The effects of N-acetyl cysteine on the expression of MMP9 and TIMP2 genes in the liver tissue of cadmium exposed rats

Abstract

Introduction: The aim of this experimental study was to investigate the effect of cadmium (Cd) on the expression of matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 2 (TIMP2) genes and to investigate the protective role of N-acetylcysteine (NAC) on cadmium toxicity in the liver tissue of rats.
Materials & Methods: In this study, male Wistar rats were randomly divided into 5 groups: control (G1), single dose of cadmium (80 mg/kg) (G2), continuous dose of cadmium (2.5 mg/kg) (G3), Single dose of cadmium (80 mg / kg) and continuous dose of NAC (50 mg/kg) (G4) and continuous dose of cadmium (2.5 mg/kg) and continuous dose of NAC (50 mg/kg) (G5). Hematoxylin and eosin (H&E) staining was used to study histopathological changes. Cadmium concentration was measured by graphite furnace spectroscopy in the liver samples. The expression of MMP9 and TIMP2 genes was evaluated using RT-PCR.
Results: Cadmium exposure, especially at continuous dose, was associated with severe tissue damage and increased inflammatory cells in the liver. The mean tissue of cadmium concentration was significantly increased by 27% (P<0.05) in the G2 group and 60% (P<0.01) in G3 group. NAC treatment in G4 group (P<0.01) and G5 group (P<0.01) significantly reduced the tissue concentration of cadmium. Cadmium also increased the expression of MMP9 gene (P<0.001) and TIMP2 gene (P<0.01) in G2 and G3 groups. NAC treatment significantly reversed these effects.
Conclusion: Results suggested that NAC protects liver cells by decreasing the accumulation of cadmium and reducing the expression of TIMP2 and MMP9 genes.