Hepatic fibrosis and its end point; cirrhosis, are the major cause of liver failure and death in patients with chronic liver disease. Therefore, the need for an effective treatment is evident. This study was designed to assess the potential effects of aqueous extract of date fruits, either flesh (DFE) or pits (DPE), on oxidative DNA damage and liver inflammation induced by carbon tetrachloride (CCl 4) and whether they are related to inhibition of nuclear factor-κB pathway. In addition, the fibrolytic potential was evaluated via measuring matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases −1 and −2.
Rats were divided into the following groups: normal control, model control (CCl 4 only), CCl 4 + DFE, CCl 4 + DPE and CCl 4 + coffee. Coffee was used as a positive control. Fibrosis was induced by chronic administration of CCl 4 (0.4 ml/kg) 3× a week for 8 weeks, and rats were treated with 6 ml/kg/day of DFE or DPE for 8 weeks. Liver homogenate was prepared for evaluation of oxidative stress, DNA damage, inflammatory and fibrolytic markers. Data are analyzed using one-way analysis of variance followed by a Tukey-Kramer post hoc test.
Both DFE and DPE significantly attenuated CCl 4-induced oxidative damage as indicated by reducing lipid, protein and DNA oxidation in addition to increasing the levels of hepatic catalase activity. Both extracts blocked the accumulation of collagen I in the liver and ameliorated the increased expression of collagen III and α-smooth muscle actin suggesting suppression of profibrotic response induced by CCl 4. DFE and DPE also upregulated the expression of heme oxygenase-1 and attenuated the nuclear factor-κB activation and cycloxygenase-2 expression reflecting their anti-inflammatory potential. Additionally, both flesh and pits extracts attenuated the increase in the tissue inhibitor of metalloproteinases −1 and −2 suggesting their fibrolytic activity.