European Journal of Biomedical and Pharmaceutical Sciences

SULFASALAZINE AND MESALAZINE MODULATES LIGHT EXPRESSION IN EXPERIMENTAL HEPATIC FIBROSIS

Ahmed I Abulsoud* and Ahmed M Mansour

ABSTRACT

Background: LIGHT (TNFSF14), a tumor necrosis factor superfamily member expressed by activated T cells, binds to HVEM which is constitutively expressed by T cells and stimulates T cell activation in a CD28- independent manner. Given interest to proposed LIGHT fibrinogenic role in hepatocytes, we examined the role of LIGHT in experimental hepatic fibrosis and the impact of sulfasalazine and mesalazine on its expression in hepatocytes. Objective: Characterization of LIGHT expression pattern in in CCl4 induced hepatic fibrosis model with investigation of possible modulatory effects of sulfasalazine and mesalazine. Methods: Thirty six adult male rats weighing 250–300 g were used. Animals were randomly divided into six groups 6 animals each: control group, 6 weeks group, DMSO group, sulfasalazine group, mesalazine group and 11 weeks group. All studied groups except controls were injected with CCl4. Tissue and serum samples obtained from all groups of rats were taken followed by determination of enzyme levels (AST, ALT, and ALP), tissue oxidative stress markers (SOD and MAD) and histopathological analysis. LIGHT expression examined against control group and positive control groups by immunofluorescence analysis. Results: Quantitative analysis of immunofluorescence staining expressed as fluorescence intensity revealed that sulfasalazine decreased LIGHT expression by about 73% and mesalazine by about 57% with respect to that of CCl4 treated group. Sulfasalazine concomitantly with CCl4 significantly decreased ALT from CCl4 alone or with DMSO groups but failed to retain it as the control, nevertheless AST and ALP did not significantly changed. Combination of sulfasalazine and CCl4 increased MDA content to 23.4±1.17 compared to DMSO group (19.2±1.72) while mesalazine showed the minimal increase in MDA tissue content (7.53±0.71) compared which control group (4.36±0.31 nmol/g) and remarkably was significantly different when compared with 6 weeks CCl4 treated group (19.7±1.52). SOD activity of hepatic tissue was 524±41.6 U/mg tissue. This content was significantly decreased in other groups to be 264±14.1 for 6 weeks group, 357±31.3 for DMSO, 264±14.1 for 11 weeks group, 283±27.8 for sulfasalazine group and 226±16.8 for mesalazine group. Conclusion: Both sulfasalazine and mesalazine modulates expression of hepatocytes LIGHT, however a dominance of sulfasalazine were detected. Hereafter both can protect against hepatic fibrosis.

Keywords: Sulfasalazine, Mesalazine, LIGHT, Hepatic Fibrosis.