Vrbova 2015 Abstract MiPschool London 2015

From Bioblast
Acetaminophen conjugate induces mitochondria-related oxidative impairment in HK-2 cells.


Vrbova M, Rousarova E, Capek J, Rousar T (2015)

Event: MiPschool London 2015

Acetaminophen (APAP) belongs to the most used analgetic and antipyretic drugs. APAP overdose causes liver injury and that is why it is the most frequent cause of acute liver injuries in the Western countries. In some cases, it is also associated with renal impairment occurring with frequency 1-2% of patients with acetaminophen overdose [1,2]. Acetaminophen is detoxified by three major pathways, glucuronidation, sulfation and oxidation by cytochrome P450. At therapeutic doses, a small portion of APAP dose is oxidized by cytochrome P450 to a reactive electrophilic molecule (NAPQI). After overdose, APAP is metabolized predominantly through the oxidation pathway and production of the oxidation product is enhanced. NAPQI is considered to be the toxic metabolite causing cell impairment [3]. However, based on our preliminary results, we postulated, that another metabolite could also cause toxicity.

Our study's aim was to characterize the toxicity of APAP metabolite in the human HK-2 cell line. We used a range of concentrations (10-5 mM) to examine the toxicity in cells. We evaluated the toxicity using the detection of mitochondrial dehydrogenase activity (WST-1 test), lactate dehydrogenase activity assay and detection of intracellular ROS production.

We observed moderate impairment of cells already after 3 h of treatment based on the finding of decreased mitochondrial dehydrogenase activity in all tested concentrations. After 24 hours, the results showed significant cellular impairment and increased ROS production at all tested concentrations.

In conclusion, we have proven our hypothesis that APAP metabolites ought to be also concerned in APAP toxicity. The toxic effect is presumably apparent as a decrease in mitochondrial dehydrogenase activity and induction of ROS production.

β€’ O2k-Network Lab: CZ Hradec Kralove Cervinkova Z, CZ Pardubice Rousar T


Organism: Human  Tissue;cell: Other cell lines 


1-Dept Biol Biochem Sc, Univ Pardubice, Czech Republic. - [email protected]

2-Dept Analytical Chem, Univ Pardubice, Czech Republic

References and Support

The study was supported by grant MZCR NT/14320.

  1. Bessems JGM, Vermeulen NPE (2001) Paracetamol (Acetaminophen)-induced toxicity: molecular and biochemical mechanisms, analogues and protective approaches. Crit Reviews Toxicology 31:55-138.
  2. Mazer M, Perrone J (2008) Acetaminophen-Induced nephrotoxicity: pathophysiology, clinical manifestations, and management. J Med Toxicology 4:2-6.
  3. James LP, Mayeux PR, Hinson JA (2003) Acetaminophen-induced hepatotoxicity. Drug Metabol Dispos 31:1499-1506.
Cookies help us deliver our services. By using our services, you agree to our use of cookies.