IDN-7314

Sprague-Dawley (female, 150-200 g, chemical-induced hepatitis model)^[1]

10 mg/kg (6-hour observation group); 10 mg/kg (24-hour two-dose group); 10 mg/kg (24-hour pretreatment group)

i.p.; two doses at 3 and 4.5 hours post-galactosamine (6-hour group); two doses at 3 and 6 hours post-galactosamine (24-hour two-dose group); three doses 30 minutes pre-galactosamine, 3 and 6 hours post-galactosamine (24-hour pretreatment group)

Reduced the percentage of apoptotic hepatocytes by 76% (from 5.0 ± 0.34% to baseline-like levels) at 6 hours post-galactosamine.
Reduced hepatic and plasma caspase-3 activities to control levels at 6 hours post-galactosamine.
Prevented procaspase-3 processing to its active fragment at 6 hours post-galactosamine.
Did not reduce plasma ALT activities at 6 hours post-galactosamine.
Had no significant effect on oncotic cell counts at 6 hours post-galactosamine.
Reduced plasma ALT levels by 57% (p < 0.05) at 24 hours post-galactosamine (two-dose schedule).
Reduced hepatocellular oncosis by 24% (p > 0.05) at 24 hours post-galactosamine (two-dose schedule).
Reduced hepatic and plasma caspase-3 activities to baseline at 24 hours post-galactosamine (two-dose schedule).
Reduced the percentage of apoptotic hepatocytes by 71% (from 7.3 ± 1.1% to 2.1 ± 0.4%) at 24 hours post-galactosamine (three-dose pretreatment schedule).
Had no significant effect on plasma ALT activities or oncotic cell counts at 24 hours post-galactosamine (three-dose pretreatment schedule).

Sprague-Dawley (female, 150-200 g, chemical-induced hepatitis model)^[1]

10 mg/kg

i.p.; two doses at 3 and 4.5 hours post-galactosamine/endotoxin injection

Reduced hepatic caspase-3 activities from 194 ± 33 ΔF/min/mg protein to baseline 16 ± 5 ΔF/min/mg protein.
Reduced plasma caspase-3 activities from 12.9 ± 1.5 ΔF/min/mg protein to baseline 0.2 ± 0.2 ΔF/min/mg protein.
Reduced the percentage of apoptotic hepatocytes by 80% (from 7.33 ± 0.32% to 1.50 ± 0.29%).
Reduced plasma ALT activities by 50% (from 708 ± 54 IU/L to 359 ± 34 IU/L).
Reduced the percentage of oncotic hepatocytes by 33% (from 2.35 ± 0.22% to 1.58 ± 0.13%).

C57BL/6J (male, 8-12 weeks old, Fas-induced apoptotic liver injury model)^[2]

3 mg/kg

i.p.; single dose (administered 1 hour after Jo2 injection)

Attenuated Jo2-induced hepatic cleaved caspase-3 levels.
Abolished Jo2-induced increases in plasma alanine aminotransferase (ALT) activity.
Eliminated Jo2-induced hepatic sinusoidal congestion/hemorrhage.
Completely prevented Jo2-induced increases in plasma TF-positive microvesicle levels.
Blocked Jo2-induced increases in plasma thrombin-antithrombin (TAT) levels.
Attenuated Jo2-induced hepatic fibrin(ogen) β chain accumulation.
Abolished Jo2-induced hepatic cleaved caspase-3 staining and dramatically reduced hepatic fibrin(ogen) deposition.