الفهرس 
List of abbreviationsOnly 14 pages are availabe for public view
 |  | from | 129 |  |  |
| | | from | 129 | | |
Abstract
Approximately 10% of world population is affected with liver diseases. Both acetaminophen (APAP) overdose and the bacterial component lipopolysaccharide (LPS) account for many cases of acute liver injury. In the present study, the possible hepatoprotective effect of the selective non-peptide CXCR2 chemokine antagonist SB-332235 and Zoledronic acid on acute liver injury induced by either APAP in mice or LPS in rats was investigated. Model : acute liver injury induced by APAP in mice (500 mg/ kg): We found that, pre-treatment with ZA (0.1 mg/kg) prevented APAP-induced liver injury in mice manifested by significantly inhibiting APAP-induced elevations in serum alanine aminotransferase by (100%), aspartate aminotransferase by (33%), alkaline phosphatase ALP by (53%), total bilirubin by (300%) and γ-glutamyl transferase by (50%), and hepatic malondialdehyde contents by (80%). In addition, it significantly prevented APAP-induced reduction in hepatic reduced glutathione by (330%) and superoxide dismutase by (93%). ZA effectively preserved tissue morphology as evidenced by histological evaluation, while pre-treatment with SB332235 (3.3 mg/kg) didn’t inhibit the injury. Model 2 : acute liver injury induced by LPS in rats (10 mg/kg): it was shown that, SB332235 pretreatment (3.5 mg/kg) prevented LPS-induced liver injury manifested by significantly inhibiting LPS-induced elevations in serum alanine aminotransferase by (86%), aspartate aminotransferase by (44%), alkaline phosphatase ALP by (54%), total bilirubin by (78%) and γ-glutamyl transferase by (53%), tumor necrosis factor-α levels by (656%) and hepatic malondialdehyde contents by (57%). Conversely, the LPS-induced elevation in interleukin-10 was not significantly affected by SB332235 administration. In addition, SB332235 significantly prevented LPS-induced reduction in hepatic reduced glutathione by (181%) and superoxide dismutase by (27%). SB33235 effectively preserved tissue morphology as evidenced by histological evaluation, while pre-treatment with ZA (0.7 mg/kg) didn’t inhibit the injury.