Kaurenoic acid extracted from Sphagneticola trilobata reduces acetaminophen-induced hepatotoxicity through inhibition of oxidative stress and pro-inflammatory cytokine production in mice.
Leandro Marcondes-AlvesVictor FattoriSergio M BorghiYuri Lourenco-GonzalezAllan J C BussmannElisa Y HirookaRubia CasagrandeWaldiceu Aparecido VerriNilton S ArakawaPublished in: Natural product research (2017)
Acetaminophen (paracetamol) is a widely used analgesic and antipyretic drug that is safe at therapeutic doses. However, acetaminophen overdose can be fatal. Currently, the only treatment available is the N-acetyl cysteine. The diterpene kaurenoic acid (ent-kaur-16-en-19-oic acid, KA) is the major constituent of Sphagneticola trilobata (L.) Pruski. KA presents anti-inflammatory, anti-nociceptive and antioxidant properties. In this study, we evaluated the efficacy of KA in a model of acetaminophen-induced hepatotoxicity. KA increased, in a dose-dependent manner, the survival rate after acetaminophen overdose. KA reduced acetaminophen-induced hepatic necrosis and ALT and AST levels. KA decreased acetaminophen-induced neutrophil and macrophage recruitment, oxidative stress and the production of IL-33, TNF-α and IL-1β, alongside with normalisation of IL-10 levels in the liver. Therefore, KA showed preclinical efficacy in acetaminophen-induced hepatotoxicity and lethality.
Keyphrases
- drug induced
- liver injury
- diabetic rats
- oxidative stress
- high glucose
- anti inflammatory
- stem cells
- dna damage
- endothelial cells
- mesenchymal stem cells
- insulin resistance
- bone marrow
- adipose tissue
- ischemia reperfusion injury
- skeletal muscle
- spinal cord
- spinal cord injury
- single molecule
- high fat diet induced
- combination therapy