Comparative Effects of Crocin and Losartan on RAGE, TGF‐β, TNF‐α Gene Expression and Histopathological Changes of the Liver Tissue in Rats With Diabetes
ABSTRACT Background and Objectives AGEs, via RAGE, increase the development of hyperglycemia‐induced liver damage, and blocking this axis is associated with a reduction in liver disease progression. The goal of this study was to determine how crocin and losartan influenced RAGE, TNF‐α and TGF‐β gene...
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Wiley
2025-01-01
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| Series: | Endocrinology, Diabetes & Metabolism |
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| Online Access: | https://doi.org/10.1002/edm2.70016 |
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| author | Shahnaz Rajabi Yaser Mohammadi Hamid Kabiri‐rad Mahdiyeh Rajabi‐moghaddam Azam Rezaei Farimani |
| author_facet | Shahnaz Rajabi Yaser Mohammadi Hamid Kabiri‐rad Mahdiyeh Rajabi‐moghaddam Azam Rezaei Farimani |
| author_sort | Shahnaz Rajabi |
| collection | DOAJ |
| description | ABSTRACT Background and Objectives AGEs, via RAGE, increase the development of hyperglycemia‐induced liver damage, and blocking this axis is associated with a reduction in liver disease progression. The goal of this study was to determine how crocin and losartan influenced RAGE, TNF‐α and TGF‐β gene expression in diabetic rats, as well as histological changes in liver tissue. Materials and Methods Diabetes was induced in 40 male Wistar rats using Streptozotocin (50 mg/kg, IP). There were five groups of rats: diabetic and healthy groups, diabetic rats given crocin (50 mg/kg), losartan (25 mg/kg) and both (crocin + Los). Serum glucose, ALT and AST levels were measured 4 weeks later. qPCR was used to examine the TNF‐α, TGF‐β and RAGE gene expression in liver tissue. Results Crocin was found to be effective in lowering FBG in the diabetes group. The serum levels of ALT and AST decreased in all treated groups, but this decrease was significant in the crocin + Los group (p < 0.05). The relative expression of RAGE, TNF‐α and TGF‐β genes was significantly higher in the diabetes group compared to the healthy group. The expression of these genes decreased in groups treated with crocin and Losartan compared to the diabetes group. The highest reduction in RAGE and TGF‐β gene expression was reported in those treated with crocin + Los. Histopathology results showed that the diabetes group had more bile ducts and necrosis than the healthy control group, which had no tissue changes. Hepatocyte degeneration, bile duct proliferation, inflammatory changes and hepatocyte necrosis were mild in the treated groups, but no hepatocyte necrosis was observed in the crocin + Los group. Conclusion Crocin may be a feasible therapeutic agent for treating diabetes and its symptoms when combined with pharmaceutical medications. Human research is still needed to reach clear conclusions. |
| format | Article |
| id | doaj-art-dc8b27bfcdfd45dd97343014deaf41a5 |
| institution | Kabale University |
| issn | 2398-9238 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Endocrinology, Diabetes & Metabolism |
| spelling | doaj-art-dc8b27bfcdfd45dd97343014deaf41a52025-01-25T18:20:28ZengWileyEndocrinology, Diabetes & Metabolism2398-92382025-01-0181n/an/a10.1002/edm2.70016Comparative Effects of Crocin and Losartan on RAGE, TGF‐β, TNF‐α Gene Expression and Histopathological Changes of the Liver Tissue in Rats With DiabetesShahnaz Rajabi0Yaser Mohammadi1Hamid Kabiri‐rad2Mahdiyeh Rajabi‐moghaddam3Azam Rezaei Farimani4Student Research Committee Birjand University of Medical Sciences Birjand IranDepartment of Biochemistry, School of Medicine Iran University of Medical Sciences Tehran IranCellular and Molecular Research Center Birjand University of Medical Sciences Birjand IranDepartment of Pathology, School of Medicine Birjand University of Medical Sciences Birjand IranDepartment of Clinical Biochemistry, School of Medicine Birjand University of Medical Sciences Birjand IranABSTRACT Background and Objectives AGEs, via RAGE, increase the development of hyperglycemia‐induced liver damage, and blocking this axis is associated with a reduction in liver disease progression. The goal of this study was to determine how crocin and losartan influenced RAGE, TNF‐α and TGF‐β gene expression in diabetic rats, as well as histological changes in liver tissue. Materials and Methods Diabetes was induced in 40 male Wistar rats using Streptozotocin (50 mg/kg, IP). There were five groups of rats: diabetic and healthy groups, diabetic rats given crocin (50 mg/kg), losartan (25 mg/kg) and both (crocin + Los). Serum glucose, ALT and AST levels were measured 4 weeks later. qPCR was used to examine the TNF‐α, TGF‐β and RAGE gene expression in liver tissue. Results Crocin was found to be effective in lowering FBG in the diabetes group. The serum levels of ALT and AST decreased in all treated groups, but this decrease was significant in the crocin + Los group (p < 0.05). The relative expression of RAGE, TNF‐α and TGF‐β genes was significantly higher in the diabetes group compared to the healthy group. The expression of these genes decreased in groups treated with crocin and Losartan compared to the diabetes group. The highest reduction in RAGE and TGF‐β gene expression was reported in those treated with crocin + Los. Histopathology results showed that the diabetes group had more bile ducts and necrosis than the healthy control group, which had no tissue changes. Hepatocyte degeneration, bile duct proliferation, inflammatory changes and hepatocyte necrosis were mild in the treated groups, but no hepatocyte necrosis was observed in the crocin + Los group. Conclusion Crocin may be a feasible therapeutic agent for treating diabetes and its symptoms when combined with pharmaceutical medications. Human research is still needed to reach clear conclusions.https://doi.org/10.1002/edm2.70016crocindiabetesinflammatory markersliver diseaselosartanOxidative stress |
| spellingShingle | Shahnaz Rajabi Yaser Mohammadi Hamid Kabiri‐rad Mahdiyeh Rajabi‐moghaddam Azam Rezaei Farimani Comparative Effects of Crocin and Losartan on RAGE, TGF‐β, TNF‐α Gene Expression and Histopathological Changes of the Liver Tissue in Rats With Diabetes Endocrinology, Diabetes & Metabolism crocin diabetes inflammatory markers liver disease losartan Oxidative stress |
| title | Comparative Effects of Crocin and Losartan on RAGE, TGF‐β, TNF‐α Gene Expression and Histopathological Changes of the Liver Tissue in Rats With Diabetes |
| title_full | Comparative Effects of Crocin and Losartan on RAGE, TGF‐β, TNF‐α Gene Expression and Histopathological Changes of the Liver Tissue in Rats With Diabetes |
| title_fullStr | Comparative Effects of Crocin and Losartan on RAGE, TGF‐β, TNF‐α Gene Expression and Histopathological Changes of the Liver Tissue in Rats With Diabetes |
| title_full_unstemmed | Comparative Effects of Crocin and Losartan on RAGE, TGF‐β, TNF‐α Gene Expression and Histopathological Changes of the Liver Tissue in Rats With Diabetes |
| title_short | Comparative Effects of Crocin and Losartan on RAGE, TGF‐β, TNF‐α Gene Expression and Histopathological Changes of the Liver Tissue in Rats With Diabetes |
| title_sort | comparative effects of crocin and losartan on rage tgf β tnf α gene expression and histopathological changes of the liver tissue in rats with diabetes |
| topic | crocin diabetes inflammatory markers liver disease losartan Oxidative stress |
| url | https://doi.org/10.1002/edm2.70016 |
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