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<https://discovery.ucl.ac.uk/id/eprint/10116697> <http://purl.org/dc/terms/title> "New aspects of the cellular effects of paracetamol and related antioxidants"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10116697> <http://purl.org/ontology/bibo/abstract> "In order to further understand the cellular effects of paracetamol and other related\r\nantioxidants, two different aspects have been studied;\r\n(i) Inhibition of DNA synthesis by paracetamol and related antioxidants.\r\nParacetamol is known to have antioxidant and radical scavenging properties and it\r\nhas been recently observed that paracetamol inhibits DNA synthesis through inhibition of\r\nribonucleotide reductase. This property is similar to that of hydroxyurea, a well known\r\nDNA synthesis inhibitor which also inhibits ribonucleotide reductase activity by destroying\r\nthe tyrosyl free radical. An objective of the present study is to determine whether\r\nparacetamol concentrations found in human therapeutic use or overdose are likely to inhibit\r\nDNA synthesis in humans. Other antioxidants were also included to broaden the scope of\r\nthe investigations since it seems likely that any antioxidant which has the right shape and\r\nsize to inhibit ribonucleotide reductase will inhibit DNA synthesis.\r\nTissues (testis, spleen and liver) from male Wistar rats were used in an ir? vitro tissue\r\nslice system to study the concentration-response relationships for inhibition of DNA\r\nsynthesis by different compounds. Inhibition of protein synthesis was used as a control to\r\nassess non-specific cell damage.\r\nParacetamol and hydroxyurea were found to inhibit DNA synthesis in a dosedependent\r\nmanner in vitro, with little effect on protein synthesis. Considerable variation\r\nin the sensitivity of the different tissues was also observed with an order of most\r\nsensitive to least sensitive tissue of spleen > testis > liver. Some other phenolic\r\nantioxidants have also been found to inhibit DNA synthesis specifically but this was not\r\na property shared by all phenolic antioxidants.\r\n(ii) Role o f apoptosis pathways in paracetamol-induced liver cell injury.\r\nPrevious studies have suggested that paracetamol can cause apoptotic changes. An\r\nobjective of the present study is to determine whether apoptotic pathways are involved in the hepatotoxic effects of paracetamol.\r\nA dose-response and a time course study were conducted with groups of male\r\nC57B1/6 mice and necrotic and apoptotic cell injury assessed. Necrotic cell injury was\r\nassessed at the microscopic level (H&E) and the degree of damage was correlated with\r\nplasma alanine aminotransferase (ALT) levels. Apoptotic changes were investigated\r\nusing the TUNEL method in liver sections, Western blot analysis for poly (ADP-ribose)\r\npolymerase (PAR?) cleavage in liver protein lysates and immunohistochemical staining\r\nfor Bax protein expression in liver sections. Essentially no evidence was found for the\r\ninvolvement of apoptotic pathways in liver cell injury due to paracetamol overdose."^^<http://www.w3.org/2001/XMLSchema#string> .
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