Effect of gender differences on the regulation of renal ischemia‑reperfusion‑induced inflammation in mice

Kang,Kyung Pyo; Lee,Jung Eun; Lee,Ae Sin; Jung,Yu Jin; Kim,Dal; Lee,Sik; Hwang,Hong Pil; Kim,Won; Park,Sung Kwang

doi:10.3892/mmr.2014.2089

June-2014 Volume 9 Issue 6

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June-2014 Volume 9 Issue 6

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Article Open Access

Effect of gender differences on the regulation of renal ischemia‑reperfusion‑induced inflammation in mice

Authors:
- Kyung Pyo Kang
- Jung Eun Lee
- Ae Sin Lee
- Yu Jin Jung
- Dal Kim
- Sik Lee
- Hong Pil Hwang
- Won Kim
- Sung Kwang Park
View Affiliations / Copyright

Affiliations: Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju‑si, Jeollabuk‑do 561‑712, Republic of Korea, Department of Surgery, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju‑si, Jeollabuk‑do 561‑712, Republic of Korea

Copyright: © Kang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
Pages: 2061-2068
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Published online on: March 28, 2014

https://doi.org/10.3892/mmr.2014.2089
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Abstract

Inflammation is a key mediator of renal ischemia‑reperfusion (IR) injury. Gender disparities have been reported in acute and chronic kidney disease. In particular, males are considered to be more susceptible to renal ischemic injury compared with females according to animal studies. The purpose of the present study was to investigate the effect of gender on the renal inflammatory response following acute renal IR injury in mice. Experiments were performed in male and female C57BL/6 mice. Two weeks prior to the study, castration or ovariectomy were performed and testosterone propionate (100 µg/kg) or 17β‑estradiol (100 µg/kg) was injected. Acute kidney injury (AKI) was induced by bilateral clamping of the renal pedicle for 23 min. Histological examination, western blot analysis and quantitative polymerase chain reaction were performed. In the acute renal IR injury model, the female mice were more resistant to kidney injury compared with the male mice. However, castration of the male mice reduced the levels of IR‑induced tubular injury and macrophage infiltration compared with those in the injured male mice. Supplementation of testosterone reversed this protective effect in the male AKI model. Depletion of estrogen in the female mice increased the levels of IR‑induced tubular injury and macrophage infiltration compared with those in the injured female mice. However, supplementation of estrogen in the ovariectomized female mice attenuated the IR‑induced tubular injury and reduced the levels of macrophage infiltration. The expression levels of inflammatory cytokines, including tumor necrosis factor‑α, monocyte chemotactic protein‑1, interferon‑γ and chemokine (C‑C motif) ligand 17, were elevated in the male AKI mice compared with those in the control male mice, and were attenuated by castration. Estrogen depletion in the female mice significantly increased the expression levels of the renal inflammatory cytokines compared with those in the injured female mice, and were attenuated by estrogen supplementation in the ovariectomized female mice. These results suggested that the male gender confers greater susceptibility to IR renal injury due to an enhanced inflammatory response.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Effect of gender differences on the regulation of renal ischemia‑reperfusion‑induced inflammation in mice

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