Antifibrotic effect of diethylcarbamazine combined with hesperidin against ethanol induced liver fibrosis in rats.
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) (50mg/kg, acting as an anti-inflammatory drug, interferes with the arachidonic acid metabolism) when administrated in combination with hesperidin (HDN) (200mg/kg, a flavanone glycoside with potent antioxidant and anti-inflammatory activities) against alcoholic liver fibrosis in wistar rats compared to silymarin (Sil) (100mg/kg). Liver fibrosis was induced in rats using ethanol (EtOH) (1ml/100g/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.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt. Electronic address: sisialadin@yahoo.com.
Alaa El-Din El-Sayed
AEE
El-Sisi
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt. Electronic address: dr_samia_sokar@yahoo.com.
Samia Salim
SS
Sokar
Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. Electronic address: Abdelhadi.shebl@yahoo.com.
Abdelhadi Mohamed
AM
Shebl
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt. Electronic address: m_halem1986@yahoo.com.
Dina Zakaria
DZ
Mohamed
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004049:Diethylcarbamazine / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D006569:Hesperidin / Q000494:pharmacology*; D006909:Hydroxyproline / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012838:Silymarin / Q000494:pharmacology
D000975:Antioxidants; D015850:Interleukin-6; D016328:NF-kappa B; D020011:Protective Agents; D012838:Silymarin; D000431:Ethanol; D006569:Hesperidin; D006909:Hydroxyproline; D004049:Diethylcarbamazine
Alcohol; IL-6; Liver enzymes; Oxidative stress; Silymarin; TGF-β1