Abstract
Background: Acetaminophen overdose is a leading cause of acute liver failure globally. Current treatment options, primarily N-acetylcysteine (NAC), have limitations. Mito- TEMPO (Mito-T), a mitochondria-targeted antioxidant, has shown potential in preclinical studies. This systematic review evaluated the evidence for Mito-T's hepatoprotective effects against acetaminophen-induced liver injury.
Methods: We conducted a comprehensive search of databases and grey literature following PRISMA guidelines. Studies published between 2000 and 2023 on Mito-T and acetaminopheninduced hepatotoxicity in animal models were included. Data on study characteristics, interventions, outcomes, and risk of bias were extracted.
Results: Six high-quality studies were included. Mito-T administration significantly reduced serum alanine transaminase (ALT) levels, a marker of liver injury, compared to controls. Mito- T also protects against hepatocellular necrosis, apoptosis, and mitochondrial dysfunction. These effects were likely mediated by Mito-T's ability to scavenge reactive oxygen and nitrogen species within mitochondria.
Conclusion: This review provides strong evidence that Mito-T effectively protects against acetaminophen- induced liver injury in animal models. Mito-T’s mechanisms of action address a critical pathophysiological pathway in acetaminophen toxicity. While limitations, including the use of animal models and potential for publication bias, exist, the findings suggest Mito-T holds promise as a novel therapeutic option. Further studies are needed to assess Mito-T's safety, pharmacokinetics, and optimal dosing in humans. Clinical trials comparing Mito-T against NAC are warranted if toxicity profiles are favorable. Additionally, investigating Mito-T's potential in other diseases involving oxidative stress is crucial.
Keywords: Acetaminophen, hepatotoxicity, mito-TEMPO, mitochondria, oxidative stress, antioxidants, systematic review.
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