scholarly journals The Protective Effect of Echinochrome A on Extracellular Matrix of Vocal Folds in Ovariectomized Rats

Marine Drugs ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 77
Author(s):  
Ji Min Kim ◽  
Jeong Hun Kim ◽  
Sung-Chan Shin ◽  
Gi Cheol Park ◽  
Hyung Sik Kim ◽  
...  

Here, we investigated the effects of sex hormones on extracellular matrix (ECM)-related gene expression in the vocal fold lamina propria of ovariectomized (after ovary removal) rats and verified whether echinochrome A (ECH) exerts any therapeutic effects on ECM reconstitution after estrogen deficiency in ovariectomized rats. Sprague–Dawley female rats (9 weeks old) were acclimatized for a week and randomly divided into three groups (n = 15 each group) as follows: group I (sham-operated rats, SHAM), group II (ovariectomized rats, OVX), group III (ovariectomized rats treated with ECH, OVX + ECH). Rats from the OVX + ECH group were intraperitoneally injected with ECH at 10 mg/kg thrice a week after surgery for 6 weeks. And rats were sacrificed 6 weeks after ovariectomy. Estradiol levels decreased in OVX group compared with the SHAM group. ECH treatment had no effect on the levels of estradiol and expression of estrogen receptor β (ERβ). The evaluation of ECM components showed no significant changes in elastin and hyaluronic acid levels between the different groups. Collagen I and III levels were lower in OVX group than in SHAM group but increased in OVX + ECH group. The mRNA levels of matrix metalloproteinase (MMP)-1, -2, -8, and -9 were significantly higher in the OVX group than in the SHAM group, but decreased in the OVX + ECH group. Thus, changes were observed in ECM-related genes in the OVX group upon estradiol deficiency that were ameliorated by ECH administration. Thus, the vocal fold is an estradiol-sensitive target organ and ECH may have protective effects on the ECM of vocal folds in ovariectomized rats.

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Fei Ge ◽  
Haoran Yang ◽  
Weiting Lu ◽  
Huilian Shi ◽  
Qinlei Chen ◽  
...  

Perimenopausal women are associated with increased risks of depression and anxiety, which may be potentially related to the lack of ovarian hormone with antidepression activity in the body. However, the precise mechanism remains unclear so far. This study first adopted the Sprague-Dawley (SD) female rats to construct the ovariectomy (OVX) combined with a chronic unpredictable stress (CUS) model. Then, a series of behavioral experimental results revealed that the ovariectomized rats receiving CUS had remarkably elevated anxiety and depression behaviors relative to those in sham group rats, and the sucrose preference rate in the sucrose preference test (SPT) was evidently reduced. In elevated plus maze test (EPM) experiment, the open arm entry time and open arm duration were decreased. In the open field test (OFT), the number of line crossings, rearing number, center square entries, and center square duration were reduced; the grooming time was extended; and the number of fecal particles in rats was increased. In the forced swimming test (FST), the rat immobility rate was increased, while the numbers of swimming and crawling were decreased. Afterwards, we discovered that OVX downregulated the serum levels of estradiol and corticosterone in rats. Thereafter, IF results suggested that OVX dramatically induced the increasing of the number of activated microglial cells in prefrontal cortices and the level of M1-type marker iNOS. Finally, PCR results demonstrated that, compared with the sham group, the proinflammatory and prooxidative genes, such as IL-1β, IL-6, TNF-α, iNOS, and CX3CR1, were upregulated in the prefrontal cortices of OVX rats after CUS stimulation, whereas the anti-inflammatory factor Arg1 and microglial cell negative regulatory factor CD200 were downregulated. To sum up, OVX enhances the CUS-mediated anxiety and depression phenomena in rats, and its mechanism may be related to inducing the activation and polarization of microglial cells in the prefrontal cortex of animal and to accelerating the inflammatory response.


2015 ◽  
Vol 73 (2) ◽  
pp. 132-139 ◽  
Author(s):  
Hamid Azizi-Malekabadi ◽  
Masoume Pourganji ◽  
Hoda Zabihi ◽  
Mohsen Saeedjalali ◽  
Mahmoud Hosseini

The effects of tamoxifen (TAM) on anxiety and depression-like behavior in ovariectomized (OVX) and naïve female rats were investigated. The animals were divided into Sham-TAM, OVX-TAM, Sham and OVX groups. Tamoxifen (1 mg/kg) was administered for 4 weeks. In the forced swimming test, the immobility times in the OVX and Sham-TAM groups were higher than in the Sham group. In the open field, the numbers of central crossings in the OVX and Sham-TAM groups were lower than the number in the Sham group, and the number of peripheral crossings in the OVX group was lower than the number in the Sham group. In the elevated plus maze, the numbers of entries to the open arm among the animals in the Sham-TAM and OVX groups were lower than the number in the Sham group, while the number of entries to the open arm in the OVX-TAM group was higher than the number in the OVX group. It was shown that deletion of ovarian hormones induced anxiety and depression-like behavior. Administration of tamoxifen in naïve rats led to anxiety and depression-like behavior that was comparable with the effects of ovarian hormone deletion. It can be suggested that tamoxifen antagonizes the effects of ovarian hormones. It also seems that tamoxifen has anxiolytic effects on ovariectomized rats.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Zhiguo Zhang ◽  
Jiazi Dong ◽  
Meijie Liu ◽  
Yan Li ◽  
Jinghua Pan ◽  
...  

The aim of this study was to evaluate effects of aqueous extract fromCortex acanthopanacis(CAE) on osteoporosis rats induced by ovariectomy (OVX) using aqueous extract fromFolium Epimedii(FEE) as positive control agent. Three-month-old female rats that underwent OVX were treated with CAE. After 12 weeks, bone mineral density (BMD) and indices of bone histomorphometry of tibia were measured. Levels of protein and mRNA expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) in tibia were evaluated. In addition, the serum concentrations of osteocalcin (OC), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), calcitonin (CT), and parathyroid hormone (PTH) were determined. Administration of CAE significantly prevented OVX-induced rats from gain of the body weight. Treatment with CAE increased bone mass remarkably and showed a significant inhibitory effect on bone resorption by downregulating significantly the expression of RANKL in tibia of OVX rats. Meanwhile, treatment of CAE significantly reduced serum level of IL-1βand increased level of CT in OVX rats. This suggests that CAE has the potential to be used as an alternative therapeutic agent for postmenopausal osteoporosis.


2009 ◽  
Vol 41 (8) ◽  
pp. 585-594 ◽  
Author(s):  
Ya Lin ◽  
Masaru Yamashita ◽  
Jingxian Zhang ◽  
Changying Ling ◽  
Nathan V. Welham

2005 ◽  
Vol 114 (9) ◽  
pp. 662-670 ◽  
Author(s):  
Jennifer K. Hansen ◽  
Susan L. Thibeault ◽  
Jennifer F. Walsh ◽  
Xiao Zheng Shu ◽  
Glenn D. Prestwich

Objectives: A prospective, controlled animal study was performed to determine whether the use of injectable, chemically modified hyaluronic acid (HA) derivatives at the time of intentional vocal fold resection might facilitate wound repair and preserve the unique viscoelastic properties of the vocal fold extracellular matrix. Methods: We performed bilateral vocal fold biopsies on 33 rabbits. Two groups of rabbits were unilaterally treated with 2 different HA derivatives — Carbylan-SX and HA-DTPH-PEGDA — at the time of resection. Saline was injected as a control into the contralateral fold. The animals were painlessly sacrificed 3 weeks after biopsy and injection. The outcomes measured included histologic fibrosis level, tissue HA level, and tissue viscosity and elasticity. Results: The Carbylan-SX—treated vocal folds were found to have significantly less fibrosis than the saline-treated controls. The levels of HA in the treated vocal folds were not significantly different from those in the controls at 3 weeks as measured by enzyme-linked immunosorbent assay. The Carbylan-SX—treated vocal folds had significantly improved biomechanical properties of elasticity and viscosity. The HA-DTPH-PEGDA injections yielded significantly improved viscosity, but not elasticity. Conclusions: Prophylactic in vivo manipulation of the extracellular matrix with an injectable Carbylan-SX hydrogel appears to induce vocal fold tissue regeneration to yield optimal tissue composition and biomechanical properties favorable for phonation.


Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 735
Author(s):  
Magdalena Grill ◽  
Isaac Lazzeri ◽  
Andrijana Kirsch ◽  
Nina Steurer ◽  
Tanja Grossmann ◽  
...  

The voice disorder Reinke’s edema (RE) is a smoking- and voice-abuse associated benign lesion of the vocal folds, defined by an edema of the Reinke’s space, accompanied by pathological microvasculature changes and immune cell infiltration. Vocal fold fibroblasts (VFF) are the main cell type of the lamina propria and play a key role in the disease progression. Current therapy is restricted to symptomatic treatment. Hence, there is an urgent need for a better understanding of the molecular causes of the disease. In the present study, we investigated differential expression profiles of RE and control VFF by means of RNA sequencing. In addition, fast gene set enrichment analysis (FGSEA) was performed in order to obtain involved biological processes, mRNA and protein levels of targets of interest were further evaluated. We identified 74 differentially regulated genes in total, 19 of which were upregulated and 55 downregulated. Differential expression analysis and FGSEA revealed upregulated genes and pathways involved in extracellular matrix (ECM) remodeling, inflammation and fibrosis. Downregulated genes and pathways were involved in ECM degradation, cell cycle control and proliferation. The current study addressed for the first time a direct comparison of VFF from RE to control and evaluated immediate functional consequences.


2020 ◽  
Author(s):  
Congqing Li ◽  
Lin Cong ◽  
Youjiang Xu ◽  
Wenyan Wang

Abstract Background: Intrauterine adhesions will affect the amount of menstrual and fertility, endometrial fibrosis is the last manifestation of the IUA. MMP-9 is closely related to fibrosis. The purpose of the study was to assess the role of MMP-9 in intrauterine adhesion (IUA) rats and patients.Methods:40 female rats and 24 patients were enrolled in this study. We used immunohistochemistry to detect the MMP-9 expression in rats and human endometrial tissues, as well as detected their protein levels with western blot. In addition, we detected their mRNA expression levels with qRT-PCR.Results: The expression of MMP-9 in the IUA rats was reduced compared with the Sham group and Ctrl group (P< 0.05), and the expression of MMP-9 was also reduced in the IUA patients compared with the Ctrl group (P< 0.05). The mRNA levels of MMP-9 in endometrium were presenting similar results (P< 0.05). Conclusions: Our study suggests that MMP-9 may play an important role in fibrosis of the IUA. It may provide a new reference for the treatment of IUA in the future.


2007 ◽  
Vol 116 (10) ◽  
pp. 762-769 ◽  
Author(s):  
Tsunehisa Ohno ◽  
Shigeru Hirano ◽  
Shin-Ichi Kanemaru ◽  
Masaru Yamashita ◽  
Hiroo Umeda ◽  
...  

Objectives: Vocal fold scarring remains a therapeutic challenge. Previous studies have indicated that hepatocyte growth factor (HGF), a strong antifibrotic element, has therapeutic potential for restoring scarred vocal folds. To enhance the effect of HGF in vivo, we developed a novel drug delivery system (DDS) in which HGF is embedded in gelatin hydrogel and continuously released over a period of 2 weeks. In the present study we investigated the therapeutic efficacy of the HGF DDS on vocal fold scarring by using a canine model. Methods: The vocal folds of 8 beagles were unilaterally scarred by stripping the entire layer of the lamina propria. The contralateral vocal folds were kept intact as normal controls. One month after the procedure, hydrogels (0.5 mL) containing 1 μg of HGF were injected into the scarred vocal folds of 4 dogs (HGF-treated group), whereas hydrogels containing saline solution were injected in the other 4 dogs (sham group). Histologic and vibratory examinations were completed for each group 6 months after the initial surgery. Results: The excised larynx experiments showed significantly better vibration in terms of mucosal wave amplitude and glottal closure in the HGF-treated group compared to the sham group. Histologic evaluation of the vocal folds indicated remarkable reduction in collagen deposition and tissue contraction, with favorable restoration of hyaluronic acid and elastin in the HGF-treated group. Conclusions: The present findings suggest that the novel HGF DDS may provide favorable effects in restoring the vibratory properties of scarred vocal folds.


2020 ◽  
Vol 48 (11) ◽  
pp. 030006052096580
Author(s):  
Hai-Bo Zou ◽  
Xiao-Feng Sun

Objective To investigate the mechanism by which curcumin prevents lung injury in a rat model of limb ischaemia-reperfusion injury. Methods Rats were randomized into four groups ( n = 20): control group (sham group); ischaemia-reperfusion group (I/R group); curcumin group (I/R+Cur group); and inhibitor of agomir-21 group (I/R+Cur+antagomir-21 group). At 3 h after reperfusion, lung tissues were collected for histopathology and immunohistochemistry to determine the apoptosis index (AI). Lung injury score (LIS) and lung wet/dry (W/D) ratio were determined. Lung microRNA-21 (miR-21) mRNA levels were measured using reverse transcription–polymerase chain reaction. Toll-like receptor 4 (TLR4) and nuclear factor kappa-B p65 (NF-κB p65) protein levels were measured by Western blot analysis. Tumour necrosis factor (TNF)-α and interleukin (IL)-1β levels were determined by enzyme-linked immunosorbent assays. Results In the I/R group, the W/D, LIS, AI, miR-21 mRNA, TLR4, NF-κB p65, TNF-α and IL-1β were significantly increased and the PaO2 was decreased compared with the sham group. Evidence of lung injury was observed in the I/R group and this was alleviated in the I/R+Cur group. An inhibitor of miR-21 (antagomir-21) reversed the protective effects of curcumin. Conclusion Curcumin post-treatment can alleviate the lung injuries induced by limb ischaemia-reperfusion via downregulating the levels of miR-21 mRNA.


1990 ◽  
Vol 4 (2) ◽  
pp. 159-167 ◽  
Author(s):  
D. A. Rodin ◽  
S. D. Abbot ◽  
G. Saade ◽  
R. N. Clayton

ABSTRACT There are significant differences between rats and mice in the gonadal regulation of several aspects of gonadotroph function. To investigate whether these extend to the pretranslational regulation of FSH synthesis by gonadal steroids, we have measured FSH-β mRNA levels following gonadectomy and sex-steroid replacement and have related these to serum and pituitary FSH as a reflection of overall hormone synthesis. In ovariectomized rats, FSH-β mRNA levels increased by 8 h, decreased, and then rose progressively over the next 28 days. A similar pattern of response was observed in orchidectomized rats. In mice, there were progressive increases in FSH-β mRNA levels in both males and females following gonadectomy, without evidence of the early peaks observed in rats. In both species, the change in FSH-β mRNA levels after gonadectomy was greater in females than in males. These changes in FSH-β mRNA following gonadectomy were paralleled by changes in the serum FSH concentration. In ovariectomized female rats and mice, pituitary FSH stores increased by 8 h and 3 days respectively, whereas in male rats, pituitary FSH content did not rise until 10 days after orchidectomy. The most striking species difference was the marked and prolonged reduction of pituitary FSH after orchidectomy of mice. Treatment of rats and mice from the time of ovariectomy, with a dose of oestradiol that prevents increases in serum LH, only partially attenuated the rises in FSH-β mRNA and serum FSH and did not prevent the increase in pituitary FSH content. Treatment of intact or orchidectomized rats with testosterone suppressed FSH-β mRNA levels to 50% below intact control values without affecting pituitary FSH content. In mice, testosterone treatment for 10 days reduced the post-castration increase in FSH-β mRNA by only 26%, and prevented the fall in pituitary FSH content, although the increased serum concentration of FSH was unaffected. In conclusion: (1) there is a good correlation between FSH-β mRNA levels and overall FSH biosynthesis in male and female rats and female mice, but this relationship is less obvious in male mice where pituitary FSH stores are not increased; (2) the inability of oestradiol to prevent completely the post-ovariectomy increase in FSH-β mRNA and FSH synthesis in female rats and mice indicates either that other gonadal products are necessary or that higher doses of oestradiol are required than for complete suppression of LH synthesis; (3) whilst the post-gonadectomy increases in FSH-β mRNA are larger in the female of both species, there are no major differences between rats and mice in the regulation of FSH-β gene expression by sex steroids.


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