High-fat Western diet alters crystalline silica-induced airway epithelium ion transport but not airway smooth muscle reactivity

Silicosis is an irreversible occupational lung disease resulting from crystalline silica inhalation. Previously, we discovered that Western diet (HFWD)-consumption increases susceptibility to silica-induced pulmonary inflammation and fibrosis. This study investigated the potential of HFWD to alter silica-induced effects on airway epithelial ion transport and smooth muscle reactivity.

Six-week-old male F344 rats were fed a HFWD or standard rat chow (STD) and exposed to silica (Min-U-Sil 5^®, 15 mg/m³, 6 h/day, 5 days/week, for 39 d) or filtered air. Experimental endpoints were measured at 0, 4, and 8 weeks post-exposure. Transepithelial potential difference (V_t), short-circuit current (I_SC) and transepithelial resistance (R_t) were measured in tracheal segments and ion transport inhibitors [amiloride, Na⁺ channel blocker; NPPB; Clˉ channel blocker; ouabain, Na⁺, K⁺-pump blocker] identified changes in ion transport pathways. Changes in airway smooth muscle reactivity to methacholine (MCh) were investigated in the isolated perfused trachea preparation.

Silica reduced basal I_SC at 4 weeks and HFWD reduced the I_SC response to amiloride at 0 week compared to air control. HFWD + silica exposure induced changes in ion transport 0 and 4 weeks after treatment compared to silica or HFWD treatments alone. No effects on airway smooth muscle reactivity to MCh were observed.