Paracetamol Ingestion Research Articles

Bugs on Drugs: Paracetamol Exposure Reveals Genotype-Specific Generational Effects on Life History Traits in Drosophila melanogaster.

Few investigations have been made to determine whether pharmaceutical drugs cause any generational effects. These effects can be divided into intergenerational and transgenerational effects. In insects, the F1 offspring of exposed individuals are considered to show intergenerational effects (as they have been exposed as germ cells or early embryos), while the F2 generation is fully non-exposed and considered to show transgenerational effects. Here, the common over-the-counter (OTC) drug, paracetamol, is investigated for genotype-specific responses and effects across generations on three life-history traits: fecundity, longevity, and spontaneous locomotor activity levels in the model species Drosophila melanogaster. Seven isofemale D. melanogaster lines were exposed to a high and intermediate dose of paracetamol determined by a dose-response curve. NMR investigations verified the long-term presence of paracetamol in the food substrate. Phenotypic effects of paracetamol ingestion were investigated on flies exposed to the drug and in their offspring and grand-offspring. The dose-response curve indicated genotype-specific responses to paracetamol. In the following experiment, all traits investigated displayed significant effects of paracetamol ingestion for at least one of the seven isofemale lines, and we detected strong genotype-specific responses to paracetamol. Fecundity tended to increase in individuals directly exposed to the drug whereas fecundity in the F2 generation was reduced (transgenerational). Longevity generally decreased in directly exposed individuals but tended to increase in F1 offspring (intergenerational). Paracetamol effects on spontaneous locomotor activity were primarily detected as transgenerational effects and were rarely seen in directly exposed individuals. However, across lines, no clear overall trend could be determined for any trait. The generational effects and marked genotype-specific response to paracetamol warrants further investigation of both genotype-specific responses and generational effects in general.

Maternal prenatal paracetamol ingestion and scholastic attainments of the offspring.

Background: Fetal exposure to paracetamol (acetaminophen) has been shown to be associated with asthma and other atopic disorders, as well as behavioural problems including hyperactivity, in childhood. However, there is little information on scholastic abilities among children exposed to paracetamol in pregnancy. Objectives: To determine whether there are any differences in scholastic abilities among the offspring of women who ingested paracetamol during pregnancy compared with non-exposed children. Methods: Mothers enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) had recorded the frequency with which they had taken the medication over two time periods during pregnancy: i) the first 18weeks and ii) 18-32weeks. The offspring have been followed up ever since. For this study we use as outcomes: a) 14 tests of ability at reading and 2 of spelling using the study's tests and the national education system test results; b) 6 of mathematical abilities including tests of arithmetic and mathematical reasoning, and c) 1 of scientific understanding. Multiple regression was used, adjusting for 15 different exposures including reasons for taking the medication as well as demographic features. Results: Almost all unadjusted and adjusted mean differences were negative (i.e., those exposed to maternal intake of paracetamol did less well), but negative associations for exposures between 18 and 32weeks of gestation were much more evident than for exposures earlier in pregnancy. Of the later exposures, after adjustment, 12 of the 23 scholastic tests were associated with prenatal exposure to paracetamol at p < 0.05. These negative effects were found in the girls (12 tests at p < 0.05) but not boys (0 tests at p < 0.05). Conclusion: Evidence from this longitudinal study suggests that maternal exposure to paracetamol is associated with disadvantages to the offspring in scholastic abilities such as mathematics and reading at secondary school ages. This raises the question as to whether there are longer-lasting effects on educational attainment from age 15years onwards, including at university level. Clearly these results should be tested in other settings, but meanwhile they add to a growing accumulation of known adverse effects of exposure to paracetamol in pregnancy.

Patterns and outcomes of paracetamol poisoning management in Hamad Medical Corporation, Qatar: A retrospective cohort study.

We aimed to investigate the characteristics and clinical outcomes of paracetamol poisoning and paracetamol overdose in Qatar. This retrospective cohort study included patients admitted to the emergency department (ED). We included patients who presented with excessive paracetamol ingestion, between December 2018 and September 2019. The primary outcomes were describing the characteristics and outcomes of paracetamol overdose (from a suicidal overdose or accidental overdose, dose ≤ 150 mg/kg, when serum levels of <60 mmol/L) or dose ingested (≤75 mg/kg) with staggered ingestion poisoning due to suicidal attempt or accidental attempt, defined as the dose ingested (>150 mg/kg), acute ingestion, nomogram level more than the treatment line, or dose ingested (>75 mg/kg) with staggered ingestion, and assessing the management of excessive paracetamol ingestion. Secondary outcomes included evaluation of the time difference between ingestion and time of administration, hospitalization, and adverse drug events. Significant differences were detected between patients who presented with paracetamol overdose and those who presented with paracetamol toxicity. A total of 69 patients were analyzed, of whom 43 received paracetamol overdose (mean age 27.5 ± 11.1 years) and 26 had paracetamol poisoning (mean age 25 ± 6.22 years). Paracetamol poisoning was identified in 26% of the patients with a 24.3% history of psychiatric illness, compared to 18.6% with paracetamol overdose. More patients presented with paracetamol toxicity in the time between ingestion and obtaining serum levels compared to the overdose group. A significantly longer length of hospitalization was observed in the toxicity group. A significantly higher number of patients in the toxicity group received N-acetylcysteine (NAC). More hypotension and rashes were observed among those who received NAC in the toxicity group. Patients presenting to the ED due to paracetamol toxicity are not uncommon, and most cases occur in young adults, and few in patients with a history of psychiatric illness, suggesting that preventive approaches are highly required.

OUTCOME OF PARACETAMOL(ACETAMINOPHEN) POISONING CASES AT TERTIARY CARE HOSPITAL-A RECORD BASED RETROSPECTIVE STUDY

Paracetamol (PCM, Acetaminophen) is one of the most widely used drug in the world. It is an effective mild analgesic, antipyretic agent which is inexpensive and mostly sold as an over the counter drug. Paracetamol or acetaminophen overdose is a common means of self poisoning worldwide due to its wide availability and accessibility. A record based retrospective study was conducted at a tertiary care hospital to determine the demographic prole of paracetamol poisoning cases and to record the outcome of paracetamol poisoning cases .Primary outcome in terms of development of hepatotoxity and days of hospitalization and Secondary outcome in terms of recovery status as either survived or expired. Datas of 70 patients admitted with history of paracetamol poisoning in the past year was obtained and analysed for demodraphic and clinical features.It was observed that most predominance of paracetamol overdose in young age with median age of 26 with female preponderance and Hepatotoxicity was seen in only six cases of all paracetamol overdose with no mortalities.This study concluded that Paracetamol poisoning is frequently seen in young females attempting suicide. In India the rate of hepatic toxicity tends to be low. Mortality and Morbidity were not seen despite high doses of paracetamol ingestion.

HEPATOTOXICITY EFFECTS OF PARACETAMOL-DENIK CLEANSER® CO-ADMINISTRATION

Aim and Objective: The concurrent use of herbal products with orthodox medicine is on the rise with the risk of herb-drug interaction that could be beneficial or harmful to the body. Paracetamol (acetaminophen) is an anti-pyretic and analgesic drug metabolized by CYP2E1 to give the major hepatotoxin, N-acetyl-p-benzoquinone imine (NAPQI). Denik cleanserâ is an oral herbal preparation from plants part of Occimum grattissimum, Colocynthis citrullus, Khaya ivorensi. The aim of this study was to evaluate the hepatotoxic effects triggered by Denikâ and paracetamol co-administration in rats. The study sought to mimic conventional usage of Denik cleanserâ followed by ingestion of paracetamol, a likely scenario given the popularity of both compounds. Method: Twenty animals were randomly assigned to four groups, the first group (control) received 0.3 mL distilled water, 2nd group received paracetamol 100 mg/kg, 3rd group received Denik cleanserâ2 mL/kg while the 4th group received both paracetamol and Denik cleanserâ at 100 mg/kg and 2 mL/kg daily for 3 days after which biochemical and histological analysis were carried out. Results: From histological analysis revealed that rats that received Denikâ-only and Denikâ/paracetamol (concomitantly) showed markedly distorted liver architecture compared to control indicating toxicity. Similarly, the biochemical analysis results showed a significant (p&lt;0.05) increase in AST and ALT for the Denikâ/paracetamol group compared to the control group indicating a hepatotoxic event. A non-significant increase in ALP and GGT were also observed in the Denik cleanserâ + paracetamol group. Enhanced metabolism of paracetamol by Denik cleanserâ to NAPQI (hepatotoxic metabolite) is indicated as possible mechanism. Conclusion: The results of this study demonstrated the in vivo potential for a herb/drug interaction involving paracetamol and Denik cleanserâ resulting in liver injury.Therefore, caution is strongly advised against its casual, non-medically supervised usage. Peer Review History: Received: 3 November 2022; Revised: 7 December; Accepted: 9 January 2023, Available online: 15 January 2023 Academic Editor: Dr. Nuray Arı, Ankara University, Turkiye, ari@ankara.edu.tr Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Dr. Sangeetha Arullappan, Universiti Tunku Abdul Rahman, Malaysia, sangeetha@utar.edu.my Prof. Hüsniye Kayalar, Ege University, Turkey, husniyekayalar@gmail.com Similar Articles: CO-ADMINISTRATION OF GOKO HERBAL CLEANSER AND PARACETAMOL: A HERB-DRUG INTERACTION STUDY IN-VITRO ANTIOXIDANT, LIPID PEROXIDATION INHIBITION AND LIPID PROFILE MODULATORY ACTIVITIES OF HB CLEANSER®BITTERS IN WISTAR RATS

Assessing Paracetamol Overdose in Children: Acceptability and Potential Market for a Non-Invasive Testing Device.

Assessment of paracetamol overdose in children and teenagers in the emergency department (ED) requires blood, taken 4 hours post ingestion. A commercial partner developed transdermal paracetamol measuring technology. This work aims to understand the acceptability of such a device, and potential market size. A questionnaire study was undertaken with children and parents attending Alder Hey Children's Hospital, and healthcare professionals (HCP) involved in their care. A retrospective audit of paracetamol ingestion presenting to a paediatric ED was undertaken. One hundred forty-three questionnaires were distributed, and 139 returned (response rate 97.2%), comprising 55 children, 52 parents and 32 HCP (recruited between August-October 2019). Overall device acceptability, assessed by favourability of appearance and willingness to wear was high, at 60.0% and 81.5% respectively. Concerns raised included bulky size and weight, and concern regarding the duration younger children would tolerate wearing the device. All groups, including children, ranked accuracy of results as the most important device feature and device comfort the least important. Parents prioritised avoidance of blood tests more than children. One hundred twenty-seven children presented to ED with paracetamol ingestion (September 2017-August 2018), with 57 (44.9%) categorised as accidental overdose. Overall, 106 (83.4%) required paracetamol concentration measuring, and 25 (19.7%) of these required treatment with N-acetylcysteine. Extrapolating nationally, over 7000 children will present with accidental overdose per annum in the UK. Acceptability of a non-invasive paracetamol sensor was high in all groups, provided accuracy could be assured.

Molecular mechanism of the protective effect of adenosine triphosphate against paracetamol-induced liver toxicity in rats.

Toxic doses of paracetamol are also known to be close to therapeutic doses. This study aimed to biochemically investigate the protective effect of ATP against paracetamol-induced oxidative liver injury in rats and to examine the tissues histopathologically. We divided the animals into the paracetamol alone (PCT), ATP + paracetamol (PATP), and healthy control (HG) groups. Liver tissues were examined biochemically and histopathologically. Malondialdehyde level, AST and ALT activity in the PCT group were significantly higher than those in the HG and PATP groups (p < 0.001). The glutathione (tGSH) level, superoxide dismutase (SOD) and catalase (CAT) activity in the PCT group was significantly lower than that in the HG and PATP groups (p < 0.001), while animal SOD activity was significantly different between the PATP and HG groups (p < 0.001). The activity of CAT was almost the same. In the group treated with paracetamol alone, lipid deposition, necrosis, fibrosis, and grade 3 hydropic degeneration were observed. No histopathological damage was observed of the ATP-treated group, except for grade 2 edema. We discovered that ATP reduces the oxidative stress caused by paracetamol ingestion and protects against paracetamol-induced liver injury at the macroscopic and histological levels.

Silk Fabric Decorated with Thermo-Sensitive Hydrogel for Sustained Release of Paracetamol.

Paracetamol is a safe and widely used antipyretic and analgesic drug, however, with the drawbacks of gastrointestinal first-pass effect and short intervals of administration. Transdermal drug delivery system can effectively avoid the liver metabolism caused by excess oral ingestion of paracetamol. Herein, a silk fabric-based medical dressing decorated by a thermo-responsive hydrogel for sustained release of paracetamol is proposed. Genipin as a bio-safe cross-linker is applied to assist gelation of a thermo-responsive hydrogel system coupled with chitosan and glycerol-phosphate disodium salt around body temperature (37°C), as well as densifying the microporous gel to improve mechanical strength. The in situ sol-gel transition enabled hydrogel well penetrate and coat the silk fabric, forming a hierarchical hydrogel structure capable of prolonging the sustained release of drug to 12h, twice as long as a blank fabric. The silk fabric with a thin gel coating maintains a good water vapor transmission rate, compatible for skin contact application. The drug release properties can be tuned by regulating the genipin content and fabric braiding structure. The silk fabric dressing exhibits temperature-dependent instant release behavior within the first 2h. The sustained release mechanism of paracetamol well matches with the Korsmeyer-Peppas model in a non-Fickian diffusion.

Securing a diagnosis in patients presenting with suspected paracetamol (acetaminophen) poisoning: Aretrospective cohort study.

Paracetamol (acetaminophen) is the most commonly ingested drug in self-poisoning. The correlation between an ingested self-reported dose of paracetamol and plasma paracetamol concentration is moderate. The usefulness of this correlation to rule out paracetamol ingestion has to be investigated. The objective of this study is to evaluate the performance of medical history in diagnosis of paracetamol ingestion in patients admitted to the Emergency Department (ED) for deliberate self-poisoning. This retrospective cohort study was carried out in two EDs at an urban university hospital in Toulouse, France, from January 1 to June 30, 2018. All patients older than 15 years of age attending the ED for suspected deliberate self-poisonings who underwent blood testing were included. Medical history was considered positive for paracetamol intoxication if patients directly reported the use of paracetamol for deliberate self-poisoning during their ED admission or if paramedics reported the presence of paracetamol packages at the patient's home. We defined paracetamol ingestion as any concentration of paracetamol > 5 mg/L measured on presentation. We included 709 patients. 151 (21%) patients had a positive plasma paracetamol concentration. 165 (23%) patients revealed a positive medical history in terms of paracetamol ingestion. 29 (4%) patients had a false-negative medical history, and 45 (6%) patients had a false-positive history. The sensitivity of the medical history (95% confidence interval) was 79% (72-87), and its specificity was 92% (89-94). Diagnosis of self-poisoning involving paracetamol cannot be made using patient's medical history alone. Screening for paracetamol intoxication is proposed.

What is the Effect of Paracetamol (Acetaminophen) Ingestion on Exercise Performance? Current Findings and Future Research Directions.

In recent years, studies have explored the effects of paracetamol (acetaminophen) ingestion on exercise performance. However, due to the contrasting findings, there is still no consensus on this topic. This article provides an overview of the effects of paracetamol on endurance, sprinting, and resistance exercise performance. Studies have reported that paracetamol ingestion may be ergogenic for endurance performance. These effects occur when paracetamol is ingested 45-60min before exercise and appear to be more pronounced in time-to-exhaustion versus time-trial tests. Besides endurance, paracetamol ingestion 30min before exercise increases mean power during repeated cycling sprints in interval training involving repeated 30-s all-out bouts. Preliminary data on paracetamol ingestion also suggest: (a) improved endurance performance in the heat; (b) an improvement in single sprint performance, at least when paracetamol is ingested following exercise-induced fatigue; and (c) attenuation of the decline in muscular strength that occurs with repeated maximum contractions. An ergogenic effect of paracetamol is most commonly observed when a dose of 1500mg is ingested 30-60min before exercise. Despite these performance-enhancing effects, the aim of this article is not to promote paracetamol use, as side effects associated with its consumption and ethical aspects need to be considered before utilizing paracetamol as an ergogenic aid. Future research on this topic is still needed, particularly related to paracetamol dosing, timing of ingestion, and the effects of paracetamol in females and elite athletes.

Has the time come to stop routine N-acetylcysteine treatment in young children in Denmark? A review of 300 suspected paracetamol overdoses in children aged 0-6 years.

To evaluate the prevalence of potentially hepatoxic paracetamol ingestion and associated N-acetylcysteine treatment in young children suspected of paracetamol poisoning. A retrospective cohort study of children aged 0-6years suspected of paracetamol poisoning with a related plasma-paracetamol measurement in the Capital Region of Denmark in the period 2010-2017. Data from the clinical laboratory system were linked to data from electronic patient records via the unique identification number given to all Danish residents. Of 297 children included, suspected single paracetamol overdoses were present in 281 (95%). Sixty-nine per cent were treated with N-acetylcysteine, and the mean treatment period was 20.3h (SD 20.8). A maximum of 6 (2%) of the children suspected of single overdose had plasma-paracetamol concentrations that exceeded the recommended treatment thresholds. No cases of severe hepatotoxicity were registered. Adverse events to N-acetylcysteine-treatment were registered in 3 (2%) children including one anaphylactoid reaction (0.5%). This study shows that initiating N-acetylcysteine as a 'one size fit all' treatment regimen in all children aged 0-6years with a suspected single paracetamol overdose leads to substantial overtreatment. The data support that it is feasible to initiate N-acetylcysteine within 10h based on an early plasma-paracetamol test.

Comparing development of liver injury using the two versus three bag acetylcysteine regimen despite early treatment in paracetamol overdose

Introduction Some studies have reported that early administration of acetylcysteine using a 3-bag regimen may not fully prevent development of liver injury in some patients. We compared the incidence of acute liver injury (ALI) in patients receiving acetylcysteine within eight hours of ingestion between the two-bag acetylcysteine regimen (200 mg/kg over four hours, 100 mg/kg over 16 h) and the three-bag regimen (150 mg/kg over 1 h, 50 mg/kg over 4 h, 100 mg/kg over 16 h). Method This was a retrospective cohort study of the two-bag and three-bag acetylcysteine regimens from Monash Health, Victoria, Australia (2009–2020), compared to the three-bag acetylcysteine regimen data from the Canadian Acetaminophen Overdose Study (CAOS) database (1980–2005). The inclusion criteria included patients with an acute single ingestion of paracetamol; normal aminotransferases on presentation and acetylcysteine administered within eight hours post-overdose. The primary outcome was development of ALI (defined as: peak aminotransferase >150 IU/L). Results At Monash Health, 191 patients were treated with the two-bag acetylcysteine regimen, and 180 patients with the three-bag regimen. The CAOS cohort provided 515 patients treated with the three-bag regimen. ALI developed in 1.6% (3/191) of the two-bag Monash Health group, 2.2% (4/180) of the three-bag Monash Health group (difference −0.6%, p 0.7), and 2.9% (15/515) of the three-bag CAOS group (difference compared to two-bag −1.3%, p 0.4). Hepatotoxicity (ALT >1000) developed in 0.5% (1/191) of patients treated with the two-bag regimen, 1.7% (3/180) in the Monash Health three-bag regimen and 1% (5/515) of the three-bag CAOS group. There were no statistically significant differences between groups. Conclusions ALI and hepatotoxicity were observed in a small, comparable percentage of patients despite early acetylcysteine administration using the two-bag and three-bag regimens. Repeating blood tests at the end of acetylcysteine treatment will identify these patients and indicate those requiring continuation of acetylcysteine.

Effects of Paracetamol (Acetaminophen) Ingestion on Endurance Performance: A Systematic Review and Meta-Analysis.

Several studies explored the effects of paracetamol (acetaminophen) ingestion on endurance performance, but their findings are conflicting. Therefore, this review aimed to conduct a meta-analysis examining the effects of paracetamol ingestion on endurance performance. Five databases were searched to find relevant studies. The PEDro checklist was used to assess the methodological quality of the included studies. Data reported in the included studies were pooled in a random-effects meta-analysis. A total of ten studies with good or excellent methodological quality were included in the meta-analysis (pooled n = 141). All included studies had a randomized, double-blind, crossover design. In the main meta-analysis, there was no significant difference between the effects of placebo and paracetamol on endurance performance (Cohen’s d = 0.09; 95% confidence interval (CI): −0.04, 0.22; p = 0.172). However, an ergogenic effect was found when we considered only the studies that provided paracetamol 45 to 60 min before exercise (Cohen’s d = 0.14; 95% CI: 0.07, 0.21; p < 0.001). In a subgroup analysis that focused on time-to-exhaustion tests, there was a significant ergogenic effect of paracetamol ingestion (Cohen’s d = 0.19; 95% CI: 0.06, 0.33; p = 0.006). There was no significant difference between placebo and paracetamol in a subgroup analysis that focused on time trial tests (Cohen’s d = 0.05; 95% CI: −0.12, 0.21; p = 0.561). In conclusion, paracetamol ingestion appears to enhance performance (a) in time-to-exhaustion endurance tests and (b) when consumed 45 to 60 min before exercise.

Pretreatment with Salvadora persica L. (Miswak) aqueous extract alleviates paracetamol-induced hepatotoxicity, nephrotoxicity, and hematological toxicity in male mice.

Background and Aim:Paracetamol (PCM) ingestion is one of the most frequent global causes of toxicity. Salvadora persica L. is a plant that among many other effects exhibits potent antioxidant, anti-inflammatory, antimicrobial, and anticancer effects. In this study, we investigated the possible protective effect of S. persica aqueous extract in the PCM overdose-induced liver and kidney injury and hematological changes in a mice model.Materials and Methods:Mice were given PCM with and without S. persica pretreatment. Blood cell counts and liver and kidney function biomarkers were measured. Liver and kidney samples were histologically examined.Results:A single overdose of PCM caused significant elevations of alanine and aspartate transaminases, alkaline phosphate, bilirubin, urea, uric acid, and creatinine compared with the control group. In addition, PCM toxicity significantly lowered red blood cell count but insignificantly increased both white blood cell and platelet counts in comparison to the control mice. Pretreatment with S. persica significantly prevented PCM-induced changes in hepatic and renal biomarkers. S. persica also caused marked reversal of hematological changes. Histologically, the liver and kidney showed inflammation and necrosis after PCM treatment, which were significantly reduced in mice pretreated with S. persica.Conclusion:Taken together, S. persica significantly inhibited PCM-induced renal, hepatic, and hematological toxicity, pointing to its possible use in the treatment of liver and renal disorders.

Nephroprotective property of Trifolium repens leaf extract against paracetamol-induced kidney damage in mice.

Paracetamol-induced toxicity is one of the major drawbacks in the treatment of inflammatory conditions. The present study was performed to find out the impacts of phenolic compounds in the Trifolium repens (white clover) leaves (TR) against the paracetamol-induced nephrotoxicity in mice. The extract was administered orally to mice in different doses (1, 2, and 3mL having a dry mass of 11.0mg/mL) along with paracetamol (300mg/kg) alone or in combination. Kidney histology, serum renal function tests, serum electrolytes, reduced glutathione, and lipid peroxidation were evaluated. Paracetamol significantly affected kidney weight, renal profile biochemistry, serum electrolytes, reduced glutathione, and thiobarbituric acid reactive substances (as lipid peroxidation) in mice. The amount of total phenolic compounds identified in the extract was 8.89mg/g, representing 80.8% of the extract. The simultaneous administration of the TR extract leads to the normalization of all those parameters, which were deviated due to paracetamol ingestion. Kidney histological examination showed that nephrotoxicity was induced due to paracetamol, while the extract rich in phenolic compounds acts as therapeutic agents. The administration of extract also normalized the reduced glutathione from 0.837 to 2.21 of the paracetamol and paracetamol with 3-mL extract, respectively. Lipid peroxidation in the kidney was significantly (p < 0.05) declined by the extract (0.435µmol/g) as compared to PC (3.96µmol/g). In conclusion, TR extract possesses active beneficial phenolic compounds with nephroprotective function.

Hepatoprotective effect of Omega-3 PUFAs against acute paracetamol-induced hepatic injury confirmed by FTIR.

Acute paracetamol over dose-induced hepatotoxicity is considered an important medical hazard especially among women. Omega-3 long-chain polyunsaturated fatty acids (Omega-3 PUFAs) daily doses are nowadays recommended for their antioxidant and anti-inflammatory potentials. Fourier transform infrared (FTIR) spectroscopy is considered a reliable method in analyzing cellular alterations and is now efficiently used to diagnose several diseases and the efficacy of drugs even in the early stages. The aim of our study was to evaluate the hepatoprotective effect of Omega-3 PUFAs against paracetamol-induced hepatotoxicity in rats confirmed through measuring protein alterations in hepatocytes by FTIR. Rats were pretreated with Omega-3 PUFAs (50 and 100 mg/kg) for 21 days prior to oral ingestion of paracetamol. FTIR results revealed that Omega-3 PUFAs (50 mg/kg) limited the toxic effects of paracetamol by restoring the hepatic amide I to amide II ratio. In addition; biochemical analyses demonstrated that serum ALT, AST, Cholesterol, LDL-cholesterol and Il-6 levels as well as hepatic TNF-α, MDA, NOx levels were decreased. Besides; serum HDL-cholesterol level and hepatic GSH level were increased. Histopathological examinations of hepatic sections validated the hepatoprotective potential. The overall effect of this dose was comparable to those of the usual recommended hepatoprotective supplement; silymarin. In conclusion; it would be recommended to use Omega-3 PUFAs in low doses on daily bases as a hepatoprotective agent.

Hepatotoxicity in a child following an accidental overdose of liquid paracetamol

Introduction: Accidental pediatric liquid paracetamol exposure is common. Most children do not require treatment with acetylcysteine and acute liver injury is rare.Case report: An otherwise well 3-year-old (15.4 kg) girl with recent vomiting and low-grade fever presented 1 h post-accidental ingestion of up to 150 mL of 24 mg/mL (240 mg/kg) of liquid paracetamol. Paracetamol concentrations 2 and 4 h post-ingestion were 105 and 97 mg/L, respectively, both below the nomogram treatment threshold so acetylcysteine was not administered. The ALT was elevated to 52 U/L 4 h post-ingestion, and then 219 U/L at 17 h, so intravenous acetylcysteine was commenced at 25 h. ALT peaked at 1393 U/L 5d post-ingestion, and INR peaked at 1.5 at 44 h post-ingestion. Acetylcysteine continued for 64 h and she made an uneventful recovery. Paracetamol metabolites were measured including, nontoxic glucuronide and sulphate conjugates and toxic cytochrome P450 (CYP) metabolites (cysteine and mercapturate). The apparent paracetamol half-life was 6.3 h. Her CYP metabolites were higher than usual, 11% of total metabolites. Glucuronide and sulphate conjugates accounted for 71 and 18% of total metabolites, respectively.Conclusion: This uncommon case of hepatotoxicity in a child following accidental liquid paracetamol ingestion may have been due to increased susceptibility from a recent viral illness with decreased oral intake, as evidenced by the higher proportion of CYP metabolites.

Resveratrol Pretreatment Ameliorates p53-Bax Axis and Augments the Survival Biomarker B-Cell Lymphoma 2 Modulated by Paracetamol Overdose in a Rat Model of Acute Liver Injury

Background: The potential protective effects of resveratrol (RES) on the modulation of hepatic biomarkers of apoptosis and survival, p53-Bax axis, and B-cell lymphoma 2 (Bcl-2) in an animal model of paracetamol-induced acute liver injury have not been investigated before. Methods: The model group of rats received a single dose of paracetamol (2 g/kg, orally), whereas the protective group of rats were pretreated for 7 days with RES (30 mg/kg, i.p.) before they were given a single dose of paracetamol. All rats were then sacrificed 24-h post paracetamol ingestion. Results: Histology images showed that paracetamol overdose induced acute liver injury, which was substantially protected by RES. Paracetamol significantly (p < 0.05) modulated p53, apoptosis regulator Bax, Bcl-2, tumor necrosis factor-alpha, interleukin-6, inducible nitric oxide synthase, malondialdehyde, superoxide dismutase, glutathione peroxidase, alanine aminotransferase, and aspartate aminotransferase, which were significantly protected by RES. We further demonstrated a significant (p< 0.01) correlation between either p53 or Bcl-2 scoring and the levels of inflammatory, nitrosative stress, and liver injury biomarkers. Conclusion: We demonstrate a substantial protection by RES pretreatment against paracetamol-induced modulation of p53-Bax axis, Bcl-2, and other acute liver injury biomarkers in rats.

Vitamin C, omega-3 and paracetamol pharmacokinetic interactions using saliva specimens as determiners.

Background With its low side effects profile and availability as an over-the-counter drug, paracetamol has been utilized extensively worldwide as an antipyretic and analgesic agent for decades. This is associated with the increasing concern over its ease of access and/or unawareness of the consumers to this issue of paracetamol-induced hepatotoxicity. Paracetamol-induced liver injury today is a big problem where most of the researchers are interested in the possible role of the naturally available antioxidants to ameliorate hepatotoxicity through kinetic interference. So the present study was designed to evaluate the effect of vitamin C and omega-3 on the pharmacokinetic property of paracetamol. Methods Six young (average age 29) healthy volunteers participated in the study. The study included three consecutive periods, each of which preceded by overnight fasting and separated by 6 day washout periods. The first period involved the ingestion of a single paracetamol dose. The second one included the ingestion of paracetamol and vitamin C concomitantly, and the final period included paracetamol plus omega-3. Saliva samples were collected and prepared for High-performance liquid chromatography analysis. Results There was a significant increase in saliva paracetamol level after 30 min of administration when given concomitantly with vitamin C compared with the remaining groups. No significant differences in the paracetamol concentration profile between the subjects for each group were observed at 60, 90, 120 and 150 min in all treated groups. Conclusion Concurrent administration of vitamin C with paracetamol increases significantly the Cmax level (maximum measured concentration) in saliva and increases the extent of absorption and the possibility of drug-drug interaction and risk of side effects.

Paracetamol poisoning-related hospital admissions and deaths in Australia, 2004-2017.

To assess the numbers of paracetamol overdose-related hospital admissions and deaths in Australia since 2007-08, and the overdose size of intentional paracetamol overdoses since 2004. Retrospective analysis of data on paracetamol-related exposures, hospital admissions, and deaths from the Australian Institute of Health and Welfare National Hospital Morbidity Database (NHMD; 2007-08 to 2016-17), the New South Wales Poisons Information Centre (NSWPIC; 2004-2017), and the National Coronial Information System (NCIS; 2007-08 to 2016-17). People who took overdoses of paracetamol in single ingredient preparations. Annual numbers of reported paracetamol-related poisonings, hospital admissions, and deaths; number of tablets taken in overdoses. The NHMD included 95668 admissions with paracetamol poisoning diagnoses (2007-08 to 2016-17); the annual number of cases increased by 44.3% during the study period (3.8% per year; 95% CI, 3.2-4.6%). Toxic liver disease was documented for 1816 of these patients; the annual number increased by 108% during the study period (7.7% per year; 95% CI, 6.0-9.5%). The NSWPIC database included 22997 reports of intentional overdose with paracetamol (2004-2017); the annual number increased by 77.0% during the study period (3.3% per year; 95% CI, 2.5-4.2%). The median number of tablets taken increased from 15 (IQR, 10-24) in 2004 to 20 (IQR, 10-35) in 2017. Modified release paracetamol ingestion report numbers increased 38% between 2004 and 2017 (95% CI, 30-47%). 126 in-hospital deaths were recorded in the NHMD, and 205 deaths (in-hospital and out of hospital) in the NCIS, with no temporal trends. The frequency of paracetamol overdose-related hospital admissions has increased in Australia since 2004, and the rise is associated with greater numbers of liver injury diagnoses. Overdose size and the proportion of overdoses involving modified release paracetamol have each also increased.