Background: acetaminophen (APAP) is an important drug that cause nephrotoxicity and hepatic
toxicity in high dose. Glutathione S-transferase A1 (GSTA1) is a marker that used to early diagnosis 
of this toxicity in rats. Dexmedetomidine (DEX) is an antioxidant, so it play an important role in 
treatment of liver and renal affection caused by high dose of APAP. Methods: 100 rats divided into 5 
groups, group I received normal saline, group II received APAP, group III received APAP + NAC, 
group IV received APAP + DEX, and group V received APAP + NAC + DEX. Blood samples were 
drawn from group I after 24hours, from group II after 6, 8, 10 hours, from group II, III, IV, V after 24 
hours. By these samples we estimated Alanine Transferase (ALT), Aspartate transaminase (AST), 
serum urea, serum creatinine, Glutathione S-transferase A1 (GSTA1), Catalase enzyme (CAT),
Glutathione peroxidase (GSH-Px), Malondialdehyde (MDA). Liver and kidney of each rat were 
dissected for histopathology after scarification. Results: the levels of ALT, AST, urea, and creatinine 
were significantly increased in group of APAP, and significantly decreased in group APAP + NAC, 
and APAP + NAC + DEX. The levels of glutathione peroxidase, and catalase ( antioxidants) were 
significantly decreased in group of APAP, and significantly increased in group APAP + NAC, and 
group APAP + NAC + DEX. The levels of MDA that excreted due to lipid peroxidation were
significantly increased in group APAP. NAC alone or NAC + DEX induced a significant decrease in a 
level of MDA but DEX alone could not induce a statistically significant reduction in MDA level. In 
group of APAP, ALT and AST were statistically significant after 8 hours and 10 hours of giving 
APAP but GSTA1 started to be statistically significant after 6 hours. Conclusion: GSTA1 is 
considered a marker for early diagnosis of hepatic injury and renal affection of acute acetaminophen 
toxicity, also DEX had an important role in its treatment.