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In the present study we investigated the relationship between the in vivo effects and the in vitro effects of serine and thiol proteinase inhibitors. Each one of the inhibitors, leupeptin, dansyl-L-leucyl-L-argininal (Dan-Leu-Argal), pyroglutamyl-L-leucyl-L-argininal (Pyr-Leu-Argal), E-64C or EP-459 was given intraperitoneally to mice for 8 consecutive days and various enzymatic activities were tested in 6 organs: forelimb muscle, hindlimb muscle, heart, spleen, liver and kidney. A multivariate analysis clearly differentiated the effects of leupeptin from those of its two analogues (Dan-Leu-Argal and Pyr-Leu-Argal), while the two analogues showed close relations with each other as to their in vivo effects. E-64C and EP-459 also showed resemblance of in vivo effects between them, but the effects of these two agents were clearly differentiated from those of leupeptin and its two analogues. This kind of study seems important to assess the in vivo effects of physiologically active substances including enzyme inhibitors.

Relation between in vivo effects and in vitro effects of serine and thiol proteinase inhibitors.