Biologic role of fetal lung fibroblast triglycerides as antioxidants

The pulmonary response to hyperoxia is highly variable, depending on such s eemingly disparate biologic factors as gestational age, sex, hormonal milie u, and nutritional status. Descriptively, the magnitude and direction of th ese biologic differences in response to hyperoxia correlate with the trigly ceride content of developing fetal rat lung fibroblasts (FRLFs). Mechanisti cally, these same factors affect the triglyceride content of FRLFs, e.g. d 21 FRLFs contain more triglyceride than d 18 FRLFs; female FRLFs contain mo re triglyceride than male FRLFs (d 20); dexamethasone increases FRLF trigly ceride content, dihydrotestosterone decreases it; nutritionally, exposure o f FRLFs to graded amounts of serum triglyceride (0%, 2%, 10%, 20%) results in increased intracellular FRLF triglyceride content. To test the hypothesi s that these biologic differences in intracellular triglyceride content may account for differences in the cytoprotection of lung fibroblasts against oxidant injury, fibroblast cultures representing each of these biologic gro ups were challenged with graded doses of the reactive oxygen species hydrog en peroxide (0.1-1.0 mM for 5 min). The number of surviving cells and their antioxidant status, as measured by lipid peroxidation and glutathione cont ent of the surviving cells, were determined. We found that in response to h ydrogen peroxide 1) d 21 FRLFs were more resistant than d 18 FRLFs; 2) fema le FRLFs were more resistant than male FRLFs; 3) dexamethasone-treated FRLF s were more resistant than dihydrotestosterone treated fibroblasts; 4) fibr oblasts fed increasing amounts of serum triglycerides were increasingly res istant to hydrogen peroxide; 5) cell survival in different serum triglyceri de- and hormone-treated groups was not related to the antioxidant status as measured by glutathione content. These data are consistent with the hypoth esized role of FRLF triglycerides as antioxidants.