Acute Acetaminophen Research Articles

Splicing Factor SLU7 Prevents Oxidative Stress-Mediated Hepatocyte Nuclear Factor 4α Degradation, Preserving Hepatic Differentiation and Protecting From Liver Damage.

Hepatocellular dedifferentiation is emerging as an important determinant in liver disease progression. Preservation of mature hepatocyte identity relies on a set of key genes, predominantly the transcription factor hepatocyte nuclear factor 4α (HNF4α) but also splicing factors like SLU7. How these factors interact and become dysregulated and the impact of their impairment in driving liver disease are not fully understood. Expression of SLU7 and that of the adult and oncofetal isoforms of HNF4α, driven by its promoter 1 (P1) and P2, respectively, was studied in diseased human and mouse livers. Hepatic function and damage response were analyzed in wild-type and Slu7-haploinsufficient/heterozygous (Slu7+/- ) mice undergoing chronic (CCl4 ) and acute (acetaminophen) injury. SLU7 expression was restored in CCl4 -injured mice using SLU7-expressing adeno-associated viruses (AAV-SLU7). The hepatocellular SLU7 interactome was characterized by mass spectrometry. Reduced SLU7 expression in human and mouse diseased livers correlated with a switch in HNF4α P1 to P2 usage. This response was reproduced in Slu7+/- mice, which displayed increased sensitivity to chronic and acute liver injury, enhanced oxidative stress, and marked impairment of hepatic functions. AAV-SLU7 infection prevented liver injury and hepatocellular dedifferentiation. Mechanistically we demonstrate a unique role for SLU7 in the preservation of HNF4α1 protein stability through its capacity to protect the liver against oxidative stress. SLU7 is herein identified as a key component of the stress granule proteome, an essential part of the cell's antioxidant machinery. Our results place SLU7 at the highest level of hepatocellular identity control, identifying SLU7 as a link between stress-protective mechanisms and liver differentiation. These findings emphasize the importance of the preservation of hepatic functions in the protection from liver injury.

Point-of-Care Testing and N-Acetylcysteine for Acute Acetaminophen Overdose


 Evidence on the clinical utility and cost-effectiveness of point-of-care devices could not be identified.
 Two evidence-based guidelines recommend a 2-bag regimen of N-acetylcysteine, consisting of both a loading dose and maintenance dose, administered by IV for patients with acute acetaminophen overdose.

Laboratory analysis of acute acetaminophen overdose patients in Emergency Medical Centers: including analysis of one toxicological laboratory data

Purpose: Acetaminophen (APAP) is a widely available drug responsible for a large part of drug-induced hepatotoxicity in developed countries. Although acetaminophen overdose cases in Korea are being continuously reported, there are no reports related to the level of this drug in the patient's blood or of laboratory analysis at emergency departments (ED). This study sought to analyze the acetaminophen overdose cases at a toxicological laboratory and to survey APAP analysis services offered at select EDs. Methods: We analyzed the demographic and analytic data at a toxicological laboratory run by the National Emergency Medical Center (NMC) in 2019-2020. We surveyed the APAP laboratory service in the 38 regional emergency medical centers (EMCs) and 68 local EMCs near the toxicological laboratory. Results: We studied 175 acute poisoning cases (112 women) with positive blood APAP results (mean age 47.0±24.1 years). Suicide attempts comprised 40.0% of the cases and 30.3% APAP overdose events. In the univariate analysis, we observed that patients were significantly younger, with fewer underlying medical diseases. There were a higher number of APAP overdose events, more favorable initial mental status, more toxic quantity intake in the above treatment line group (p<0.05), In multivariate analysis, the toxic amount intake was significantly more frequent in the above treatment line group (p<0.01). Hospital APAP analysis services were available in six EMCs (3/38 regional and 3/68 local). The hospital blood APAP level reporting intervals were shorter than outside-hospital laboratory services (p<0.01, regional 7.0±3.0 vs. 40.6±27.5, local 5.3±3.1 vs. 57.9±45.1 hours). The NMC toxicological laboratory reporting interval was shorter than the other outside-hospital laboratories (p<0.01, regional 5.7±0.6 vs. 50.2±22.7 local 7.5±3.0 vs. 70.5±41.5 hours). Conclusion: Over the treatment line group, toxic amount intake was significantly more frequent. Only six of 106 EMCs have their own APAP analysis service in their hospitals.

The Role of Hypoxia-Induced Mitogenic Factor in Organ-Specific Inflammation in the Lung and Liver: Key Concepts and Gaps in Knowledge Regarding Molecular Mechanisms of Acute or Immune-Mediated Liver Injury

Hypoxia-induced mitogenic factor (HIMF), which is also known as resistin-like molecule α (RELM-α), found in inflammatory zone 1 (FIZZ1), or resistin-like alpha (retlna), is a cysteine-rich secretory protein and cytokine. HIMF has been investigated in the lung as a mediator of pulmonary fibrosis, inflammation and as a marker for alternatively activated macrophages. Although these macrophages have been found to have a role in acute liver injury and acetaminophen toxicity, few studies have investigated the role of HIMF in acute or immune-mediated liver injury. The aim of this focused review is to analyze the literature and examine the effects of HIMF and its human homolog in organ-specific inflammation in the lung and liver. We followed the guidelines set by PRISMA in constructing this review. The relevant checklist items from PRISMA were included. Items related to meta-analysis were excluded because there were no randomized controlled clinical trials. We found that HIMF was increased in most models of acute liver injury and reduced damage from acetaminophen-induced liver injury. We also found strong evidence for HIMF as a marker for alternatively activated macrophages. Our overall risk of bias assessment of all studies included revealed that 80% of manuscripts demonstrated some concerns in the randomization process. We also demonstrated some concerns (54.1%) and high risk (45.9%) of bias in the selection of the reported results. The need for randomization and reduction of bias in the reported results was similarly detected in the studies that focused on HIMF and the liver. In conclusion, we propose that HIMF could be utilized as a marker for M2 macrophages in immune-mediated liver injury. However, we also detected the need for randomized clinical trials and additional experimental and human prospective studies in order to fully comprehend the role of HIMF in acute or immune-mediated liver injury.

Effect of Hydroalcoholic Root Extract of Aerva lanata on Acetaminophen Induced Hepatotoxicity in Wistar Rats

Introduction: Acute acetaminophen poisoning leads to fulminant hepatic failure and renal tubular damage. N-Acetyl Cysteine (NAC), an antidote for acetaminophen poisoning, carries its own adverse effect profile such as anaphylactoid reactions, cerebral oedema and hyponatremia at high doses. Aerva lanata, an erect or prostate herbaceous weed has a wide range of medicinal uses like, hepatoprotection, nephroprotection, antiasthamatic and antiamoebic. Previous study on rats have shown that hydroalcoholic root extract of Aerva lanata has significant hepatoprotective property when administered before acetaminophen. Aim: To evaluate the effect of hydroalcoholic root extract of Aerva lanata and NAC, as monotherapy and in combination, for acetaminophen induced hepatotoxicity in albino Wistar rats. Materials and Methods: This was an experimental animal study. Thirty adult male albino Wistar rats were equally divided into five groups: group I-vehicle, group II-acetaminophen only, group III- acetaminophen+NAC, group IV-acetaminophen+Aerva lanata root extract, group V-Acetaminophen+NAC+Aerva lanata root extract. Hepatotoxicity was induced in rats belonging to groups II, III, IV and V using acetaminophen (2 g/kg p.o). All rats were sacrificed after 72 hours of drug administration, blood samples were sent for biochemical analysis. Liver and kidney samples were sent for histopathological studies. Results were analysed using one-way ANOVA followed by post hoc Dunnett t-test. Results: Root extract of Aerva lanata significantly reduces the liver enzyme markers Aspartate Transaminase (AST), Alanine Transaminase (ALT), Gamma Glutamyl Transferase (GGT) and bilirubin) and blood urea concentration. The combination therapy (root extract with NAC) showed a highly significant decrease in AST, ALT, GGT (p<0.001), bilirubin (p<0.01) and blood urea (p<0.001) when compared with the paracetamol group. A significant reversal of liver injury was seen in histopathological studies. Conclusion: The combination therapy showed better improvement of liver enzyme and renal parameters, along with significant improvement in histopathological changes. Hence, combination of hydroalcoholic root extract of Aerva lanata along with NAC can be effective in treating acetaminophen poisoning.

Factors of Determining N-acetylcysteine Administration in Patients with Acute Acetaminophen Poisoning

Purpose: In acute acetaminophen poisoning, the administration of N-acetylcysteine (NAC) can effectively treat the main complications, such as kidney injury and liver failure. In the current situation, measurements of the acetaminophen concentration are not checked in the usual medical facilities. Therefore, this study examined the factors of determining the administration of NAC in addition to the stated amount of intake. Methods: The medical records of patients who visited Ajou University Hospital emergency center with acetaminophen poisoning from January 2015 to December 2019 were reviewed retrospectively. One hundred and seventy-nine patients were initially included. Among these patients, 82 patients were finally selected according to the inclusion criteria in the study. The inclusion criteria were as follows: patients who were 15 years of age or older; those whose ingested dose, ingested time, and body weight were clearly identified; and patients whose acetaminophen sampling time was within 24 hours. Patients were divided into two groups: NAC administered vs. non-NAC administered. The following variables were compared in these two groups: ingested dose, ingested dose per body weight, hospital arrival time after ingestion, suicide attempt history, psychiatric disease history, classification of toxic/non-toxic groups, duration of hospitalization, and laboratory results. Results: Univariate analysis revealed the ingested dose per body weight, hospital arrival time after ingestion, suicide attempt history, and psychiatric disease history to be the determining factors in administering NAC. Logistic regression analysis confirmed that the ingested dose per body weight was the only significant factor leading to an NAC treatment decision. (Odds ratio=1.039, 95% Confidential interval=1.009-1.070, p=0.009) Conclusion: The ingested dose per body weight was the only determining factor for administering NAC in patients with acute acetaminophen poisoning. On the other hand, additional criteria or indicators for the NAC administration decision will be necessary considering the inaccuracy of the ingested dose per body weight and the efficiency of NAC administration.

Effects of acetaminophen on risk taking.

Acetaminophen, an analgesic and antipyretic available over-the-counter and used in over 600 medicines, is one of the most consumed drugs in the USA. Recent research has suggested that acetaminophen’s effects extend to the blunting of negative as well as positive affect. Because affect is a determinant of risk perception and risk taking, we tested the hypothesis that acute acetaminophen consumption (1000 mg) could influence these important judgments and decisions. In three double-blind, placebo-controlled studies, healthy young adults completed a laboratory measure of risk taking (Balloon Analog Risk Task) and in Studies 1 and 2 completed self-report measures of risk perception. Across all studies (total n = 545), acetaminophen increased risk-taking behavior. On the more affectively stimulating risk perception measure used in Study 2, acetaminophen reduced self-reported perceived risk and this reduction statistically mediated increased risk-taking behavior. These results indicate that acetaminophen can increase risk taking, which may be due to reductions in risk perceptions, particularly those that are highly affect laden.

Glutathione S-Transferase (A1) as a marker of Acute Acetaminophen Induced Hepatotoxicity and Nephrotoxicity, and the Protective Role of Dexmedetomidine

Glutathione S-Transferase (A1) as a marker of Acute Acetaminophen Induced Hepatotoxicity and Nephrotoxicity, and the Protective Role of Dexmedetomidine

Cell-permeable succinate prodrugs rescue mitochondrial respiration in cellular models of acute acetaminophen overdose.

Acetaminophen is one of the most common over-the-counter pain medications used worldwide and is considered safe at therapeutic dose. However, intentional and unintentional overdose accounts for up to 70% of acute liver failure cases in the western world. Extensive research has demonstrated that the induction of oxidative stress and mitochondrial dysfunction are central to the development of acetaminophen-induced liver injury. Despite the insight gained on the mechanism of acetaminophen toxicity, there still is only one clinically approved pharmacological treatment option, N-acetylcysteine. N-acetylcysteine increases the cell's antioxidant defense and protects liver cells from further acetaminophen-induced oxidative damage. Because it primarily protects healthy liver cells rather than rescuing the already injured cells alternative treatment strategies that target the latter cell population are warranted. In this study, we investigated mitochondria as therapeutic target for the development of novel treatment strategies for acetaminophen-induced liver injury. Characterization of the mitochondrial toxicity due to acute acetaminophen overdose in vitro in human cells using detailed respirometric analysis revealed that complex I-linked (NADH-dependent) but not complex II-linked (succinate-dependent) mitochondrial respiration is inhibited by acetaminophen. Treatment with a novel cell-permeable succinate prodrug rescues acetaminophen-induced impaired mitochondrial respiration. This suggests cell-permeable succinate prodrugs as a potential alternative treatment strategy to counteract acetaminophen-induced liver injury.

The Unexpected Role of Neutrophils for Resolving Liver Inflammation by Transmitting MicroRNA-223 to Macrophages.

Neutrophils are commonly recognized as prototypic inflammatory cells: They invade the liver upon injury, have a short half-life in inflamed tissue and aggravate injury as well as inflammatory reactions. This has been conclusively demonstrated for acute acetaminophen injury in mice, where myeloid-cell specific receptor for advanced glycation end products (RAGE)-deficiency dramatically altered neutrophil recruitment to necrotic areas, and high-mobility group box 1 (HMGB1) epithelial cell deficiency in the liver prevented all acetaminophen-induced mortality. This article is protected by copyright. All rights reserved.

Acute acetaminophen toxicity in adults.

When taken in the recommended dosage, acetaminophen is a safe and effective analgesic and antipyretic agent. Its wide availability and easy accessibility make accidental or intentional overdose, leading to hepatotoxicity, a common occurrence. To prevent morbidity and mortality, prompt recognition of acetaminophen toxicity is essential. This article covers the stages of acetaminophen toxicity, recommended treatments, and NP considerations, including patient education recommendations.

Acute acetaminophen intoxication induces direct neurotoxicity in rats manifested as astrogliosis and decreased dopaminergic markers in brain areas associated with locomotor regulation

Acetaminophen (APAP) administration at therapeutic doses is safe, however overdosing produces hepatocellular injury via a multifactorial mechanism(s) that involves generation of reactive oxygen species (ROS), being the most common cause of acute liver failure (ALF) in the northern hemisphere. Brain alterations induced by APAP intoxication are usually considered secondary to hepatic encephalopathy development due to ALF. Although APAP is primarily metabolized in the liver, it is also distributed and metabolized homogeneously in the brain, affecting brain redox status. Nevertheless, comprehensive studies on the potential of APAP intoxication to produce brain toxicity are scarce. The aim of this study was to characterize the direct toxic effects of APAP in different regions of the brain and on behavior in rats where the magnitude of hepatotoxicity produced is not associated with ALF.The present work demonstrates that APAP intoxication producing hepatotoxicity, but not ALF in rats, is associated with marked hypolocomotion. Our studies also suggest that selective downregulation in dopamine levels in brain areas that regulate motor activity may be responsible, in part, for the decreased locomotion observed with APAP treatment. Furthermore, we observed that the brain histoarchitecture is conserved and that edema is not present. However, an increase in oxidative stress, reactive astrogliosis and a decrease in neuron processes are the main features observed in APAP-intoxicated animals. These effects might be partly due to direct toxic effects of APAP in brain, since the same reactive astrogliosis observed in rats was also observed in rat primary astrocyte cultures exposed to APAP.

Acute acetaminophen toxicity in adults

When taken in the recommended dosage, acetaminophen is a safe and effective analgesic and antipyretic agent. Its wide availability and easy accessibility make accidental or intentional overdose, leading to hepatotoxicity, a common occurrence. To prevent morbidity and mortality, prompt recognition of acetaminophen toxicity is essential. This article covers the stages of acetaminophen toxicity, recommended treatments, and NP considerations, including patient education recommendations.

Elevation of Procalcitonin in an Adolescent Acetaminophen Intoxication

Procalcitonin (PCT) is commonly employed in medical practice as a diagnostic biomarker of bacterial infection and also as a monitoring biomarker for antimicrobial therapy. There have been a few published reports concerning elevated PCT levels in people with acute liver injury caused by an overdose of acetaminophen. We report here on a case of PCT elevation in an adolescent with acute acetaminophen poisoning without any bacterial infection or liver injury. A 15-year-old girl had deliberately ingested 20 tablets of 650 mg acetaminophen (13 g) and she presented to our emergency department. The PCT level on admission was elevated to 65.64 ng/mL (reference range: 0-0.5 ng/mL). Her PCT level on the second day peaked up to 100 ng/mL and then it gradually decreased. There was no evidence of liver injury or infection on the computed tomography examination and other lab tests. The patient regained her good health and was discharged on the sixth day of hospitalization.

Ameliorative Effect of Cimetidine and Silymarin on Acute Acetaminophen-induced Hepatotoxicity in Adult Albino Rats: An Experimental Comparative Study

Acetaminophen is an analgesic and antipyretic drug, its overdose cause hepatotoxicity. The current antidote for acetaminophen hepatotoxicity is N-acetyl cysteine (NAC); however, NAC has been resulted in severe side effects as seizures, intracranial hypertension and cerebral edema. This study aimed to assess and compare the ameliorative effects of cimetidine and silymarin against acute acetaminophen–induced hepatotoxicity. Fifty four adult albino rats were divided into nine groups: negative control; solvent control; silymarin control; cimetidine control; cimetidine and silymarin control; acetaminophen group; acetaminophen and silymarin group; acetaminophen and cimetidine group; acetaminophen, cimetidine and silymarin group. A single dose of: acetaminophen (800 mg/kg, orally); silymarin (150mg/kg, orally) and cimetidine (150 mg/kg, intraperitoneally) were given according to study regimen. Liver histopathology, biochemical analysis of liver aminotransferases (AST & ALT) and hepatic tissue levels of oxidative stress index (MDA) and antioxidant (GSH) were assessed. Treatment with cimetidine alone gave better biochemical results as compared to treatment with silymarin alone. However combined treatment with cimetidine and silymarin showed better ameliorative effects than either of them given alone, evidenced by better improvement in histopathological examination and biochemical results as compared to other tested groups, and these results were non-significant as compared to controls. In conclusion treatment with silymarin and cimetidine in-combination for acute acetaminophen–induced hepatotoxicity showed better improvement probably due to synergistic hepatoprotective effects.

Contralateral fatigue during severe-intensity single-leg exercise: influence of acute acetaminophen ingestion.

Exhaustive single-leg exercise has been suggested to reduce time to task failure (Tlim) during subsequent exercise in the contralateral leg by exacerbating central fatigue development. We investigated the influence of acetaminophen (ACT), an analgesic that may blunt central fatigue development, on Tlim during single-leg exercise completed with and without prior fatiguing exercise of the contralateral leg. Fourteen recreationally active men performed single-leg severe-intensity knee-extensor exercise to Tlim on the left (Leg1) and right (Leg2) legs without prior contralateral fatigue and on Leg2 immediately following Leg1 (Leg2-CONTRA). The tests were completed following ingestion of 1-g ACT or maltodextrin [placebo (PL)] capsules. Intramuscular phosphorus-containing metabolites and substrates and muscle activation were assessed using 31P-MRS and electromyography, respectively. Tlim was not different between Leg1ACT and Leg1PL conditions (402 ± 101 vs. 390 ± 106 s, P = 0.11). There was also no difference in Tlim between Leg2ACT-CONTRA and Leg2PL-CONTRA (324 ± 85 vs. 311 ± 92 s, P = 0.10), but Tlim was shorter in Leg2ACT-CONTRA and Leg2PL-CONTRA than in Leg2CON (385 ± 104 s, both P < 0.05). There were no differences in intramuscular phosphorus-containing metabolites and substrates or muscle activation between Leg1ACT and Leg1PL and between Leg2ACT-CONTRA and Leg2PL-CONTRA (all P > 0.05). These findings suggest that levels of metabolic perturbation and muscle activation at Tlim are not different during single-leg severe-intensity knee-extensor exercise completed with or without prior fatiguing exercise of the contralateral leg. Despite contralateral fatigue, ACT ingestion did not alter neuromuscular responses, muscle metabolites, or exercise performance.

5-Oxoproline concentrations in acute acetaminophen overdose

Introduction: Several reports describe high anion gap metabolic acidosis with 5-oxoproline (5-OP) after acetaminophen exposure, including therapeutic use of acetaminophen. The mechanism may involve disordered glutathione metabolism. It is unknown whether acute acetaminophen overdose consistently causes elevations in 5-oxoproline concentration.Methods: We enrolled 23 consecutive adult and adolescent patients with measureable plasma APAP after acute APAP overdose. We used plasma left over in the laboratory after blood tests obtained in clinical care of the patients. We measured plasma [5-OP] by GC/MS. We compared the [5-OP] to laboratory results obtained in the care of these patients to search for correlations. The study had IRB approval.Results: Eighteen patients had non-detectable or normal (<100 μmol/L) 5-oxoproline concentrations. Six more patients had concentrations between 100 μmol/L and 300 μmol/L. There was no significant correlation of 5-OP with APAP, AST, ALT, creatinine, anion gap, INR, or total bilirubin.Discussion: Limitations of the study include small sample size and treatment with IV N-acetylcysteine for all patients with APAP concentrations above the 150 line of the Rumack Matthew nomogram or with hepatotoxicity. We believe that inherited enzyme deficiencies more likely explain cases of 5-oxoprolinemia.Conclusion: Acetaminophen overdose generally results in normal 5-oxoproline concentrations with some patients having slightly elevated 5-oxoproline concentrations.

Hematoprotective effects and antioxidant properties of β-glucan and vitamin C against acetaminophen-induced toxicity: an experimental study in rats

Acetaminophen is widely used as an over-the-counter analgesic and antipyretic drug. The aim of the present study was to investigate the pro-oxidative effects of acetaminophen (300 mg/kg/day i.p.) and antioxidative effects of β-glucan (4 mg/kg/day i.p.) and/or vitamin C (100 mg/kg/day i.p.) on the blood parameters of treated rats. After 3 days of treatment, hematological and parameters of redox status were measured. Exposure of rats to acetaminophen caused significant changes in some hematological parameters and the glutathione redox cycle, leading to an increased concentration of oxidative stress parameters and the formation of lipid peroxidation, while the activities of antioxidant enzymes were decreased. Administration of β-glucan and/or vitamin C reduced lipid peroxidation and restored the levels of examined hematological and oxidative stress parameters and improved the activities of antioxidant enzymes. Obtained results demonstrated that acetaminophen has significant pro-oxidative effects and may disrupt redox balance in blood of rats, while the combination of β-glucan and/or vitamin C amplified the antioxidant defense potential and exhibited a strong hematoprotective activity against acetaminophen-induced toxicity. Therefore, β-glucan and vitamin C co-treatment may be a promising therapeutic option for the treatment of acute acetaminophen hematotoxicity.

Changing nomogram risk zone classification with serial testing after acute acetaminophen overdose: a retrospective database analysis

Context: The Rumack–Matthew nomogram stratifies patients into discrete risk zones following acetaminophen (APAP) overdose. Treatment decisions have traditionally been based on the initial risk zone. “Line-crossing” between zones occurs and is poorly understood. The study objective was to characterize line-crossing behavior in acute APAP overdose patients, especially moving from below to above the nomogram treatment threshold.Methods and materials: The study was a secondary analysis of the Canadian Acetaminophen Overdose Study (CAOS) database, a large medical record review of patients hospitalized in eight large Canadian cities (1980–2005) following APAP poisoning. Population consisted of acute APAP overdose patients with at least two serum concentrations performed during hospitalization. Using ordinal logistic regression, we studied the effects of patient demographics, ingestion size/timing, APAP concentrations, time to N-acetylcysteine (NAC), and co-ingestants on a three-level dependent variable: patients whose risk increased two or more zones, those remaining in the same or adjacent zone, and those whose risk fell by two or more zones.Results: Of the 3201 eligible hospitalizations with 7705 APAP concentrations, half (1679, 52.5%) crossed at least one zone (up or down) within 24 h of acute ingestion, including 190 (5.9%), who crossed at least two lines into a higher risk zone, and 516 (16.1%) at least two lines into a lower risk zone. Of the 1251 patients initially below the nomogram treatment line of 150 μg/mL, 131 (10.8%) patients crossed above this line. Being older, male, and co-ingesting opioids, antimuscarinics, or NSAIDs were independently associated with line-crossing.Conclusions: Patients commonly crossed nomogram risk zones, including from below to above the current treatment threshold. These findings support recommendations for serial APAP testing until the individual risk of hepatic injury is clearly established.

Acute acetaminophene-induced hepatotoxicity and nephrotoxicity; therapeutic effect of dexmedetomidine

Acute acetaminophen (APAP) overdose has been shown to cause toxicity and the primary treatment medication is N-acetylcysteine (NAC). Dexmedetomidine (DEX) is a sedative drug with known antioxidant properties. We researched whether DEX has an injury-reducing effect on toxicity. Rats were divided into: Group I (control), Group II (APAP) Group III (NAC) Group IV (DEX) and Group V (NAC+DEX). Histopathologic investigations of tissues were performed and glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA), myeloperoxidase (MPO) and beta trace protein (PGD2S) levels were studied in blood samples. DEX administration for hepatotoxicity and nephrotoxicity induced with APAP, caused a significant reduction in oxidative injury markers like MDA and MPO, a significant increase in GSH-Px level and a significant degree of amelioration in liver histopathologic scores. DEX administration for APAP toxicity causes a reduction in oxidative injury biomarkers, increased antioxidant biomarker levels and significant reduction in liver histopathologic scores. The beneficial effect of DEX use for detection of toxicity induced by acute APAP overdose, was shown in this study for the first time (Tab. 5, Fig. 2, Ref. 41).