Insights into hepatic and renal FXR/DDAH-1/eNOS pathway and its role in the potential benefit of rosuvastatin and silymarin in hepatic nephropathy
| Autor: | Enas Samir Nabih, Dalia Alaa El-Din Aly El-Waseef, Yosra M. Magdy, Omnyah A. El-Kharashi, Abeer A. Abd El Samad |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Liver Cirrhosis Male Cirrhosis Nitric Oxide Synthase Type III medicine.drug_class Clinical Biochemistry Receptors Cytoplasmic and Nuclear Pharmacology Pathology and Forensic Medicine Nephropathy Amidohydrolases 03 medical and health sciences chemistry.chemical_compound Enos medicine Animals Rosuvastatin Rats Wistar Rosuvastatin Calcium Molecular Biology Kidney Bile acid biology business.industry medicine.disease biology.organism_classification Rats 030104 developmental biology medicine.anatomical_structure chemistry Farnesoid X receptor Kidney Diseases Thioacetamide business medicine.drug Signal Transduction Silymarin |
| Zdroj: | Experimental and molecular pathology. 105(3) |
| ISSN: | 1096-0945 |
| Popis: | Objectives The repression of renal Farnesoid X Receptor (FXR) had been shown to result from lack of bile acid production from cirrhotic liver. We hypothesized that silymarin and rosuvastatin (Rvs) could have a hepatorenal therapeutic effects in hepatic nephropathy through induction of FXR. Methods Forty two male Wistar rats were used; naive (n = 12); six of them were sacrificed after 4 weeks and six continued till the end of the experiment. Thirty rats were treated as follows: Rvs, silymarin, thioacetamide (TAA), TAA + Rvs and TAA + silymarin. Liver and kidney function tests as well as the renal and hepatic expression of transforming growth factor β1 (TGFβ1), FXR, dimethylarginine dimethylaminohydrolase-1 (DDAH-1) and eNOS were performed. Histological and immuno-histochemical studies of liver and kidney were also done. Results TAA-inducted liver cirrhosis was associated with significant deterioration of liver and renal functions together with increasing expression of hepatic and renal TGFβ1 and decreasing expression of hepatic and renal FXR, DDAH-1 and eNOS. Giving silymarin or Rvs induced hepatic and renal improvement which was evidenced biochemically and histologically. Significant positive correlation was detected between all the investigated biomarkers except for the correlation between FXR and TGFβ1 which was negative. Conclusions In conclusion, liver cirrhosis is associated with deterioration of renal functions. Silymarin and Rvs have a potential hepatorenal therapeutic benefit through simultaneous enhancement of FXR/DDAH-1/eNOS pathway in both organs. |
| Databáze: | OpenAIRE |
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