Local Insulin-Derived Amyloidosis Model Confronted with Silymarin: Histological Insights and Gene Expression of MMP, TNF-α, and IL-6
Amyloidosis is a heterogeneous group of protein deposition diseases associated with the presence of amyloid fibrils in tissues. Analogs of insulin that are used for treating diabetic patients (including regular insulin) can form amyloid fibrils, both in vitro and in vivo as reported in patients. The...
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MDPI AG
2022-04-01
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| author | Katia Azarfar Parichehreh Yaghmaei Mahsa M. Amoli Nasim Hayati-Roodbari Azadeh Ebrahim-Habibi |
| author_facet | Katia Azarfar Parichehreh Yaghmaei Mahsa M. Amoli Nasim Hayati-Roodbari Azadeh Ebrahim-Habibi |
| author_sort | Katia Azarfar |
| collection | DOAJ |
| description | Amyloidosis is a heterogeneous group of protein deposition diseases associated with the presence of amyloid fibrils in tissues. Analogs of insulin that are used for treating diabetic patients (including regular insulin) can form amyloid fibrils, both in vitro and in vivo as reported in patients. The main purpose of this study was the induction of localized insulin-generated amyloidosis and the observation of <i>silymarin</i> effects on this process. In order to obtain amyloid structures, regular insulin was incubated at 37 °C for 24 h. Congo red absorbance and transmission electron microscopy images validated the formation of amyloid fibrils. Those fibrils were then injected subcutaneously into rats once per day for 6, 12 or 18 consecutive days in the presence or absence of <i>silymarin</i>, and caused development of firm waxy masses. These masses were excised and stained with Hematoxylin and Eosin, Congo red and Thioflavin S. Histological examination showed adipose cells and connective tissue in which amyloid deposition was visible. Amyloids decreased in the presence of <i>silymarin</i>, and the same effect was observed when <i>silymarin</i> was added to normal insulin and injected subsequently. Furthermore, plasma concentrations of MMP2, TNF-α, and IL-6 inflammatory factors were measured, and their gene expression was locally assessed in the masses by immunohistochemistry. All three factors increased in the amyloidosis state, while <i>silymarin</i> had an attenuating effect on their plasma levels and gene expression. In conclusion, we believe that <i>silymarin</i> could be effective in counteracting insulin-generated local amyloidosis. |
| first_indexed | 2024-03-10T04:05:08Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:05:08Z |
| publishDate | 2022-04-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-345add1fcb3842cf854f5c385cc430522023-11-23T08:24:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01239495210.3390/ijms23094952Local Insulin-Derived Amyloidosis Model Confronted with Silymarin: Histological Insights and Gene Expression of MMP, TNF-α, and IL-6Katia Azarfar0Parichehreh Yaghmaei1Mahsa M. Amoli2Nasim Hayati-Roodbari3Azadeh Ebrahim-Habibi4Department of Biology, Faculty of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran 1477893855, IranDepartment of Biology, Faculty of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran 1477893855, IranMetabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran 1411413137, IranDepartment of Biology, Faculty of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran 1477893855, IranBiosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran 1411713137, IranAmyloidosis is a heterogeneous group of protein deposition diseases associated with the presence of amyloid fibrils in tissues. Analogs of insulin that are used for treating diabetic patients (including regular insulin) can form amyloid fibrils, both in vitro and in vivo as reported in patients. The main purpose of this study was the induction of localized insulin-generated amyloidosis and the observation of <i>silymarin</i> effects on this process. In order to obtain amyloid structures, regular insulin was incubated at 37 °C for 24 h. Congo red absorbance and transmission electron microscopy images validated the formation of amyloid fibrils. Those fibrils were then injected subcutaneously into rats once per day for 6, 12 or 18 consecutive days in the presence or absence of <i>silymarin</i>, and caused development of firm waxy masses. These masses were excised and stained with Hematoxylin and Eosin, Congo red and Thioflavin S. Histological examination showed adipose cells and connective tissue in which amyloid deposition was visible. Amyloids decreased in the presence of <i>silymarin</i>, and the same effect was observed when <i>silymarin</i> was added to normal insulin and injected subsequently. Furthermore, plasma concentrations of MMP2, TNF-α, and IL-6 inflammatory factors were measured, and their gene expression was locally assessed in the masses by immunohistochemistry. All three factors increased in the amyloidosis state, while <i>silymarin</i> had an attenuating effect on their plasma levels and gene expression. In conclusion, we believe that <i>silymarin</i> could be effective in counteracting insulin-generated local amyloidosis.https://www.mdpi.com/1422-0067/23/9/4952regular insulinamyloidosisaromatic compoundMMP2TNF-αIL-6 |
| spellingShingle | Katia Azarfar Parichehreh Yaghmaei Mahsa M. Amoli Nasim Hayati-Roodbari Azadeh Ebrahim-Habibi Local Insulin-Derived Amyloidosis Model Confronted with Silymarin: Histological Insights and Gene Expression of MMP, TNF-α, and IL-6 International Journal of Molecular Sciences regular insulin amyloidosis aromatic compound MMP2 TNF-α IL-6 |
| title | Local Insulin-Derived Amyloidosis Model Confronted with Silymarin: Histological Insights and Gene Expression of MMP, TNF-α, and IL-6 |
| title_full | Local Insulin-Derived Amyloidosis Model Confronted with Silymarin: Histological Insights and Gene Expression of MMP, TNF-α, and IL-6 |
| title_fullStr | Local Insulin-Derived Amyloidosis Model Confronted with Silymarin: Histological Insights and Gene Expression of MMP, TNF-α, and IL-6 |
| title_full_unstemmed | Local Insulin-Derived Amyloidosis Model Confronted with Silymarin: Histological Insights and Gene Expression of MMP, TNF-α, and IL-6 |
| title_short | Local Insulin-Derived Amyloidosis Model Confronted with Silymarin: Histological Insights and Gene Expression of MMP, TNF-α, and IL-6 |
| title_sort | local insulin derived amyloidosis model confronted with silymarin histological insights and gene expression of mmp tnf α and il 6 |
| topic | regular insulin amyloidosis aromatic compound MMP2 TNF-α IL-6 |
| url | https://www.mdpi.com/1422-0067/23/9/4952 |
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