Propacetamol hydrochloride

BALB/cByJNarl (six-week-old male, 20-22 g, acute liver injury induced by propacetamol injection)^[2]

600 mg/kg (acute liver injury induction); 1200 mg/kg (lethal model)

i.p.; single injection

Induced significant acute liver injury, characterized by dark red discoloration of liver tissue, marked elevations in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, severe histopathological liver damage (cell vacuolization, membrane loss, nuclear disappearance, bleeding, and elevated histopathological scores), reduced hepatic glutathione (GSH) levels, increased thiobarbituric acid reactive substances (TBARS) and 3-nitrotyrosine (3-NT) levels, suppressed superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, increased serum tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels, increased hepatic Bax expression and Bax/Bcl-2 ratio at 6 h post-injection, increased cleaved caspase-3 expression at 12 h post-injection, 83.00 ± 2.89% TUNEL-positive liver area at 18 h post-injection, increased hepatic cytochrome P450 2E1 (CYP2E1) expression, reduced UDP-glucuronosyltransferase family 1 member A1 (UGT1A1) expression, increased nuclear nuclear factor erythroid 2-related factor 2 (Nrf2) levels at 6 h post-injection, reduced Nrf2 and glutamate cysteine ligase catalytic subunit (GCLC) levels at 18 h post-injection, increased heme oxygenase 1 (HO-1) levels at 18 h post-injection, increased phosphorylated c-jun-N-terminal kinase (p-JNK)/JNK and phosphorylated extracellular signal-regulated kinase (p-ERK)/ERK ratios at 6 h post-injection, and increased hepatic receptor-interacting serine/threonine-protein kinase 1 (RIP1) expression at 6 h post-injection.\nCaused 100% mortality of all tested mice within 14 h post-injection without post-treatment.

BALB/cByJNarl (male, 5 weeks old, 20-22 g, acute liver injury induced by intraperitoneal propacetamol injection)^[3]

1200 mg/kg; 1400 mg/kg

i.p.; single dose

Resulted in 10% survival at 168 h post-injection (1200 mg/kg).\nResulted in 0% survival at 168 h post-injection (1400 mg/kg).

C57BL/6JNarl (male, 5 weeks old, 20-22 g, acute liver injury induced by intraperitoneal propacetamol injection)^[3]

1200 mg/kg; 1400 mg/kg; 1600 mg/kg; 1800 mg/kg

i.p.; single dose

Resulted in 50% survival at 168 h post-injection (1200 mg/kg).\nResulted in 40% survival at 168 h post-injection (1400 mg/kg).\nResulted in 0% survival at 168 h post-injection (1600 mg/kg).\nResulted in 0% survival at 168 h post-injection (1800 mg/kg).

Wistar (male, 240-270 g, ASA-induced gastric ulceration)^[5]

125 mg/kg; 250 mg/kg; 500 mg/kg

i.g.; single dose; 30 min before ASA

Reduced ASA-induced gastric ulcer area by 22.0% (125 mg/kg), 38.5% (250 mg/kg), and 52.9% (500 mg/kg).\nReduced ASA-elevated gastric mucosal MDA levels by 48.4% (125 mg/kg), 56.3% (250 mg/kg), and 66.9% (500 mg/kg).\nElevated gastric mucosal UA levels above control values and significantly higher than the ASA-only group at 250 mg/kg and 500 mg/kg.\nDecreased gastric mucosal GSH and GSSG levels compared to the ASA-only group but remained significantly higher than control values.\nCaused gastric mucosa to appear almost normal, with only occasional bending of superficial epithelium and focal desquamation observed.\nReduced plasma MDA levels by a slight, non-significant 1.5% at 500 mg/kg compared to the ASA-only group.\nElevated plasma UA levels above control values, increasing by 19.8% (250 mg/kg) and 26.7% (500 mg/kg) compared to the ASA-only group.