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Insights into hepatic and renal FXR/DDAH-1/eNOS pathway and its role in the potential benefit of rosuvastatin and silymarin in hepatic nephropathy.

Authors: Magdy, Yosra M  El-Kharashi, Omnyah A  El-Waseef, Dalia A A  Nabih, Enas S  Abd El Samad, Abeer A 
Citation: Magdy YM, etal., Exp Mol Pathol. 2018 Dec;105(3):293-310. doi: 10.1016/j.yexmp.2018.10.004. Epub 2018 Oct 9.
Pubmed: (View Article at PubMed) PMID:30308196
DOI: Full-text: DOI:10.1016/j.yexmp.2018.10.004


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; naïve (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.

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CRRD Object Information
CRRD ID: 15042865
Created: 2019-12-12
Species: All species
Last Modified: 2019-12-12
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.