Effects of caffeine on brain antioxidant status and mitochondrial respiration in acetaminophen-intoxicated mice

Autor: Guilherme Pires Amaral, Thaís Posser, Cristiane Lenz Dalla Corte, Sílvio Terra Stefanello, Cintia C. Tassi, Débora Farina Gonçalves, Félix Alexandre Antunes Soares, Nelson Rodrigues de Carvalho, Jeferson Luis Franco
Rok vydání: 2020
Předmět:
Zdroj: Toxicol Res (Camb)
ISSN: 2045-452X
Popis: Hepatic encephalopathy is a pathophysiological complication of acute liver failure, which may be triggered by hepatotoxic drugs such as acetaminophen (APAP). Although APAP is safe in therapeutic concentration, APAP overdose may induce neurotoxicity, which is mainly associated with oxidative stress. Caffeine is a compound widely found in numerous natural beverages. However, the neuroprotective effect of caffeine remains unclear during APAP intoxication. The present study aimed to investigate the possible modulatory effects of caffeine on brain after APAP intoxication. Mice received intraperitoneal injections of APAP (250 mg/kg) and/or caffeine (20 mg/kg) and, 4 h after APAP administration, samples of brain and blood were collected for the biochemical analysis. APAP enhanced the transaminase activity levels in plasma, increased oxidative stress biomarkers (lipid peroxidation and reactive oxygen species), promoted an imbalance in endogenous antioxidant system in brain homogenate and increased the mortality. In contrast, APAP did not induce dysfunction of the mitochondrial bioenergetics. Co-treatment with caffeine modulated the biomarkers of oxidative stress as well as antioxidant system in brain. Besides, survival assays demonstrated that caffeine protective effects could be dose- and time-dependent. In addition, caffeine promoted an increase of mitochondrial bioenergetics response in brain by the enhancement of the oxidative phosphorylation, which could promote a better energy supply necessary for brain recovery. In conclusion, caffeine prevented APAP-induced biochemical alterations in brain and reduced lethality in APAP-intoxicated mice, these effects may relate to the preservation of the cellular antioxidant status, and these therapeutic properties could be useful in the treatment of hepatic encephalopathy induced by APAP intoxication.
Databáze: OpenAIRE