Unlabelled: Acetaminophen (APAP) overdose is a frequent cause of drug-induced liver injury and the most frequent cause of acute liver failure in the Western world. Previous studies with mouse models have revealed that impairment of mitochondrial respiration is an early event in the pathogenesis, but the exact mechanisms have remained unclear, and therapeutic approaches to specifically target mitochondria have been insufficiently explored. Here, we found that the reactive oxidative metabolite of APAP, N-acetyl-p-benzoquinoneimine (NAPQI), caused the selective inhibition of mitochondrial complex II activity by >90% in both mouse hepatic mitochondria and yeast-derived complexes reconstituted into nanoscale model membranes, as well as the decrease of succinate-driven adenosine triphosphate (ATP) biosynthesis rates. Based on these findings, we hypothesized that methylene blue (MB), a mitochondria-permeant redox-active compound that can act as an alternative electron carrier, protects against APAP-induced hepatocyte injury. We found that MB (<3 µM) readily accepted electrons from NAPQI-altered, succinate-energized complex II and transferred them to cytochrome c, restoring ATP biosynthesis rates. In cultured mouse hepatocytes, MB prevented the mitochondrial permeability transition and loss of intracellular ATP without interfering with APAP bioactivation. In male C57BL/6J mice treated with APAP (450 mg/kg, intraperitoneally [IP]), MB (10 mg/kg, IP, administered 90 minutes post-APAP) protected against hepatotoxicity, whereas mice treated with APAP alone developed massive centrilobular necrosis and increased serum alanine aminotransferase activity. APAP treatment inhibited complex II activity ex vivo, but did not alter the protein expression levels of subunits SdhA or SdhC after 4 hours.
Conclusion: MB can effectively protect mice against APAP-induced liver injury by bypassing the NAPQI-altered mitochondrial complex II, thus alleviating the cellular energy crisis. Because MB is a clinically used drug, its potential application after APAP overdose in patients should be further explored.
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Sci Rep
January 2025
Department of Food and Nutrition Sciences, College of Agricultural and Food Sciences, King Faisal University, Al Ahsa, 31982, Saudi Arabia.
The spent black tea extract was utilized in order to synthesize the spent black tea silver nanoparticles (SBT-AgNPs). Various parameters were tested to yield the best production of SBT-AgNPs. The characterization was conducted by X-Ray diffraction, Scanning electron microscopy, Zeta potential and energy dispersive X-ray (EDX).
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
PG & Research Department of Physics, AVVM Sri Pushpam College (Autonomous), [Affiliated to Bharathidasan University, Tiruchirappalli], Poondi, Thanjavur 613503, Tamil Nadu, India. Electronic address:
Development of bio-supported photocatalysts has become a pressing need in the field of environmental remediation. This work reports the synthesis of bio-enzyme (from banana peels) inherited (ZnO/g-CN) nanocomposite by simple soft chemical method and its photocatalytic degradation ability against the mixed dye (Methylene blue (MB) + Rhodamine-B (RhB)) under UV irradiation. Synthesized nanoparticles were characterized using experimental techniques XRD, FESEM, TEM, EDAX, XPS, UV-vis-NIR spectroscopy and FTIR.
View Article and Find Full Text PDFEnviron Monit Assess
January 2025
Department of Environmental Engineering, College of Engineering, University of Baghdad, Baghdad, Iraq.
RSC Adv
January 2025
College of Construction and Ecology, Shantou Polytechnic Shantou 515078 Guangdong China
This research focuses on the development of a novel Ru-doped TiO/grapefruit peel biochar/FeO (Ru-TiO/PC/FeO) composite catalyst, which exhibits exceptional photocatalytic efficacy under simulated solar light irradiation. The catalyst is highly effective in the degradation of rhodamine B (RhB), methylene blue (MB), methyl orange (MO), as well as actual industrial dye wastewater (IDW), and can be recovered magnetically for multiple reuse cycles. Significantly, the PCTRF-100 sample exhibited degradation efficiencies of 99.
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