Hepatoprotective efficacy of the use of oxymethyl uracil in various experimental models

Introduction. The formation of toxic liver damage is carried out with the participation of various mechanisms of pathological processes. Chemicals, drugs and alcohol play a significant role. Timely and correct selection of correction drugs will help reduce the risk of toxic organ damage. The aim of the study is a comparative assessment of the hepatoprotective activity of oxymethyluracil in the early stages of exposure to various toxic agents. Materials and methods. The studies were carried out on male outbred white rats with a single injection of hepatotoxicants (carbon tetrachloride, paracetamol, ethanol) and a correction drug - oxymethyl uracil - followed by the study of biochemical parameters 1 and 3 days after the introduction of the chemical agent. Results. As a result of the studies carried out, it was found that specific metabolic changes are noted already one day after exposure to toxicants in the body of animals. Correction of tetrachloromethane and paracetamol intoxication with oxymethyl uracil leads to the normalization of the functional state of hepatocytes. Conclusion. Oxymethyl uracil exhibits hepatoprotective properties already in the early stages of acute toxic liver damage (1-3 days), being most effective in tetrachloromethane and paracetamol intoxication.

Аcute paracetamol intoxication

Paracetamol is non-narcotic analgesic and antipyretic of the central action from group of anilides, widely used in clinical practice. This drug has pronounced hepatotoxic effect which amplifies with alcohol. Paracetamol intoxication most frequently happens as a result of deliberate peroral intake of excessive doses of drug with a suicidal purpose. Undeliberate medicine poisoning is possible as a result of self-treatment.

Increased concentrations of procalcitonin in patients with paracetamol intoxication

Objectives Paracetamol intoxication is one of the causes of elevated procalcitonin concentrations unrelated to infection. We report a case series of two patients intoxicated with paracetamol whose laboratory data revealed a significant elevation of serum procalcitonin concentrations without clinical, radiological and/or biological evidence of infection. The underlying mechanism by which paracetamol triggers an increase in procalcitonin concentrations is still unclear. Case presentation We report two cases of paracetamol intoxication. Both patients were admitted to the Emergency Department (ED) and subsequently transferred to the Intensive Care Unit (ICU). The patients exhibited elevated procalcitonin levels during the first hours of admission without clinical and/or microbiological evidence of infection that could explain such increase. Notably, only Case 1 developed liver injury, with alterations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin and esterified bilirubin concentrations, which were not observed in Case 2. Conclusions The two patients showed elevated procalcitonin concentrations resulting from paracetamol intoxication, although only a patient exhibited signs of liver injury. These findings suggest that increased procalcitonin levels induced by a paracetamol overdose cannot be fully explained by hepatocyte injury alone, but other mechanisms involving other organs and tissues may also be associated. In any case, although this mechanism is not well understood, it is important to be aware of this limitation when using procalcitonin as a biomarker of infection in patients intoxicated with paracetamol.

Study of early metabolic changes in experimental animals with acute toxic exposure to paracetamol and against the background of correction

Paracetamol is one of the most widely used and popular over-the-counter analgesics and antipyretic drugs in the world. The number of registered cases of paracetamol-induced liver intoxication is constantly increasing in the world every year. It seems relevant to study early metabolic disorders in the liver in acute paracetamol intoxication and assess the effectiveness of the timely use of hepatoprotective drugs. The aim of this research is to study metabolic changes in laboratory animals at the early stages of exposure to paracetamol and against the background of correction with oxymethyluracil, ademetionine and mexidol. An experimental study of metabolic changes in laboratory animals under acute exposure to toxic doses of paracetamol and against the background of correction was carried out. Biochemical parameters in the blood serum of laboratory animals were investigated. The obtained results showed that the intake of paracetamol in toxic doses was accompanied by impaired hepatic metabolism at the earliest stages of exposure. With the corrective action of the studied drugs, metabolic disturbances caused by paracetamol intoxication were restored. At the same time, OMU, as well as ademetionine and ethylmethylhydroxypyridine succinate, is able to normalize metabolic changes after the acute toxic effect of paracetamol, and has a pronounced advantage in terms of the protein-synthetic function of hepatocytes.

Metabolic changes on the background of acute exposure to paracetamol and evaluation of the effectiveness of hepatoprotective drug

Introduction. In modern conditions, caused by the pandemic of a new type of viral infection Covid 19, the use of paracetamol, which has hepatotoxic properties in overdose, has increased. It seems relevant to study metabolic disorders in the liver in acute paracetamol intoxication and evaluate the effectiveness of the timely use of hepatoprotective drugs. The purpose of this study is an experimental assessment of metabolic changes at the early stages of paracetamol exposure and pharmacological correction of toxic liver lesions with oxymethyluracil in comparison with known hepatoprotectors - ademetionine and Mexidol. Material and methods. Acute intragastric administration of paracetamol to laboratory animals was performed, and the corrective effect of the drug oxymethyluracil was studied in comparison with “Heptor” and “Mexidol”. Biochemical studies of biomaterial of laboratory animals were conducted. Results. The analysis found the use of known hepatoprotectors and oxymethyluracil after exposure to paracetamol to normalize the biochemical parameters that characterize the functional state of the liver in laboratory animals. Conclusion. Oxymethyluracil, along with known hepatoprotectors, has a protective effect on the liver of laboratory animals under acute exposure to paracetamol comparable to, and in some cases exceeding, the corrective action of “Heptor” and “Mexidol”.

Presentations Related to Acute Paracetamol Intoxication in an Urban Emergency Department in Switzerland

Aim. To investigate the characteristics of Emergency Department (ED) presentations due to acute paracetamol intoxication. Methods. Retrospective observational study of patients presenting to the ED of Bern University Hospital between May 1, 2012, and October 31, 2018, due to a paracetamol overdose (defined as intake of >4 g/24 h). Cases were identified using the full-text search of the electronic patient database and were grouped into intentional (suicidal/parasuicidal) and unintentional intoxications (e.g., patient unaware of maximal daily dose). Results. During the study period, 181 cases were included and 143 (79%) of those were intentional. Compared to the patients in the unintentional group, patients in the intentional group were more often female (85% vs 45%, p<0.001) and younger (median age 23.0 vs 43.5 years, p<0.001), more frequently suffered from psychiatric comorbidities (93%, (including 49% with borderline personality disorder) vs 24%, p<0.001), and paracetamol was more often taken as a single dose (80% vs 13%, p<0.001). Although the median daily ingested dose was lower in the unintentional than in the intentional group (8.2 g vs 12.9 g, p<0.001), patients in the unintentional group presented later (29% vs 84% within 24 h of ingestion, p<0.001), included more cases of acute liver failure (nine (24%) vs six (4%), p<0.001), and were more often hospitalised (24% vs 52% treated as outpatients, p=0.002). There were no significant differences between the groups regarding drug-induced liver injury (seven cases (5%) in the intentional and one (3%) in the unintentional group) or fatalities (one in each group). Conclusions. The majority of presentations due to paracetamol poisoning were intentional, most commonly in female patients with borderline personality disorder. Patients with unintentional paracetamol intoxication had worse outcomes with respect to acute liver failure and hospitalisation. Future preventive measures should raise awareness of paracetamol toxicity in the general population and encourage particular attention and frequent follow-ups when prescribing paracetamol for vulnerable groups.