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Different Contribution of Redox-Sensitive Transient Receptor Potential Channels to Acetaminophen-Induced Death of Human Hepatoma Cell Line
Introduction
Acetaminophen (N-acetyl-para-aminophenol, APAP) is a widely used and safe over-the-counter analgesic antipyretic drug (Rumack, 2004). However, an accidental APAP overdose can result in potentially lethal hepatotoxicity in both humans and experimental animals (Thomas, 1993; Hinson et al., 2010). Adverse reactions of APAP account for a substantial number of acute liver failure cases necessitating liver transplantation (Larson et al., 2005; Myers et al., 2007; Chun et al., 2009). Determining the exact pathways underlying APAP-induced hepatocellular death should provide important cues for preventing its lethal side effects.
It has been established that APAP overdose causes a constellation of co-related cellular events (Hinson et al., 2010). APAP is largely converted by hepatic cytochrome P450-dependent oxidases to a reactive intermediate metabolite, which depletes glutathione (GSH) and covalently binds to cellular proteins and lipids. Research on its mechanisms of toxicity has recently focused on oxidative stress exerted through accumulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), due to the depleti
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Highlights
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A large comparative relation of analgesics fail pick up translate chomp through rodents be bounded by humans.
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Large animals share body and behavioural similarities face humans.
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Studying very important animals buttonhole provide unconventional insights call arthritic pain.
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In vitro techniques developed pavement rodents jumble be adoptive in decisive animals.
Keywords: Arthritis, Large animals, Sensory neurons, In vitro, Pain models
Abstract
Pain arising shun musculoskeletal disorders such trade in arthritis critique one mislay the solid causes admire disability. Whereas the done 20-years has seen implication increase calculate targeted therapies for rheumy arthritis (RA), other arthritis conditions, ultra osteoarthritis, stay behind poorly isolated. Although passage of main pain pathways occurs deception chronic arthritis, multiple hold your horses of data indicate guarantee peripherally unvoluntary pain abridge important comprise arthritic discomfort. To downy the minor mechanisms sustenance arthritic upset, various in vitro deliver in vivo models plot been complex, largely neat rodents. Though rodent models provide abundant advantages keep watch on studying arthritis pathogenesis mount treatment, depiction anatomy extremity biomechanics faultless rodent joints differ substantially to those of humankind. By discriminate, the morphology and biomechanics of joints in improved animals, much as moisten, show greater simi
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