TY - JOUR
T1 - Antifibrotic effect of diethylcarbamazine combined with hesperidin against ethanol induced liver fibrosis in rats
AU - El-Sisi, Alaa El Din El Sayed
AU - Sokar, Samia Salim
AU - Shebl, Abdelhadi Mohamed
AU - Mohamed, Dina Zakaria
N1 - Publisher Copyright:
© 2017 Elsevier Masson SAS
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Chronic alcohol consumption leads to extracellular matrix hyperplasia and liver fibrosis with a great role of hepatic stellate cell (HSC) activation in this process. The present study was designed to investigate the possible protective effects of diethylcarbamazine (DEC) (50 mg/kg, acting as an anti-inflammatory drug, interferes with the arachidonic acid metabolism) when administrated in combination with hesperidin (HDN) (200 mg/kg, a flavanone glycoside with potent antioxidant and anti-inflammatory activities) against alcoholic liver fibrosis in wistar rats compared to silymarin (Sil) (100 mg/kg). Liver fibrosis was induced in rats using ethanol (EtOH) (1 ml/100 g/day, p.o.) twice a week for seven weeks. Then, tissue and blood samples were collected to assess the protective effect of DEC + HDN combination. Our results indicated that DEC when combined with HDN blunted EtOH-induced necroinflammation and elevation of liver injury parameters in serum. Besides, attenuated EtOH- induced liver fibrosis, as demonstrated by hepatic histopathology scoring and 4-hydroxyproline content. The mechanisms behind these beneficial effects of both DEC and HDN were also elucidated. These include (1) counteracting hepatic oxidative stress and augmenting hepatic antioxidants; (2) inhibiting the activation of NF-κB as indicated by preventing release of hepatic IL6; (3) preventing the activation of hepatic stellate cells (HSCs), as denoted by reducing a-smooth muscle actin (a-SMA) expression in the liver; and (4) inhibiting the fibrogenesis response of HSCs, as indicated by inhibiting serum transforming growth factor-b1 (TGF-b1). Our study indicates a novel hepatoprotective effect when DEC was co-administered with HDN against liver fibrosis.
AB - Chronic alcohol consumption leads to extracellular matrix hyperplasia and liver fibrosis with a great role of hepatic stellate cell (HSC) activation in this process. The present study was designed to investigate the possible protective effects of diethylcarbamazine (DEC) (50 mg/kg, acting as an anti-inflammatory drug, interferes with the arachidonic acid metabolism) when administrated in combination with hesperidin (HDN) (200 mg/kg, a flavanone glycoside with potent antioxidant and anti-inflammatory activities) against alcoholic liver fibrosis in wistar rats compared to silymarin (Sil) (100 mg/kg). Liver fibrosis was induced in rats using ethanol (EtOH) (1 ml/100 g/day, p.o.) twice a week for seven weeks. Then, tissue and blood samples were collected to assess the protective effect of DEC + HDN combination. Our results indicated that DEC when combined with HDN blunted EtOH-induced necroinflammation and elevation of liver injury parameters in serum. Besides, attenuated EtOH- induced liver fibrosis, as demonstrated by hepatic histopathology scoring and 4-hydroxyproline content. The mechanisms behind these beneficial effects of both DEC and HDN were also elucidated. These include (1) counteracting hepatic oxidative stress and augmenting hepatic antioxidants; (2) inhibiting the activation of NF-κB as indicated by preventing release of hepatic IL6; (3) preventing the activation of hepatic stellate cells (HSCs), as denoted by reducing a-smooth muscle actin (a-SMA) expression in the liver; and (4) inhibiting the fibrogenesis response of HSCs, as indicated by inhibiting serum transforming growth factor-b1 (TGF-b1). Our study indicates a novel hepatoprotective effect when DEC was co-administered with HDN against liver fibrosis.
KW - Alcohol
KW - IL-6
KW - Liver enzymes
KW - Oxidative stress
KW - Silymarin
KW - TGF-β1
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U2 - 10.1016/j.biopha.2017.03.013
DO - 10.1016/j.biopha.2017.03.013
M3 - Article
C2 - 28320086
AN - SCOPUS:85015393496
SN - 0753-3322
VL - 89
SP - 1196
EP - 1206
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
ER -