ABSTRACT
Comparative systemic and topical toxicity in male rats treated on the dorsal skin for 14 consecutive days with a volume of 0.15 g/100 g (body weight) of 0.1% hydrocortisone 17-butyrate 21-propionate (HBP) ointment, 0.05% clobetasol propionate (CP) ointment, 0.1% predonisolone 17-valerate 21-acetate (PVA) ointment and 0.1% diflucortolone valerate (DV) ointment was studied. In all the treated groups body weight gain was suppressed, serum concentration of total cholesterol and triglycerides increased and the lymphatic tissues and skin were atrophic. The DV and CP groups had adrenal atrophy and renal lesions, and the DV group also had gastric and hepatic lesions. The systemic effect of HBP ointment was weaker than that of the other drugs (DV greater than CP much greater than PVA greater than HBP). All the drugs significantly reduced the skin fold thickness in treated areas throughout the application period. The dermal atrophic effect of HBP ointment was also relatively weaker than that of the other drugs. From the above evidence, it was concluded that HBP ointment was less toxic than the other topical corticosteroids.
Subject(s)
Anti-Inflammatory Agents/toxicity , Hydrocortisone/analogs & derivatives , Administration, Topical , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/analogs & derivatives , Clobetasol/administration & dosage , Clobetasol/analogs & derivatives , Clobetasol/toxicity , Diflucortolone/administration & dosage , Diflucortolone/analogs & derivatives , Diflucortolone/toxicity , Hydrocortisone/administration & dosage , Hydrocortisone/toxicity , Male , Ointments , Prednisolone/analogs & derivatives , Rats , Rats, Inbred Strains , Skin/drug effectsABSTRACT
Anti-inflammatory activities of prednisolone 17-valerate 21-acetate(PVA) were studied in rats and guinea pigs and results compared with data on topical steroids, such as betamethasone 17-valerate(BV) and hydrocortisone 17-butyrate(HB). PVA given subcutaneously inhibited dose-dependently carrageenin- and kaolin-induced edema. These anti-inflammatory activities of PVA were the weakest among the steroids tested. A local administration of PVA into the site of inflammation, however, had the same or more potent activities than BV and HB in carrageenin-induced edema and paper disk granuloma. Topical application of PVA ointment in carrageenin-induced edema exhibited an inhibitory effect which was dependent on the concentrations (0.1-1.0%). The anti-inflammatory activity of 0.3% PVA ointment was equivalent to that of 0.12% BV ointment. For the other experimental models, i.e. exuberant granulation, croton oil-induced ear edema, passive cutaneous anaphylaxis and tuberculin-induced delayed type hypersensitivity, the activity of 0.3% PVA ointment was the same or somewhat more potent than 0.12% BV and 0.1% HB ointments. The thymolytic activity of PVA ointment in the exuberant granulation model was similar to the activity seen with HB ointment and weaker than of BV ointment. Thus, the anti-inflammatory activities of PVA were equivalent to or more potent than those of BV and HB, and with topical application, the systemic effect of PVA was weaker than the other steroids examined.
Subject(s)
Anti-Inflammatory Agents , Anti-Inflammatory Agents/analogs & derivatives , Administration, Topical , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Edema/drug therapy , Electrolytes/urine , Female , Gonadal Steroid Hormones/antagonists & inhibitors , Granuloma/drug therapy , Guinea Pigs , Hypersensitivity, Delayed/drug therapy , Liver Glycogen/metabolism , Male , Mice , Passive Cutaneous Anaphylaxis/drug effects , Prednisolone/analogs & derivatives , Rabbits , RatsABSTRACT
The in vivo effects of prednisolone 17-valerate 21-acetate (PVA), an anti-inflammatory glucocorticoid on several immunological responses in mice were investigated in comparison with hydrocortisone 17-butyrate (HB) and betamethasone 17-valerate (BV), when given subcutaneously. PVA reduced the spleen weight, the number of splenic nucleated cells, the formation of hemolytic plaque forming cells (PFC), delayed type footpad reaction and the responsiveness of splenic lymphocytes to concanavalin A. These suppressive effects were almost the same as those seen with HB and weaker than those of BV. However, the responsiveness of splenic cells to lipopolysaccharide and circulating IgM antibody response to sheep red blood cells were suppressed by a smaller dose of PVA than that of HB. PVA had no effect on the responsiveness to phytohemagglutinin-P, whereas HB and BV enhanced the phytohemagglutinin-P responsiveness. The suppressive effect of PVA on the host defense to experimental infection with Escherichia coli was weaker than those of HB and BV. From these results, PVA appears to be similar to other glucocorticoids in that it exerts complicated effects on several immunological responses in mice.
