This study aimed to evaluate the antitumor effect of chlorogenic acid (CGA) alone and in combination with doxorubicin (DOX) in solid Ehrlich carcinoma (SEC) model in mice. In addition, we investigated the possible cardioprotective effect of CGA against DOX-induced cardiotoxicity. CGA, DOX and their combination were given for 21 days in mice bearing SEC. Tumor volume and weight were measured, and serum CRP was determined by latex immunoassay. Moreover, mRNA expressions of TRAIL, TRAILR2, FasL, Fas, caspase-3 and Bcl-2 were measured using RT-PCR. Histopathological examination of tumor and cardiac tissues was carried out using hematoxylin and eosin. Active caspase-3 was detected by immunohistochemistry. CGA and/or DOX treatment showed a remarkable decrease in solid tumor volume and weight. CGA and/or DOX groups revealed upregulation in gene expressions of TRAIL/TRAILR2, FasL/Fas and caspase-3 genes and downregulation of Bcl-2 gene expression, as well as a marked increase in active caspase-3 expression. Moreover, CGA and DOX combination significantly decreased MDA and increased GSH levels in tumor tissues and also reduced the level of serum CRP, CK-MB and LDH as compared to DOX group. In conclusion, CGA has the ability not only to enhance the antitumor activity of DOX but also protects against DOX-induced cardiotoxicity.
The present study aimed to investigate the hepatoprotective effect of sesamol (SML), a nutritional phenolic compound obtained from sesame seeds, in liver fibrosis induced by thioacetamide (TAA) in rats and to explore the underlying mechanisms. Thirty-two male Sprague–Dawley rats were equally divided into four groups: control, TAA, TAA + SML 50 mg/kg, and TAA + SML 100 mg/kg groups. Liver functions and hepatic contents of glutathione (GSH) and malondialdehyde (MDA) were measured colorimetrically. Gene expressions of lysophosphatidic acid receptor (LPAR)-1 and -3, connective tissue growth factor (CTGF), transforming growth factor (TGF)-β1, small mothers against decapentaplegic (Smad)-3 and -7, α-smooth muscle actin (α-SMA), and cytokeratin 19 (CK19) were analyzed by qRT-PCR. Moreover, phosphorylated Smad3 (pSmad3) was quantified by ELISA. Additionally, TGF-β1, α-SMA, CK19, and vascular endothelial growth factor (VEGF) protein concentrations were semi-quantitatively analyzed by immunostaining of liver sections. SML treatment markedly improved liver index and liver functions. Moreover, SML protected against liver fibrosis in a dose-dependent manner as indicated by down-regulation of LPAR1, LPAR3, CTGF, TGF-β1/Smad3, and α-SMA expressions and a decrease in pSmad3 level, as well as an up-regulation of Smad7 expression. In addition, SML suppressed ductular reaction hinted by the decrease in CK19 expression. These results reveal the anti-fibrotic effect of SML against liver fibrosis that might be attributed to down-regulation of LPAR1/3 expressions, inhibition of TGF-β1/Smad3 pathway, and ductular reaction.
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