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Intermedin attenuates LPS-induced inflammation in the rat testis.

Li L, Ma P, Liu Y, Huang C, O WS, Tang F, Zhang JV - PLoS ONE (2013)

Bottom Line: In a rat model, bacterial lippolysaccharide (LPS) induced atypical orchitis, and LPS treatment upregulated the expression of IMD and one of its receptor component proteins, i.e. receptor activity modifying protein 2 (RAMP2).The restorative effect of IMD on steroidogenesis was also observed in hydrogen peroxide-treated rat primary Leydig cells culture.Our results indicate IMD plays an important protective role in spermatogenesis and steroidogenesis, suggesting therapeutic potential for IMD in pathological conditions such as orchitis.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Gene and Cell Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advance Technology, Chinese Academy of Sciences, Shenzhen City, China.

ABSTRACT
First reported as a vasoactive peptide in the cardiovascular system, intermedin (IMD), also known as adrenomedullin 2 (ADM2), is a hormone with multiple potent roles, including its antioxidant action on the pulmonary, central nervous, cardiovascular and renal systems. Though IMD may play certain roles in trophoblast cell invasion, early embryonic development and cumulus cell-oocyte interaction, the role of IMD in the male reproductive system has yet to be investigated. This paper reports our findings on the gene expression of IMD, its receptor components and its protein localization in the testes. In a rat model, bacterial lippolysaccharide (LPS) induced atypical orchitis, and LPS treatment upregulated the expression of IMD and one of its receptor component proteins, i.e. receptor activity modifying protein 2 (RAMP2). IMD decreased both plasma and testicular levels of reactive oxygen species (ROS) production, attenuated the increase in the gene expression of the proinflammatory cytokines tumor necrosis factor alpha (TNFα), interleukin 6 (IL6) and interleukin 1 beta (IL1β), rescued spermatogenesis, and prevented the decrease in plasma testosterone levels caused by LPS. The restorative effect of IMD on steroidogenesis was also observed in hydrogen peroxide-treated rat primary Leydig cells culture. Our results indicate IMD plays an important protective role in spermatogenesis and steroidogenesis, suggesting therapeutic potential for IMD in pathological conditions such as orchitis.

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IMD cotreatment suppressed the LPS-induced lipid peroxidation in rats.Lipid peroxidation was assessed by TBARS assay (MDA quantitation) in plasma and in the testis 6 h, 12 h, 72 h after LPS treatment or LPS and IMD cotreatment compared with saline control. (A) Cotreatment of IMD suppressed the LPS-induced increase in circulating lipid peroxidation levels 6 h after treatment. (B) Cotreatment of IMD suppressed the LPS-induced increase in testicular lipid peroxidation levels 6 h after treatment. All data were expressed as mean ± SEM; * P<0.05 by one-way ANOVA followed by Student–Newmann–Keuls test; n = 5–7.
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pone-0065278-g005: IMD cotreatment suppressed the LPS-induced lipid peroxidation in rats.Lipid peroxidation was assessed by TBARS assay (MDA quantitation) in plasma and in the testis 6 h, 12 h, 72 h after LPS treatment or LPS and IMD cotreatment compared with saline control. (A) Cotreatment of IMD suppressed the LPS-induced increase in circulating lipid peroxidation levels 6 h after treatment. (B) Cotreatment of IMD suppressed the LPS-induced increase in testicular lipid peroxidation levels 6 h after treatment. All data were expressed as mean ± SEM; * P<0.05 by one-way ANOVA followed by Student–Newmann–Keuls test; n = 5–7.

Mentions: Lipid peroxidation levels in plasma and testicular tissues were evaluated by TBARS assay through MDA quantification. Peroxidation of unsaturated fatty acids in membrane phospholipids is one of the multiple cytotoxic effects of oxidative stress, and lipid peroxidation is the hallmark of toxicant-induced cellular damage. LPS-treatment induced a more than 3-fold increase in plasma lipid peroxidation levels and a similar, but smaller, increase in testicular lipid peroxidation levels at 6 h after LPS treatment. Both were attenuated by IMD cotreatment (FIG.5). The lipid peroxidation levels, in both the plasma and testes, returned to basal levels at 12 h and 72 h after LPS treatment (FIG.5).


Intermedin attenuates LPS-induced inflammation in the rat testis.

Li L, Ma P, Liu Y, Huang C, O WS, Tang F, Zhang JV - PLoS ONE (2013)

IMD cotreatment suppressed the LPS-induced lipid peroxidation in rats.Lipid peroxidation was assessed by TBARS assay (MDA quantitation) in plasma and in the testis 6 h, 12 h, 72 h after LPS treatment or LPS and IMD cotreatment compared with saline control. (A) Cotreatment of IMD suppressed the LPS-induced increase in circulating lipid peroxidation levels 6 h after treatment. (B) Cotreatment of IMD suppressed the LPS-induced increase in testicular lipid peroxidation levels 6 h after treatment. All data were expressed as mean ± SEM; * P<0.05 by one-way ANOVA followed by Student–Newmann–Keuls test; n = 5–7.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3672160&req=5

pone-0065278-g005: IMD cotreatment suppressed the LPS-induced lipid peroxidation in rats.Lipid peroxidation was assessed by TBARS assay (MDA quantitation) in plasma and in the testis 6 h, 12 h, 72 h after LPS treatment or LPS and IMD cotreatment compared with saline control. (A) Cotreatment of IMD suppressed the LPS-induced increase in circulating lipid peroxidation levels 6 h after treatment. (B) Cotreatment of IMD suppressed the LPS-induced increase in testicular lipid peroxidation levels 6 h after treatment. All data were expressed as mean ± SEM; * P<0.05 by one-way ANOVA followed by Student–Newmann–Keuls test; n = 5–7.
Mentions: Lipid peroxidation levels in plasma and testicular tissues were evaluated by TBARS assay through MDA quantification. Peroxidation of unsaturated fatty acids in membrane phospholipids is one of the multiple cytotoxic effects of oxidative stress, and lipid peroxidation is the hallmark of toxicant-induced cellular damage. LPS-treatment induced a more than 3-fold increase in plasma lipid peroxidation levels and a similar, but smaller, increase in testicular lipid peroxidation levels at 6 h after LPS treatment. Both were attenuated by IMD cotreatment (FIG.5). The lipid peroxidation levels, in both the plasma and testes, returned to basal levels at 12 h and 72 h after LPS treatment (FIG.5).

Bottom Line: In a rat model, bacterial lippolysaccharide (LPS) induced atypical orchitis, and LPS treatment upregulated the expression of IMD and one of its receptor component proteins, i.e. receptor activity modifying protein 2 (RAMP2).The restorative effect of IMD on steroidogenesis was also observed in hydrogen peroxide-treated rat primary Leydig cells culture.Our results indicate IMD plays an important protective role in spermatogenesis and steroidogenesis, suggesting therapeutic potential for IMD in pathological conditions such as orchitis.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Gene and Cell Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advance Technology, Chinese Academy of Sciences, Shenzhen City, China.

ABSTRACT
First reported as a vasoactive peptide in the cardiovascular system, intermedin (IMD), also known as adrenomedullin 2 (ADM2), is a hormone with multiple potent roles, including its antioxidant action on the pulmonary, central nervous, cardiovascular and renal systems. Though IMD may play certain roles in trophoblast cell invasion, early embryonic development and cumulus cell-oocyte interaction, the role of IMD in the male reproductive system has yet to be investigated. This paper reports our findings on the gene expression of IMD, its receptor components and its protein localization in the testes. In a rat model, bacterial lippolysaccharide (LPS) induced atypical orchitis, and LPS treatment upregulated the expression of IMD and one of its receptor component proteins, i.e. receptor activity modifying protein 2 (RAMP2). IMD decreased both plasma and testicular levels of reactive oxygen species (ROS) production, attenuated the increase in the gene expression of the proinflammatory cytokines tumor necrosis factor alpha (TNFα), interleukin 6 (IL6) and interleukin 1 beta (IL1β), rescued spermatogenesis, and prevented the decrease in plasma testosterone levels caused by LPS. The restorative effect of IMD on steroidogenesis was also observed in hydrogen peroxide-treated rat primary Leydig cells culture. Our results indicate IMD plays an important protective role in spermatogenesis and steroidogenesis, suggesting therapeutic potential for IMD in pathological conditions such as orchitis.

Show MeSH
Related in: MedlinePlus