(Folia Morphol 2015; 74, 4: 447-457)

Micronized purified flavonoid fraction (MPFF, Daflon ® ) is a phlebotonic drug widely used in chronic venous or lymphatic insufficiency. We aimed to investigate the effects of MPFF on hepatic and brain oxidative stress and on liver injury caused by lipopolysaccharide (LPS) in rats. MPFF (4.5, 9, or 18 mg/kg) or saline was administered orally for two days prior to intraperitoneal (i.p.) LPS (300 μg/kg) and at time of LPS administration. Rats were euthanized 4 h after LPS injection. The administration of LPS increased oxidative stress in brain and liver tissue. Malondialdehyde (MDA) increased by 193.5 and 191.8%, reduced glutathione (GSH) decreased by 73.8 and 70.8% and nitric oxide increased by 118.2 and 151.7% in the brain and liver, respectively. Serum paraoxonase 1 (PON1) activity decreased by 42.6%. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were raised by 101.8, 93.6, and 223.2%, respectively. Rats treated with MPFF at 9 and 18 mg/kg showed decreased brain MDA (27.5-34%), nitrite (25.5-41%) and increased GSH (27.2-74.1%). In the liver, MDA decreased by 16.4-59.8%, nitrite decreased by 54.7-56.7%, and GSH increased by 15.2-70.5% with MPFF at 4.5, 9, or 18 mg/kg, respectively. Serum PON1 activity showed 41-65.9% increments with MPFF. Significant reductions in serum AST, ALT, and ALP were seen after treatment with MPFF. Moreover, the degree of histological damage, expression of the inducible form of nitric oxide synthase and the apoptotic enzyme caspase-3 in the liver were substantially reduced. MPFF thus prevented the increased oxidative stress and inflammation in brain and liver as well as the liver dysfunction caused by endotoxemia in the rat.

The present work aimed to evaluate the combined therapeutic effect of both solubilized Coenzyme Q10 and Silymarin on thioacetamide (TAA) induced liver injury. A total of thirty adult male albino rats, weighing 200±10 g were allocated into five groups. Hepatic injury was induced by Thioacetamide (TAA) 20 mg/ kg b wt for 28 days by intraperitoneal injection twice a week. On the other hand, solubilized Coenzyme Q10 (20 mg/kg) & Silymarin (50 mg/kg) were taken orally for 28 days. Upon using the aspartate and platelet ratio index (APRI) & aspartate aminotransferase-alanine aminotransferase ratio (AAR), the TAA group recording the highest values while treatments using Coenzyme Q10 and or Silymarin could decrease theirs values near the control one. However, solubilized CoQ10 could attenuate liver injury induced by TAA via balanced oxidative stress symbols (GSH, GSSG), NO level, and down-regulation gene expression of fibrotic markers TGF-β, collagen-1α, and, TIMP1 as well as enhanced the expression for MMP2 and cytochrome P 450 (CYP 2E1& CYP 3A2). Collectively, solubilized CoQ10 singly or combined with Silymarin showed higher therapeutic impacts more than or equivalents to Silymarin singly treatment for liver fibrosis induced by TAA.