The effect of glutamine on Dehydroepiandrosterone-induced polycystic ovary syndrome rats

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Abstract

Background

Previous studies have shown that chronic inflammation and oxidative stress may play an important role in the pathophysiology of polycystic ovary syndrome (PCOS), and glutamine (Gln) have showed the anti-inflammatory and antioxidant properties. So the aim of this study is to investigate the effect of glutamine supplementation on PCOS rats.

Methods

Female Sprague–Dawley rats were randomly assigned into four groups ( n = 10 /group), control group, PCOS group, PCOS+ 0.5 g/kg Gln group and PCOS+ 1.0 g/kg Gln group. All the PCOS rats were administrated with 6 mg/100 g dehydroepiandrosterone (DHEA) for 20 consecutive days, all the PCOS+Gln groups were intraperitoneal injected glutamine twice in the next morning after the last DHEA injection. All the samples were collected 12 h after the last administration. Ovarian histological examinations were analyzed and the concentration of serum hormone, inflammatory and oxidative stress factors were measured.

Results

There was no obvious ovarian histological change among the PCOS group and PCOS+Gln groups. All the detected inflammation factors [C-reactive protein, interleukin (IL)-6, IL-18, tumor necrosis factor] showed significantly higher in all the PCOS groups compared to the control group ( P < 0.01), and were significantly decreased with the supplementation of 0.5 g/kg glutamine ( P < 0.01). Concentrations of superoxide dismutase were significantly lower in all the PCOS groups ( P < 0.01) compared to the control group, and increased significantly with the supplementation of 0.5 g/kg glutamine ( P < 0.01). Serum concentrations of malondialdehyde, nitric oxide synthase and nitric oxide were significantly higher in PCOS group ( P < 0.01) compared with the control group, and significantly decreased to the comparative levels of control group with supplementation of 0.5 g/kg glutamine ( P < 0.01).

Conclusion

There is low-grade inflammation and oxidative stress in DHEA-induced PCOS rats. The supplementation of 0.5 g/kg glutamine could effectively ameliorate the inflammation and oxidative stress conditions of PCOS.

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Most cited references 18

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Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis.

Mora Murri, Manuel Luque-Ramírez, María Insenser … (2013)

BACKGROUND Oxidative stress might be associated with polycystic ovary syndrome (PCOS), but relatively small studies published to date do not permit reaching a definitive conclusion. We aimed at conducting a systematic review and meta-analysis of studies evaluating circulating markers of oxidative stress in patients with PCOS. METHODS We conducted a systematic review of studies reporting circulating markers of oxidative stress in women with PCOS and controls published up to June 2012, using Entrez PubMed and EMBASE online facilities. Meta-analysis calculated standardized mean differences (SMDs) and 95% confidence intervals (95CI). RESULTS From 1633 potential studies identified electronically, 68 studies, including 4933 PCOS patients and 3671 controls, were selected. For each of nine circulating markers of oxidative stress, an individual meta-analysis was conducted. Compared with control women, patients with PCOS presented higher circulating concentrations of homocysteine (23% increase, SMD 0.6, 95CI, 0.4-0.8), malondialdehyde (47% increase, SMD 1.9, 95CI 1.2-2.6) and asymmetric dimethylarginine (36% increase, SMD 1.1, 95CI 0.6-1.6), and increased superoxide dismutase activity (34% increase, SMD 1.0, 95CI 0.5-1.4) and decreased glutathione levels (50% decrease, SMD -3.7, 95CI -6.2 to -1.2) and paraoxonase-1 activity (32% decrease, SMD -0.9, 95CI -1.3 to -0.4). Similar results were found when restricting the analyses to studies in which patients and controls were matched for age and body mass index. CONCLUSIONS Circulating markers of oxidative stress are abnormal in women with PCOS independent of weight excess. This finding suggests that oxidative stress may participate in the pathophysiology of this common disorder.

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Metabonomics reveals plasma metabolic changes and inflammatory marker in polycystic ovary syndrome patients.

Julie S. Mao, Q Hao, Xianzhong Yan … (2012)

Polycystic ovary syndrome (PCOS) is a common, clinically heterogeneous endocrine disorder affecting women of reproductive age, associated with endocrinopathy and metabolic abnormalities. Although some metabolic parameters have been investigated, very little information has been reported on the changes of small metabolites in biofluids. The aim of this study was to establish the metabolic profile of PCOS and compare it with that of controls. In this cross-sectional study of 34 women with PCOS and 36 controls, contents of small metabolites and lipids in plasma samples were measured using nuclear magnetic resonance (NMR)-based techniques and analyzed using multivariate statistical methods. Significant decrease (P < 0.05) in the levels of amino acids (leucine, isoleucine, methionine, glutamine, and arginine), citrate, choline, and glycerophosphocholine/phosphocholine (GPC/PC), and increase (P < 0.05) in the levels of lactate, dimethylamine (DMA), creatine, and N-acetyl glycoproteins were observed in PCOS patients compared with the controls. Subgroups of patients with obesity, metabolic syndrome, or hyperandrogenism exhibited greater metabolic deviations than their corresponding subgroups without these factors. PCOS patients have perturbations in amino acid metabolism, the tricarboxylic acid (TCA) cycle, and gut microflora, as well as mild disturbances in glucose and lipid metabolism. The elevated level of N-acetyl glycoproteins demonstrates the existence of low-grade chronic inflammation in PCOS patients.

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Determination of the anti-inflammatory and cytoprotective effects of l-glutamine and l-alanine, or dipeptide, supplementation in rats submitted to resistance exercise.

Philip Newsholme, Audrey Yule Coqueiro, Thaís Hypólito … (2016)

We evaluated the effects of chronic oral supplementation with l-glutamine and l-alanine in their free form or as the dipeptide l-alanyl-l-glutamine (DIP) on muscle damage, inflammation and cytoprotection, in rats submitted to progressive resistance exercise (RE). Wistar rats (n 8/group) were submitted to 8-week RE, which consisted of climbing a ladder with progressive loads. In the final 21 d before euthanasia, supplements were delivered in a 4 % solution in drinking water. Glutamine, creatine kinase (CK), lactate dehydrogenase (LDH), TNF-α, specific IL (IL-1β, IL-6 and IL-10) and monocyte chemoattractant protein-1 (MCP-1) levels were evaluated in plasma. The concentrations of glutamine, TNF-α, IL-6 and IL-10, as well as NF-κB activation, were determined in extensor digitorum longus (EDL) skeletal muscle. HSP70 level was assayed in EDL and peripheral blood mononuclear cells (PBMC). RE reduced glutamine concentration in plasma and EDL (P<0·05 v. sedentary group). However, l-glutamine supplements (l-alanine plus l-glutamine (GLN+ALA) and DIP groups) restored glutamine levels in plasma (by 40 and 58 %, respectively) and muscle (by 93 and 105 %, respectively). GLN+ALA and DIP groups also exhibited increased level of HSP70 in EDL and PBMC, consistent with the reduction of NF-κB p65 activation and cytokines in EDL. Muscle protection was also indicated by attenuation in plasma levels of CK, LDH, TNF-α and IL-1β, as well as an increase in IL-6, IL-10 and MCP-1. Our study demonstrates that chronic oral l-glutamine treatment (given with l-alanine or as dipeptide) following progressive RE induces cyprotective effects mediated by HSP70-associated responses to muscle damage and inflammation.

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Author and article information

Contributors

Gengxiang Wu: xpwugengxiang@126.com

Xue Hu: 1842767548@qq.com

Jinli Ding: 137000341@qq.com

Jing Yang: 13507182023@163.com

Journal

Journal ID (nlm-ta): J Ovarian Res

Journal ID (iso-abbrev): J Ovarian Res

Title: Journal of Ovarian Research

Publisher: BioMed Central (London )

ISSN (Electronic): 1757-2215

Publication date (Electronic): 9 May 2020

Publication date PMC-release: 9 May 2020

Publication date Collection: 2020

Volume: 13

Electronic Location Identifier: 57

Affiliations

[1 ]GRID grid.412632.0, ISNI 0000 0004 1758 2270, Reproductive Medical Centre, , Renmin Hospital of Wuhan University, ; Wuhan, 430060 Hubei Province People’s Republic of China

[2 ]Hubei Clinical Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, 430060 People’s Republic of China

[3 ]GRID grid.452849.6, ISNI 0000 0004 1764 059X, Reproductive Medical Centre, , Taihe Hospital, ; Shiyan, 442000 Hubei Province People’s Republic of China

Article

Publisher ID: 650

DOI: 10.1186/s13048-020-00650-7

PMC ID: 7211337

PubMed ID: 32386521

SO-VID: f1ddbb4e-ea24-4f13-b7ee-ca4322589d0b

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 12 February 2020

Date accepted : 15 April 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 81873817

Award ID: 81601240

Award Recipient : Gengxiang Wu

Custom metadata

ScienceOpen disciplines: Obstetrics & Gynecology

Keywords: polycystic ovary syndrome,dehydroepiandrosterone,glutamine,inflammatory factor,oxidative stress

Data availability:

ScienceOpen disciplines: Obstetrics & Gynecology

Keywords: polycystic ovary syndrome, dehydroepiandrosterone, glutamine, inflammatory factor, oxidative stress

The effect of glutamine on Dehydroepiandrosterone-induced polycystic ovary syndrome rats

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Most cited references 18

Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis.

Metabonomics reveals plasma metabolic changes and inflammatory marker in polycystic ovary syndrome patients.

Determination of the anti-inflammatory and cytoprotective effects of l-glutamine and l-alanine, or dipeptide, supplementation in rats submitted to resistance exercise.

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