Biochemical studies on the effect of prostaglandin inhibitors and willow bark extract on liver cirrhosis induced by acetylsalicylate in rats

Prostaglandins (PGs) are arachidonic acid metabolites produced by the action of the enzyme cyclooxygenase (COX). Although PGs are important mediators of inflammation in various diseases, The deciduous herb, Salix mucronata Thunb (commonly called cape silver willow or safsaf willow), is widely distributed along the Nile River in Egypt. Like other willow trees, extracts from safsaf have also been used in traditional medicine. The anti-inflammatory effects of Salix mucronata are the inhibition of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) leading to the inhibition of prostaglandin synthesis. The study aims to assess the induced cirrhotic effect of high doses of prostaglandin inhibitors as acetylsalicylate administration on the liver of rats to determine the protective impact of willow bark (Salix mucronata) extract on liver cirrhosis in rats with studying the role of cyclooxygenases (COX-1) and (COX-2) in diagnosis and prognosis of liver cirrhosis. Material and methods:
For this study, a total of 68 male albino rats weighing 90- 100 gm were obtained from the Holding company for Biological Products and Vaccines (Vaccera), Helwan- Giza, Egypt, and allocated to plastic cages covered with metal grids and allowed to acclimate for 10 days in the animal facility conditions before being divided into groups. For experimentation they were divided into 7 groups as follows: Group 1 (G1) (8 rats): Animals of this group received no treatment and served as a control group. Group 2 (G2) (10 rats): Each rat was orally administrated with a gavage tube extract of Salix mucronata daily for 8 weeks (150mg/kg). Group 3 (G3) (10 rats): Injected by Ibuprofen (IBP) only dissolved in sterile saline intraprotenial (I.P.) daily for 8 weeks (40mg/kg). Group 4 (G4) (10 rats): Administrated by Acetylsalicylate (ASA) only (300mg/kg) daily for 8 weeks to induce liver fibrosis. Group 5 (G5) (10 rats): Administrated first with Acetylsalicylate (ASA) and at the same time injected with Ibuprofen (IBP) to investigate the effect of Ibuprofen on the infected rats. Group 6 (G6) (10 rats): Administrated first with Acetylsalicylate and simultaneously each rat was given an oral extract of Salix mucronata to investigate the effect of the extract on the infected rats. Group 7 (G7) (10 rats) was Administrated first with Acetylsalicylate (ASA) and at the same time treated with a combination of both extract and Ibuprofen. Results: Changes in CAT, GSH, MDA, hydrogen peroxide, and nitric oxide Rats injected with ASA (G4), and rats injected with ibuprofen (G3) showed a significant decrease in GSH and CAT and a significant increase in MDA, hydrogen peroxide, and nitric oxide levels if compared with G1. Treatment with extract and ibuprofen (G7) showed close levels of CAT, GSH, MDA, hydrogen peroxide, and NO to G1. Changes in AFP as a tumor marker, IL-6, TNF-alpha, and 5 –Nucleotidase. Rats injected with ASA (G4) and rats injected with ibuprofen (G3) showed a significant increase in AFP, IL-6, TNF-a, and 5 -Nucleotidase levels if compared with G1 (control). While their levels exhibited a significant decrease in rats treated with extract and ibuprofen (G7). Changes in COX-1 and COX-2; In rats injected with only ibuprofen (G3) and rats injected with ASA (G4) exhibited a significant decrease in COX-1 and COX-2 concentration if compared with G1 (control). By treatment with extract and ibuprofen (G7), the concentration of COX-1 and COX-2 increased returning to the normal ranges of close to control.