Some Anti-Inflammatory Properties of Ascorbic Acid

Abstract

Vascular and cell membrane permeability increases, the immune (allergic) response, and lysosomal hydrolase activity are interrelated in the inflammatory process. Ascorbic acid has been shown to play a stabilizing role in several of these processes indirectly in scorbutic animals. Ascorbic acid deficiency leads to separation of the cells in the vascular endothelium (1). A similar effect has been observed after histamine injection ( 2 ) . The evidence for ascorbate stabilization of cellular membranes is not well documented (3). The anti-allergic effect of ascorbic acid has been demonstrated through its ability to reduce anaphylaxis in the guinea pig (4), mouse ( 5 ) , and rat ( 6 ) ; but not in the dog ( 7 ) . We have shown previously that ascorbic acid can inhibit lysosomal P-glucuronidase (8). These results led us to investigate the effect of ascorbic acid in several animal models of inflammation. This report compares the inhibitory actions of ascorbic acid, aspirin, and phenylbutazone against rat liver lysosomal P-glucuronidase (in vitro), UV erythema in guinea pigs, carrageenan edema in rats, adjuvant arthritis and peritonitis-polyarthritis in rats.Materials and Methods. Animals used in these studies were (1) male, Cox/Holtzman rats for lysosomal P-glucuronidase and PPA, (2) female, Harlan/Holtzman rats for carrageenan edema and adjuvant arthritis, and (3) female albino guinea pigs for UV erythema. L-Ascorbic acid (Eastman), aspirin, and phenylbutazone (Geigy) were made up in stock solutions 2 0 x final concentration in ethanol/isotonic saline ( 1 / 1 ) for in vitro studies and five-fold concentration in carboxymethylcellulose for animal studies. Lysosomes were prepared by the method of deDuve et al. (9). The lysosomal pellets from five grams of rat liver were suspended in 200 ml of Mg-free Krebs-Ringer-Phosphate buffer, pH 7.4. Fifty p1 of stock solution of drug was added to 1 ml of lysosomal suspension. Control tubes contained 1 ml of lysosomal suspension and 50 pl of ethanol/saline. The tubes were incubated for 60 min at 37'. Then, 250 p1 of 5 mM p henolph t hale in-p-glucur onide ( sodium salt ) (Sigma) in 0.5 M acetate buffer, pH 5.0, was added to each tube. Incubation was continued for an additional 10 min. The enzyme reaction was stopped by the addition of 2.0 ml of 0.4 M glycine buffer, pH 10.7, containing 0.2 5 % sodium dodecyl sulfate to clear the suspension. Phenolphthalein was determined with a Zeiss PMQ I1 spectrophotometer at 560 nm.UV erythema was induced on guinea pigs by a modification of the method of Winder et al. ( 10). A Hanovia lamp (Kromayer model 10) was placed in contact with the skin on the back of a guinea pig for seven seconds. The animals were dosed Po 15 min before UV exposure. The erythemas were examined at 1 hr then half hour intervals until two and one-half hours after irradiation. The severity of the burn was rated 0-3. The rating was multiplied by 4 at 1 hr, 3, 2, 1 for each of the successive intervals. Control irradiated animals rated 120 by this technique.Edema was produced ...

Nature of intramolecular interactions of vitamin C in view of interacting quantum atoms: the role of hydrogen bond cooperativity on geometry

“…Vitamin C (L-ascorbic acid, AA) is a vital compound due to its various functions in organisms. Anti-scurvy, 1 anti-tumor, 2 antiinflammatory, 3 protective effects on skin atrophy, 4 reduced risk of cataract, 5 and acting as a cofactor in the enzymatic reactions of collagen synthesis 6 are a few examples of vitamin C's properties in biosystems.…”