was considered one of implantation failure causes.Aim of the study: The primary purpose of the study was to ascertain the effect of piroxicam treatment on pregnancy outcome following six days of intrauterine insemination. Materials and Methods: The study was accomplished in the High Institute for Infertility Diagnosis and Assisted Reproductive Technologies, Al-Nahrain University through the period from Nov. 2020 till Oct. 2021 .Forty infertile couples were selected randomly for IUI and divided into 20 couple treated with piroxicam and other 20 couples were not treated with piroxicam. The semen samples were prepared by discontinuous density gradient. Results: There was no significant differences regarding mean FSH level (p=0.769), LH level(p=0.79) prolactin level (p=0.299), E2 level (p=0.348) and TSH level (p=0.950)between the studied groups. There was no significant difference in dominant follicles counts, follicular sizes or endothelial thickness between the two groups. The results showed a significant improvement in sperm motility and morphology (p < 0.05) after in vitro activation by density gradient technique compared to before activation. In the piroxicam group ,4 out of 20 women became pregnant while in non-piroxicam group ,3 spouses were pregnant 15%when density gradient activation technique was used.

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“…The solvent peak (CDCl 3 = 77. 16) is used as the internal standard for 13 C-NMR data. On a Bruker Impact HD mass spectrometer, high-resolution mass spectral analysis (HRMS) was conducted.…”

Section: Nmr and Hrmsmentioning

confidence: 99%

“…[15] These larvae have transparent bodies for several days after fertilization, allowing researchers to examine the living organs such as the heart, liver, and pancreas. [16] Drug toxicity and treatment studies on zebrafish larvae can be performed to analyze the developmental toxicity, apoptosis, and repair the condition in the liver. [17][18][19] These advantages motivated us to inves-tigate anti-inflammatory and antioxidant properties of compound 1 in HepG2 cells and zebrafish larvae model.…”

Section: Introductionmentioning

confidence: 99%

“…To defend against oxidative stress and inflammation, zebrafish have the same mechanisms as mammals [15] . These larvae have transparent bodies for several days after fertilization, allowing researchers to examine the living organs such as the heart, liver, and pancreas [16] . Drug toxicity and treatment studies on zebrafish larvae can be performed to analyze the developmental toxicity, apoptosis, and repair the condition in the liver [17–19] .…”

Section: Introductionmentioning

confidence: 99%

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6‐Gingerdione Reduces Apoptotic Conditions in HepG2 Cells and Inhibits Inflammatory Cytokine Gene Expression in Alcoholic Liver Injured Zebrafish Larvae

Guru

Manjunathan

Sudhakaran

et al. 2022

Chemistry & Biodiversity

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Antioxidant natural products and their analogs especially phenolic compounds, exhibit diverse biological properties, including anti‐inflammatory, antioxidant, and anticancer activities. Ginger which is widely used worldwide for various beneficial effects also contains several phenolic antioxidants, and 6‐gingerol is one of the natural products studied extensively. However, the molecular mechanism of synthetically synthesized 6‐gingerdione (compound 1) from 6‐gingerol was not known. In this study, compound 1 and methylated 6‐gingerdione (compound 2) were obtained semi synthetically from 6‐gingerol. Compound 1 and 2 are subjected to SwissADME prediction. Then the protective effect of compound 1 was analyzed in 2 % EtOH induced HepG2 cells and zebrafish larvae. Hydroxyl and nitric oxide scavenging assays reveal that compound 1 showed more antioxidant activity than compound 2 at 50 μM. Moreover, compound 1 exhibited good anti‐inflammatory activity via lipoxygenase inhibition and proteinase inhibition. Apoptosis and oxidative stress in HepG2 cells were induced by 2 % EtOH and treated with compound 1. Compound 1 significantly inhibited the EtOH induced nitric oxide production, apoptosis, and ROS generation in HepG2 cells. Encouraged by the in‐vitro antioxidant and anti‐inflammatory activities, compound 1 was then investigated for its protective effect in 2 % EtOH induced ALD zebrafish larva. Compound 1 protected the zebrafish larvae from liver injury by suppressing inflammatory (COX‐2, TNF‐α, and IL‐1β) and lipogenic genes (C/EBP‐α, SREBP1, and IL‐1β) while upregulating the antioxidant gene. Our findings indicate that compound 1 synthesized from 6‐gingerol ameliorated liver injury that likely, contributes to its potential antioxidant and anti‐inflammatory properties.

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Evidence-based hormonal, mutational, and endocrine-disrupting chemical-induced zebrafish as an alternative model to study PCOS condition similar to mammalian PCOS model

Cited by 28 publications

References 123 publications

Nimbin analog N2 alleviates high testosterone induced oxidative stress in CHO cells and alters the expression of Tox3 and Dennd1a signal transduction pathway involved in the PCOS zebrafish

Nimbin analog N2 alleviates high testosterone induced oxidative stress in CHO cells and alters the expression of Tox3 and Dennd1a signal transduction pathway involved in the PCOS zebrafish

Study the effect of piroxicam treatment for intrauterine insemination using density gradient for sperm preparation

6‐Gingerdione Reduces Apoptotic Conditions in HepG2 Cells and Inhibits Inflammatory Cytokine Gene Expression in Alcoholic Liver Injured Zebrafish Larvae

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