Residual oil fly ash inhalation in guinea pigs: Influence of absorbate andglutathione depletion

Inhaled urban particulate matter (PM) often contains metals that appear to contribute to its toxicity, These particles first make contact with a thin layer of epithelial lining fluid in the respiratory tract. Antioxidants pre sent in this fluid and in cells might be important susceptibility factors i n PM toxicity. We investigated the role of ascorbic acid (C) and glutathion e (GSH) as determinants of susceptibility to inhaled residual oil fly ash ( ROFA) in guinea pigs (male, Hartley). Guinea pigs mere divided into four gr oups, +C+GSH, +C-GSH, -C+GSH, and -C-GSH, and exposed to clean air or ROFA (< 2.5 micron diameter, 19-25 mg/m(3) nose-only for 2.0 h). C and/or GSH we re lowered by either feeding C-depleted diet (1 <mu>g C/kg diet, 2 weeks) a nd/or by ip injection of a mixture of buthionine-S,R-sulfosimine (2.7 mmol/ kg body weight) and diethylmaleate (1.2 mmol/kg, 2 h prior). Nasal lavage ( NL) and bronchoalveolar lavage (BAL) fluid and cells were. examined at 0 h and 24 h postexposure to ROFA, The C-deficient diet lowered C concentration s in BAL fluid and cells and in NL fluid by 90%, and the GSH-depletion regi men lowered both GSH and C in the BAL fluid and cells by 50%. ROFA depositi on was calculated at time 0 from lung Ni levels to be 46 mug/g wet lung. In unexposed animals, the combined deficiency of C and GSH modified the cellu lar composition of cells recovered in lavage fluid, i.e., the increased num ber of eosinophils and macrophages in BAL fluid. ROFA inhalation increased lung injury in the -C-GSH group only (evidenced by increased BAL protein, L DH and neutrophils, and decreased BAL macrophages). ROFA exposure decreased C in BAL, and NL at 0 h, and increased BAL C and GSH (2- to 4-fold above n ormal) at 24 h in nondepleted guinea pigs, but had no effect on C and GSH i n depleted guinea pigs, Combined deficiency of C and GSH resulted in the hi ghest macrophage and eosinophil counts of any group. GSH depletion was asso ciated with increased BAL protein and LDH, increased numbers of BAL macroph ages and eosinophils, and decreased rectal body temperatures. We conclude t hat combined deficiency of C and GSH increased susceptibility to inhaled RO FA; caused unusual BAL cellular changes; resulted in lower antioxidant conc entrations in BAL than were observed with single deficiencies. Antioxidant deficiency may explain increased susceptibility to PM in elderly or disease d populations and may have important implications for extrapolating animal toxicity data to humans.