Mallory stained sections showed significant increase in coll

Mallory stained sections showed significant increase in collagen fiber deposition around the hepatic nodules together with significant increase in positive immune-reaction to α-SMA in TAA-treated group. This was in accordance with previous studies which reported that myofibroblasts which were developed form activated hepatic stellate amc 7 synthesis or perivascular fibroblast were the main cells producing the extracellular connective tissue (Schuppan et al., 2003). Concerning proliferation of hepatocytes, we detected a significant increase in optical density of PCNA positive nuclei in TAA-treated group. This was in agreement with some investigators who mentioned that in liver of control animals few hepatocytes showed positive immune expression for PCNA, while increased expression was noticed in TAA-treated animals. This could be attributed to response of hepatocytes to liver damage (Tousson et al., 2014). Histologically, both Rvs and silymarin treated groups showed some hepatocytes with acidophilic cytoplasm and central vesicular nuclei, while other hepatocytes were seen vacuolated. No inflammatory cells could be noticed. This was explained by some authors who reported that statins could reduce proinflammatory cytokines (Link et al., 2006). Rousuvastatin also decreased endothelial dysfunction in liver cirrhosis (Abraldes et al., 2007; Moreno et al., 2009). On the other hand, it was previously reported that silymarin produced a significant improvement in the structural, functional and architectural properties in cirrhotic livers (Salama 2012). Mechanism of action of silymarin was described by some authors who reported that it has antioxidant effects and acts as a membrane stabilizer. It also promotes regeneration of hepatocytes, decreases inflammation and prevents liver cirrhosis (Feher and Lenqyel, 2012) Moreover, silymarin, was reported to prevent binding of hepatotoxin to hepatocyte membrane, in addition to stimulation of rRNA polymerase and increasing protein formation (Dixita et al., 2007). All these effects might be the cause of improvement of histological structure of the liver and regeneration of hepatocyte observed in this study. It has been reported that TGFβ1 is secreted form renal cells and cells infiltrating renal interstitium (Border and Noble, 1998) and is considered a key mediator in the occurrence of renal fibrosis and inflammation (Lan and Chung, 2012). Our study showed a deterioration of renal functions and increasing renal expression of TGFβ1 accompanying induction of liver cirrhosis by TAA. Our findings were in agreement with the reports of who detected a significant deterioration of renal functions by TAA evidenced by elevation of renal oxidative stress markers and renal mitochondrial dysfunction. Histologically, the TAA-treated rats showed kidney congestion of glomerular capillaries, vacuolated tubular cells and thickening of the wall of some blood vessels were noticed. Dilated tubules were also seen in the renal medulla. Similarly Neveen and Mahmoud (2006) reported that in chronic renal disease induced by liver cirrhosis, cells of convoluted tubules were disturbed and swollen, some glomeruli were atrophied and hemorrhage was seen around blood vessels. In the current study, both Rvs and silymarin treated groups, cytoplasmic vacuolation and dilated tubules were still present. Significant increase in the mean area percentage of collagen fiber deposition was noticed in renal interstitium in TAA-treated group together with significant increase in positive immune reaction for α-SMA. Similarly Liu, et al., 2015 noticed increase expression of α-SMA positive myofibroblasts in the renal interstitium. Moreover, TGFB1 could increase secretion of collagen fiber deposition. TGFβ1 also inhibited degradation of extracellular matrix (Border and Noble,1998) and caused tubular epithelial-mesenchymal transition of renal epithelial cells to myofiobroblast cells which is responsible for collagen deposition in the renal interstitium (Lanju 2003). Other authors reported that when the kidney is exposed to injury, pericytes which surround the endothelial cells of blood capillaries detach and proliferate. Pericytesare the main source of myofibroblasts that cause renal fibrosis (Lin et al., 2008).