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Changes in Response to Ascorbic Acid Administered Orally to Rat Pups: Lung Collagen, Elastin and Protein Synthesis¹

James W. Critchfield^*, Michael Dubick^*, Jerold Last, Carroll E. Cross and Robert B. Rucker^2,*

^* Department of Nutrition University of California Primate Center Pulmonary Medicine, University of California, Davis, CA 95616

Rat pups were supplemented orally with high doses of L-ascorbic acid (AA) or D-isoascorbic acid (IA) throughout suckling. The regulation of AA in the lung and its relationship to collagen and elastin deposition were examined. Based on known resposes of smooth muscle cells and fibroblasts in culture to high concentrations of AA, it was hypothesized that a markedly elevated intake of AA should increase net collagen deposition, but decrease net elastin deposition in the neonatal rat lung. In two experiments, groups of rat pups were gavaged daily with AA (in saline), in amounts corresponding to 0.1, 1 or 2% of the total consumed milk solids. As controls, pups were gavaged with IA (2% of the milk solids) or saline. The treatments were initiated 2 d postpartum and continued for 19 or 23 d. Compared to the salinegavaged pups little change was observed in body or lung weights in AA- and IA-treated pups. AA and IA were elevated (twofold) in serum and lung at d 11, but not at d 25. Urinary excretion represented a major route for the elimination of excess AA and IA. With respect to collagen and elastin accumulation, only elastin consistently was altered (10–20% decrease) in groups supplemented with AA or IA at the termination of experiments. The rodent appears to defend against elevation of AA concentration in the lung. Consequently, the putative effects of AA on the net deposition of lung collagen and elastin in vivo are less obvious than effects reported by others from in vitro studies.

KEY WORDS: • ascorbic acid • lung • elastin

¹ This work was supported in part by National Heart, Lung and Blood Institute of the National Institutes of Health grants HL15965 and HL17957.

² To whom reprint requests should be directed.

Manuscript received 10 February 1984.