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  • We found that silymarin induced more

    2021-10-18

    We found that silymarin induced more improvement of renal functions compared to Rvs. Our results were in agreement with previous studies. The effect of silymarin has been tested in alloxan-induced diabetes mellitus models in rats. Alloxan produces reactive oxygen species which injure renal tissue. Silymarin was administrated 20 days after 9 weeks treatment with alloxan and it was effective on the renal tissue injuries. It has antioxidant effects via increase of gene expression of antioxidant enzymes and a number of the most important protection mechanisms against free radicals' damage containing superoxide dismutase, glutathione peroxidase, and catalase. Therefore, researchers concluded that silymarin could be used as a drug for diabetic nephropathy therapy (Soto et al., 2010). In the present study, silymarin induced moderate diuretic effect noticed by the increase in urine volume/day. This is in agreement with de la Lastra et al., 1991 who observed a diuretic behavior for silymarin similar to potassium-sparing diuretics. This may add a therapeutic benefit to silymarin in cirrhotic patient who are intolerable to the adverse effects of the potassium loosing diuretics. Histologically, both Rvs and silymarin treated groups showed a significant decrease in the mean area percentage of collagen fiber deposition compared to TAA-treated group. It has been reported that statins decrease proliferation of mesangial and vascular smooth muscle perifosine (Campese et al., 2005), which might explain the decrease in the collagen fibers in the current study in TAA Rvs-treated group. FXR is one of nuclear hormone receptors and it has a rising role in the control of NO production through targeting DDAH-1. Our results showed that TAA decreased expression of both hepatic and renal FXR. Moreover, decrease hepatic and renal FXR was associated with decrease expression of DDAH-1 and eNOS. Interestingly, administration of silymarin and Rvs was associated by increasing expression of hepatic and renal FXR, DDAH1 and eNOS, decreasing expression of TGFβ1 and hepatorenal therapeutic as evidenced by the results of hepatic and renal function tests. The positive association detected through our results between hepatic and renal FXR expression could explain the hepatorenal therapeutic effect of Rvs and silymarin through increasing expression of FXR. FXR facilitates the tubular secretory mechanisms (Herman-Edelstein et al., 2018), this may explain the moderate increase in urine volume by both drugs. Naturally, the improvement of liver functions enhances bile acid synthesis which is considered the main endogenous legend of renal FXR (Herman-Edelstein et al., 2018). The negative association between hepatic FXR and TGFβ1 and the positive association between renal FXR and both DDAH-1 and eNOS shed light on their therapeutic mechanisms. According to our result, they protect the liver and the kidney through increasing expression of FXR which increased expression of DDAH-1 resulting into increasing expression of eNOS. In agreement with our results, researchers found that FXR was reduced in liver cirrhosis and that its activation had a beneficial effect on liver cirrhosis as well as renal functions (Hu et al., 2012, Ding et al., 2015). The weak negative correlation between renal FXR and renal TGFβ1 expression in TAA-Rvs and TAA-silymarin treated groups could be explained by the enhancement effect of Rvs and silymarin on FXR more than their inhibitory effect on TGFβ1, thus giving Rvs and silymarin the priority in the management of hepatic nephropathy rather than primary renal affection. Also, Hu et al., 2006 demonstrated that FXR agonists increased expression of DDAH1 gene with subsequent reduction of its substrate ADMA. Since ADMA is a nitric oxide synthase inhibitor, inhibition of ADMA by FXR agonists could play a protective role against the onset and progression of renal diseases resulting from decrease NO production. Accordingly, it seems that prevention of further liver deterioration together with renal functions preservation is the main target in managing cirrhotic patients.