The neuroprotective effect of N-acetylcysteine by regulating inflammation and expression ‎of TNF-α and ERK gene expression in the rats exposed to different doses of cadmium.

BACKGROUND

Cadmium is known to disrupt cellular proliferation through unregulated cell division. This process leads to activation of TNF-α cytokines, resulting in cellular damage and increased inflammation in cells, including brain cells. This study investigates the regulation of TNF-α and ERK gene expression patterns mediated by N-acetylcysteine in response to cadmium exposure in Wistar rats.‎.

METHODS AND RESULTS

Wistar rats (n = 37) were divided into five groups: control (G1), acute cadmium exposure (G2), chronic cadmium exposure (G3), acute cadmium with N-acetylcysteine (G4), and chronic cadmium with N-acetylcysteine (G5). Brain tissue sections were prepared and stained with H&E. Then, the G-FAP was measured ‎using immunohistochemistry. ELISA was employed to detect IL-1β and IL-10 levels. TNF and ERK gene expression ‎was assessed using RT-PCR. Histopathological examination revealed increased glial inflammatory cells in groups G2 and G3. N-acetylcysteine reduced inflammatory cell infiltration, and G-FAP staining confirmed decreased astrocytic accumulation in G5. IL-1β levels significantly decreased in G5 after N-acetylcysteine therapy, while IL-10 levels increased after treatment but subsequently declined due to chronic cadmium exposure. TNF gene expression increased in G2 and G3 but decreased significantly in G5, demonstrating N-acetylcysteine's suppressive effect. Furthermore, ERK gene expression significantly increased in G2 and ‎G3. However, there were notable decreases in both G4 and G5 compared to cadmium-exposed controls.

CONCLUSION

This study demonstrated that N-acetylcysteine mitigates oxidative stress-induced tissue damage, prevents apoptosis, and exhibits anti-inflammatory properties by downregulating TNF-α and upregulating ERK gene expression.