Prozime-10 (P-10), a proteolytic enzyme extracted from cultured broth of Aspergillus melleus, was injected intravenously into rats in dosages of 1-10 mg/kg and was found to alleviate carrageenin edema. Thermal denaturation diminished not only the proteolytic activity but also the antiedematous effect. Carrageenin-induced granuloma pouches in rats were reduced by P-10 in a dose-dependent manner (1–5 mg/kg). With P-10 (5 mg/kg i.v.), adjuvant arthritis was inhibited by 62% in the primary phase and by 57% in the secondary phase. Serum concentration of immunoprecipitable P-10 reached 100 mg/l within 30 min after the intraduodenal administration of P-10 (200 mg/kg) and was concomitant with a 3-fold increase in the blood esterolytic activity. When P-10 was injected (5 mg/kg i.v.) into rats, the plasma corticosterone level increased to a maximum of 4 times the preinjection level. These observations indicate that: (a) P-10 can be absorbed from the gut in sufficient quantities to bring about anti-inflammatory activity, and (b) the anti-inflammatory activity of P-10 can be related, in part, to the ability of P-10 to affect the release of glucocorticoids.
When Prozime-10 (P-10), a protease extracted from cultured broth of Aspergillus melleus, was injected intravenously into anesthetized dogs, plasma ACTH was increased with a latency of 30 min, and this was followed by remarkable elevation of plasma cortisol in many instances. A similar increase in plasma cortisol was elicited after trypsin and α-chymotrypsin were injected. Plasma histamine was raised promptly prior to an increase in plasma ACTH after P-10 in every case. However, in certain cases, changes in cortisol occurred simultaneously with ACTH after P-10. Such a rapid elevation of cortisol can be explained, partly, by direct stimulation of the adrenal cortex by histamine.
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