Effect of ginseng extract on the TGF-ß1 signaling pathway in CCl4-induced liver fibrosis in rats.

BACKGROUND: Liver diseases are major global health problems. Ginseng extract has antioxidant, immune-modulatory and anti-inflammatory activities. This study investigated the effect of ginseng extract on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. METHODS: Male Wistar rats were divided into four groups: control group, ginseng group, CCl4 group and CCl4 + ginseng group. Liver injury was induced by the intraperitoneal (I.P) injection of 3 ml/kg CCl4 (30% in olive oil) weekly for 8 weeks. The control group was I.P injected with olive oil. The expression of genes encoding transforming growth factor beta (TGF-ß), type I TGF-ß receptor (TßR-1), type II TGF-ß receptor (TßR-II), mothers against decapentaplegic homolog 2 (Smad2), Smad3, Smad4, matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor matrix metalloproteinase-1 (TIMP-1), Collagen 1a2 (Col1a2), Collagen 3a1 (Col3a1), interleukin-8 (IL-8) and interleukin -10 (IL-10) were measured by real-time PCR. RESULTS: Treatment with ginseng extract decreased hepatic fat deposition and lowered hepatic reticular fiber accumulation compared with the CCl4 group. The CCl4 group showed a significant increase in hepatotoxicity biomarkers and up-regulation of the expression of genes encoding TGF-ß, TßR-I, TßR-II, MMP2, MMP9, Smad-2,-3, -4, and IL-8 compared with the control group. However, CCl4 administration resulted in the significant down-regulation of IL-10 mRNA expression compared with the control group. Interestingly, ginseng extract supplementation completely reversed the biochemical markers of hepatotoxicity and the gene expression alterations induced by CCl4. CONCLUSION: ginseng extract had an anti-fibrosis effect via the regulation of the TGF-ß1/Smad signaling pathway in the CCl4-induced liver fibrosis model. The major target was the inhibition of the expression of TGF-ß1, Smad2, and Smad3.

Treatment with aliskiren ameliorates tacrolimus-induced nephrotoxicity in rats.

INTRODUCTION: Tacrolimus is frequently used as immunosuppressive agent in organ transplantation but its clinical use is limited due to its marked nephrotoxicity. MATERIALS AND METHODS: Male Wistar albino rats weighing 150-200 g (10-12 weeks old) were used. Animals were divided into four groups. Group 1 served as control group and received normal saline, group 2 served as toxic group and received 2 mg/kg tacrolimus i.p., group 3 served as treatment group and received 2 mg/kg tacrolimus i.p. followed by 2 mg/kg aliskiren orally and group 4 served as drug per se group and received 2 mg/kg aliskiren orally. Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically. RESULTS: Treatment with aliskiren decreased the tacrolimus-induced changes in biochemical markers of nephrotoxicity such as blood urea nitrogen and creatinine. Aliskiren also attenuated the effects of tacrolimus on oxidative stress parameters such as malondialdehyde, reduced glutathione and catalase. Histopathological and ultrastructural studies showed that aliskiren attenuated tacrolimus-induced renal damage. CONCLUSION: These results suggest that aliskiren has protective effects against tacrolimus-induced nephrotoxicity; implying that renin inhibitor may counteract nephrotic syndrome associated with immunosuppressant use.

Protection against tacrolimus-induced cardiotoxicity in rats by olmesartan and aliskiren.

CONTEXT: Tacrolimus (TAC), a calcineurin inhibitor, is commonly used as an immunosuppressive agent in organ transplantation, but its clinical use may be limited due to cardiotoxicity. Olmesartan (OLM; angiotensin receptor blocker) and aliskiren (ALK; renin inhibitor) may attenuate cardiotoxicity induced by TAC by inhibition of renin-angiotensin aldosterone system. OBJECTIVE: The aim of this study was to evaluate the effect of OLM and ALK on TAC-induced cardiotoxicity. MATERIALS AND METHODS: Male Wistar albino rats weighing 200-250 g (10-12 weeks old) were used in this study. Animals were divided into four groups. Group 1 received normal saline, group 2 received TAC (2 mg/kg, intraperitoneally for 14 d), group 3 received OLM (2 mg/kg, p.o. for 28 d) + TAC and group 4 received ALK (50 mg/kg, p.o. for 28 d) + TAC. TAC-induced cardiotoxicity was assessed biochemically and histopathologically. RESULTS: Treatment with OLM or ALK decreased the TAC-induced changes in biochemical markers of cardiotoxicity such as serum aspartate transaminase, creatine kinase and lactate dehydrogenase. OLM or ALK also attenuated the effects of TAC on oxidant-antioxidant parameters such as malondialdehyde, reduced glutathione and catalase. Histopathological and ultrastructural studies showed that OLM or ALK also attenuated TAC-induced cardiotoxicity. DISCUSSION AND CONCLUSION: These results suggest that OLM as well as ALK has protective effects against TAC-induced cardiotoxicity; implying that angiotensin receptor blocker or renin inhibitor, respectively, may counteract cardiotoxicity associated with immunosuppressant use.