Background:  Sorafenib is a standard drug used for advanced hepatocellular carcinoma but is often resistant and toxic. Its combination with epigallo-3-catechin gallate leads to reduced resistance and toxicity but an equally effective anti-angiogenic effect.Therefore, this study aims to assess the anti-angiogenic effect of standard-dose Sorafenib compared to the combination of low-dose Sorafenib and epigallo-3-catechin gallate. Methods:  We conducted an animal study and double-blind, randomized controlled trials. A total of 25 male Wistar rats (7-weeks-old) were randomly divided into four groups, namely Sham (K), Control (O), a combination of low-dose Sorafenib and epigallo-3-catechin gallate group (X1), and standard-dose Sorafenib group (X2). All groups were injected with N-Nitrosodiethylamine 70 mg/kg body weight (BW) intraperitoneally for ten weeks, except the Sham group. After the development of hepatocellular carcinoma, X1 and X2 were treated for two weeks. Subsequently, liver tissues were examined for vascular endothelial growth factor (VEGF) level and microvascular density expression. Results: There was a significant difference (p=0.007) in the level of VEGF between group X1 (low dose Sorafenib + EGCG) and X2 (Standard dose Sorafenib). However, the differences in VEGF levels of group X1 and X2 compared to group O(Control) were significantly lower, with values p=0.000136 and p=0.019, respectively. The expression of microvascular density between groups X1 and X2  was not entirely different. Meanwhile, a significant difference (p<0.05) was discovered when both groups were compared with the control group. Conclusion: The combination of low-dose Sorafenib with epigallo-3-catechin gallate is superior in reducing the level of VEGF compared to standard-dose Sorafenib and is better than the control. Standard-dose Sorafenib and the combination of low-dose Sorafenib and epigallo-3-catechin gallate have similar effectivity in reducing the expression of microvascular density and could prevent resistance and lower toxicity effects.

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Background:  Sorafenib is an expensive standard drug used for advanced hepatocellular carcinoma. Its combination with epigallo-3-catechin gallate leads to a reduced cost but equally effective anti-angiogenic effect. Therefore, this study aims to assess the anti-angiogenic effect of standard-dose Sorafenib compared to the combination of low-dose Sorafenib and epigallo-3-catechin gallate. Methods:  A total of 25 male Wistar rats (7-weeks-old) were randomly divided into 4 groups, namely Sham (K), Control (O), combination of low-dose Sorafenib and epigallo-3-catechin gallate group (X1), and standard-dose Sorafenib group (X2). All groups were injected with N-Nitrosodiethylamine 70 mg/kg bodyweight (BW) intraperitoneally for 10 weeks, except the Sham group. After the development of hepatocellular carcinoma, X1 and X2 were treated for 2 weeks. Subsequently, the level of vascular endothelial growth factor (VEGF) and expression of microvascular density was examined using liver tissues. Results: There was a significant difference (p=0.007) in the level of VEGF between the group X1 (106,682 ± 41,024) and X2 (214,5162 ± 67,71652). However, the differences in VEGF level of group X1 and X2 compared to group O (318,101 ± 55,078) were significantly lower, with values p=0.000136 and p=0.019, respectively. The expression of microvascular density between groups X1 (36 ± 4,416) and X2 (26,2 ± 4,55) was not significantly different. Meanwhile, a significant difference (p<0.05) was discovered when both groups were compared with group O (176 ± 19). Conclusion: The combination of low-dose Sorafenib with epigallo-3-catechin gallate is superior in reducing the level of VEGF compared to standard-dose Sorafenib and is better than the control. Standard-dose Sorafenib as well as the combination of low-dose Sorafenib and epigallo-3-catechin gallate have similar effectivity to reduce the expression of microvascular density.

Introduction: Liver fibrosis is a healing response of the liver to injury by depositing excessive extracellular matrix proteins. Although this fibrosis has a strong impact on survival following resection, there is no therapeutic guideline so far for liver fibrosis. Platelet-derived Growth Factor (PDGF) is the most potent mitogen of Hepatic Stellate Cells (HSC) which started liver fibrogenesis. Mesenchymal Stem Cells (MSCs) have an anti-fibrotic effect by controlling inflammation and HSC immunomodulation, while Bovine Colostrum (BC) has an antifibrotic effect by its antioxidant capacity and growth factor content. However, their effect was only studied in the non-resected fibrotic liver and their combination is never been studied. our study aimed to examine the effects of MSC, BC and their combination on PDGF and fibrosis level in the fibrotic liver after resection. Material and methods: Twenty-five Sprague-Dawley rats with fibrotic liver were randomly assigned to BC, MSC, MSC+BC, control, and sham groups. Hepatectomy 50% was carried out except for the sham group. The 106MSCs were given intraparenchymal liver, while BC (15 μL/g) was given orally for 5 days/week until day 10. The PDGF plasma level was assessed on days 3, 7, and 10. The histopathologic examination of the liver remnant was done on day 10 using Metavir Scoring System. Result: MSC+BC significantly increased PDGF level on day 3 followed by a significant decrease on day 10 (p<0.001). The Metavir mean score was 1.2 in the MSC+BC group. Conclusion: MSC+BC combination can improve liver fibrosis after hepatectomy of liver fibrosis rats by preventing post-hepatectomy fibrogenesis. Bangladesh Journal of Medical Science Vol. 21 No. 02 April’22 Page : 262-270