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Lophirones B and C halt acetaminophen hepatotoxicity by upregulating redox transcription factor Nrf-2 through Akt,

Najeeb O Aliyu1, Rafiat A Ajala-Lawal1, Taofeek O Ajiboye1

  • 1Antioxidants, Redox Biology and Toxicology Research Group, Department of Medical Biochemistry, College of Health Sciences, Nile University of Nigeria, Abuja, Nigeria.

Journal of Biochemical and Molecular Toxicology
|April 27, 2018
PubMed

Insights

Lophirones B and C protect against acetaminophen-induced liver injury by enhancing the Nrf-2 pathway. These compounds reduce liver damage and oxidative stress by modulating key signaling proteins like Akt, PI3K, and PKC.

Area of Science:

  • Pharmacology
  • Hepatology
  • Natural Products Chemistry

Background:

  • Acetaminophen overdose is a leading cause of acute liver failure.
  • Natural compounds are explored for their therapeutic potential in drug-induced liver injury.
  • Lophirones B and C are plant-derived compounds with potential protective effects.

Purpose of the Study:

  • To elucidate the protective mechanism of lophirones B and C against acetaminophen-induced hepatotoxicity.
  • To investigate the role of key signaling pathways, including NF-κB, Akt, Nrf-2, PI3K, and PKC, in this protective effect.

Main Methods:

  • Mice were pretreated with lophirones B and C for 7 days.
  • Acetaminophen challenge was administered on day 7.
  • Liver tissues and serum biomarkers were analyzed for molecular and biochemical changes.
  • Levels of NF-κB, Akt, Nrf-2, PI3K, and PKC were quantified.

Main Results:

  • Acetaminophen increased NF-κB and decreased Akt in mouse liver.
  • Lophirones B and C reversed the acetaminophen-induced increase in NF-κB and increased Akt levels.
  • Lophirones B and C enhanced Nrf-2, PI3K, and PKC levels.
  • These compounds prevented alterations in serum biomarkers of hepatic injury and reduced oxidative stress.

Conclusions:

  • Lophirones B and C exhibit significant hepatoprotective effects against acetaminophen toxicity.
  • The mechanism involves the enhancement of the Nrf-2 pathway via Akt, PI3K, and PKC signaling.
  • These findings suggest potential therapeutic applications for lophirones B and C in managing liver injury.
Keywords:
Lophira alatachalcone dimersoxidative stressredox transcription factorupstream kinases

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