Effects of N-Acetyl Cysteine on the Expression of Matrix Metalloproteinases 2 and 9 in the Lung Tissue of Rats Exposed to Cadmium

 Cadmium (Cd) is a natural and heavy metal, which is widely widespread in the atmosphere. Studies report that environmental exposure to Cd increases the risk of various disorders, such as pulmonary diseases. On the other hand, Cd increases the reactive oxygen species (ROS), which interacts with biomolecules (e.g. DNA, proteins, and lipids) and causes severe damages. In addition, Cd may play a role in the dysregulation of the expression and activity of matrix metalloproteinases (MMPs). Since ROS and oxidative stress are likely the main reasons for MMPs dysregulation, antioxidants therapy may protect tissues against Cd-induced damages. Furthermore, N-acetylcysteine (NAC) protects cells against oxidative stress and toxic compounds.

 This study aimed to investigate the effect of cadmium (Cd) on the matrix metalloproteinases (MMPs) -2 and -9 expression in the lung, and the role of N-acetylcysteine (NAC) in preserving the lung cells against Cd toxicity.

 The rats were randomly divided into five groups of G1 (control), G2 (single dose of Cd), G3 (continuous dose of Cd), G4 (single dose of Cd+NAC), and G5 (continuous dose of Cd+NAC). The level of Cd in the blood and lung tissue was measured by atomic absorption spectroscopy. Moreover, the expression of MMP2 and MMP9 genes was evaluated using RT-PCR.

 Single and continuous exposure to Cd caused a significant increase in serum and the lung tissue of Cd in G2 (0.23±0.04 mg/L and 0.35±0.047 μg/g tissue) and G3 (0.50±0.068 mg/L and 0.81±0.063 μg/g tissue) groups, compared to other groups (P<0.001). The NAC supplementation significantly decreased Cd levels in the serum and lung tissue samples of rats exposed to single or continuous Cd (P<0.001). Furthermore, exposure to a single and continuous dose of Cd caused a significant increase in the MMP2 expression by 3.24-fold (P=0.003) and 11.9-fold (P<0.001), respectively. Additionally, treatment with single and continuous dose treatment of Cd led to a significant increase in the MMP9 expression by 3.20-fold (P=0.004) and 7.54-fold (P<0.001), respectively. The NAC treatments decreased the expression of MMP2 and MMP9 in the lung of rats exposed to a single or continuous dose of Cd.

 The Cd exposure was strongly associated with the accumulation of Cd and overexpression of MMP2 and MMP9 in the lung tissue. Moreover, the NAC can protect the lungs against Cd toxicity by decreasing Cd and down-regulating MMPs.