Acetaminophen Group Research Articles

Pharmacokinetics and effects of codeine in combination with acetaminophen on thermal nociception in horses.

Codeine and acetaminophen in combination have proven to be an effective analgesic treatment for moderate-to-severe and postoperative pain in humans. Studies have demonstrated that codeine and acetaminophen, when administered as sole agents, are well tolerated by horses. In the current study, we hypothesized that administration of the combination of codeine and acetaminophen would result in a significant thermal antinociceptive effect compared with administration of either alone. Six horses were administered oral doses of codeine (1.2 mg/kg), acetaminophen (20 mg/kg), and codeine plus acetaminophen (1.2 mg/kg codeine and 6-6.4 mg/kg acetaminophen) in a three-way balanced crossover design. Plasma samples were collected, concentrations of drug and metabolites determined via liquid chromatography-mass spectrometry, and pharmacokinetic analyses were performed. Pharmacodynamic outcomes, including effect on thermal thresholds, were assessed. Codeine Cmax and AUC were significantly different between the codeine and combination group. There was considerable inter-individual variation in the pharmacokinetic parameters for codeine, acetaminophen, and their metabolites in horses. All treatments were well tolerated with minimal significant adverse effects. An increase in the thermal threshold was noted at 1.5 and 2 h, from 15 min through 6 h and 0.5, 1, 1.5, and 3 h in the codeine, acetaminophen, and combination groups, respectively.

Efficacy of Intravenous Ibuprofen and Acetaminophen on Postoperative Pain and Tramadol Consumption in Laparoscopic Cholecystectomy: Prospective, Randomized, Double-blinded Clinical Trial

Background: Many techniques, including multimodal analgesia, have been used to manage postoperative pain after laparoscopic cholecystectomy (LC). Although the number of studies using intravenous ibuprofen (IV) is still limited, ibuprofen has been shown to have a potential role in managing postoperative pain. The primary outcome of this study is to evaluate and compare the impact of IV forms of ibuprofen and acetaminophen on 24-hour postoperative opioid consumption and pain management in patients undergoing LC. The second outcome of the study is to evaluate the impact of ibuprofen and acetaminophen on opioid-related adverse events (ORAE).
 Materials and Methods: This study was a prospective, randomized, double-blind clinical trial. Following ethical committee approval, 70 patients aged 18 to 65, American Society of Anesthesiology (ASA) score I- II, and those scheduled for LC were enrolled in the study. Patients were randomly divided into two groups. The control group (n=35) received 800 mg IV ibuprofen (group I) in 100 mL saline during surgery, while the acetaminophen group (n=35) received 1000 mg (group A). In the postoperative period, all patients received a patient-controlled analgesia (PCA) device with tramadol. The PCA device was set to a bolus dose of 10 mg and had a lockout time of 15 minutes. A blinded pain nurse assessed postoperative analgesia at 1, 2, 4, 6, 12, and 24 hours using a numerical rating scale (NRS). The incidence of postoperative nausea and vomiting (PONV), total tramadol consumption, and the need for additional analgesics during the 24-hour postoperative period were recorded.
 Results: Seventy patients who underwent LC participated in this study. The use of analgesic medications was statistically lower in group I than in the other group A. NRS scores between the IV ibuprofen and acetaminophen groups were statistically similar at 1, 2, 4, 6, 12, and 24 hours postoperatively (P>0.05). 24-hour opioid consumption was statistically significantly higher in group A than in group I (P0.05). PONV rates were similar in the ibuprofen and acetaminophen groups (P>0.05). ORAEs were similar between groups.
 Conclusion: Ibuprofen as part of tramadol-based multimodal analgesia reduced tramadol consumption compared to acetaminophen during the first 24 hours postoperatively following elective LC surgery. The IV ibuprofen-tramadol combination appeared superior to an acetaminophen-tramadol combination. ORAEs were similar in both groups.

Acetaminophen changes Mu rhythm power related to pain empathy

Empathy is an intricate ability that entails the subjective feeling and understanding of emotions someone else may be experiencing. Acetaminophen, the active ingredient found in Tylenol, is among the most common pain medications consumed. There is new evidence, however, that suggests this common analgesic may also dampen empathic processes. However, no previous study has investigated the effect acetaminophen may have on pain empathy or mu power during a pain empathy task. Therefore, participants were randomly assigned to either an experimental (acetaminophen) or control (sugar) group in a double-blinded experimental research design aimed to measure mu power, using EEG, and behavioral responses to painful and non-painful images. Participants in the experimental group were administered 1000 mg of acetaminophen, and it was verified that participants were unaware of their group assignment. We found that mu suppression was greater in the acetaminophen group, which was strongest at electrode C3. Additionally, mu power differences between painful and non-painful images were related to trait empathy, and mu power during the painful images was positively correlated with empathy behavioral rating scores. Results from this study suggest that in addition to reducing physical pain, acetaminophen may also change the neural response when perceiving others in pain. The implications of these findings could possibly lead to changes in how we prescribe and administer this common drug.

Serious Clinical Outcomes of COVID-19 Related to Acetaminophen or NSAIDs from a Nationwide Population-Based Cohort Study

Acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) have been widely prescribed to infected patients; however, the safety of them has not been investigated in patients with serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our objective was to evaluate the association between the previous use of acetaminophen or NSAIDs and the clinical outcomes of SARS-CoV-2 infection. A nationwide population-based cohort study was conducted using the Korean Health Insurance Review and Assessment Database through propensity score matching (PSM). A total of 25,739 patients aged 20 years and older who tested for SARS-CoV-2 were included from 1 January 2015 to 15 May 2020. The primary endpoint was a positive result for a SARS-CoV-2 test, and the secondary endpoint was serious clinical outcomes of SARS-CoV-2 infection, such as conventional oxygen therapy, admission to the intensive care unit, need for invasive ventilation care, or death. Of 1058 patients, after propensity score matching, 176 acetaminophen users and 162 NSAIDs users were diagnosed with coronavirus disease 2019. After PSM, 162 paired data sets were generated, and the clinical outcomes of the acetaminophen group were not significantly different from those of the NSAIDs group. This suggests that acetaminophen and NSAIDs can be used safely to control symptoms in patients suspected of having SARS-CoV-2.

Efficacy and feasibility of scheduled intravenous acetaminophen administration after pancreatoduodenectomy: a propensity score-matched study.

The efficiency and safety of routine intravenous administration of acetaminophen after highly invasive hepatobiliary pancreatic surgery remain unclear. In particular, there have been no studies focusing on pancreatoduodenectomy. The present study clarified its clinical utility for patients undergoing pancreatoduodenectomy. We retrospectively collected 179 patients who underwent open pancreatoduodenectomy from 2015 to 2020. The analgesic effects and adverse events in patients with scheduled intravenous administration of acetaminophen were evaluated using propensity score matching. After 40 patients from each group were selected by propensity score matching, the postoperative liver function tests were not significantly different between the control and acetaminophen groups. No significant differences were found in the self-reported pain intensity score or postoperative nausea and vomiting; however, the rate of pentazocine use and the total number of additional analgesics were significantly lower in the acetaminophen group than in the control group (p = 0.003 and 0.002, respectively). The scheduled intravenous administration of acetaminophen did not affect the postoperative liver function and had a good analgesic effect after pancreatoduodenectomy.

Evaluation of the Effect of Common Analgesics on Pulpal Sensibility Tests: A Clinical Trial

IntroductionAccurate diagnosis is one of the most important steps before endodontic treatment. The aim of this study was to assess the effect of 2 commonly used analgesics namely ibuprofen and acetaminophen on the cold and electric pulp test (EPT) results in participants with symptomatic irreversible pulpitis (SIP). MethodsThis clinical trial evaluated 41 participants with pain due to SIP. The cold test and EPT were performed for teeth with SIP, and also for the corresponding tooth with healthy pulp in the contralateral quadrant. The participants then received 500 mg acetaminophen, 400 mg ibuprofen, or the placebo in the 3 groups. The cold test and EPT were repeated at 20, 40, and 60 minutes after medication intake, and the results were compared with the pretreatment values. ResultsIn the acetaminophen group, the results of cold test significantly decreased 40 (P < .05), and 60 (P < .05) minutes after analgesic intake in teeth with SIP and after 40 minutes (P < .05) in the corresponding contralateral teeth with healthy pulp. In the ibuprofen group, the cold test results significantly decreased at 20 (P < .05), 40 (P < .05), and 60 (P < .05) minutes after analgesic intake in teeth with SIP and after 40 minutes (P < .05) in the corresponding contralateral teeth with healthy pulp. The EPT results were not significantly affected by the studied analgesics at any time point (P > .05). There was no significant difference among the study groups regarding sex (P > .05). ConclusionIt appears that both acetaminophen and ibuprofen can affect the pulpal response to the cold sensibility test. However, the studied medications had no significant effect on the EPT results. Therefore, dental clinicians should be aware of the possible effects of such medications on the cold test response.

Potential Curative Effects of Aqueous Extracts of Cissus quadrangularis (Vitaceae) and Jatropha gossypiifolia (Euphorbiaceae) on Acetaminophen-Induced Liver Injury in Mice

Acetaminophen-induced liver injury remains a significant public health problem because available treatments are limited due to their adverse effects. Medicinal plants, which are an important source of bioactive molecules, could be an alternative treatment for liver disease. This study was designed to investigate the curative effect of aqueous extracts of Cissus quadrangularis (Vitaceae) and Jatropha gossypiifolia (Euphorbiaceae) on acetaminophen-induced liver injury in mice. Mice were divided into groups and treated with distilled water, silymarin (50 mg/kg), a reference hepatoprotective agent, and aqueous extracts of C quadrangularis and J gossypiifolia (50 and 100 mg/kg, PO, respectively). These substances were given as a single daily dose 4 hours after acetaminophen administration (300 mg/kg, PO) for 2 days. Mice were humanely put to death 24 hours after the last dose and serum alanine aminotransferase and aspartate aminotransferase activities, total bilirubin and protein levels, reduced glutathione, superoxide dismutase, malondialdehyde, catalase, and nitrite tissue levels were assessed. Histology of the livers of the mice was performed by hematoxylin and eosin staining. Acetaminophen administration induced a significant (P < 0.05) mean (SEM) body weight loss (-14.45% [5.92%]), a significant elevation of alanine aminotransferase activity (15.08%), total protein and bilirubin levels (25.80%), and a significant (P < 0.05) increase in liver superoxide dismutase (67.71%), catalase (63.00%), glutathione (40.29%), malondialdehyde (30.67%), and nitrite levels compared with the control group. In curative treatment, C quadrangularis and J gossypiifolia (50 and 100 mg/kg) significantly (P < 0.05) reduced mean (SEM) body weight loss (16.67% [7.16%] and 1.25% [0.51%], respectively), serum alanine aminotransferase activity (17.62% and 11.14%, respectively), bilirubin level (29.62% and 49.14%, respectively) compared with acetaminophen group, and J gossypiifolia normalized serum total protein level. Both extracts significantly (P < 0.05) reduced the levels of glutathione and malondialdehyde and normalized that of nitrite, superoxide dismutase, and catalase compared with the acetaminophen group. Hepatocyte necrosis and inflammatory cell infiltration were remarkably reduced by the plant extracts. The results obtained are evidence in favor of the development of a formulation based on the extracts of these plants against liver diseases.

Comparative Study of the Effect of Indomethacin and Acetaminophen on Pain after Collagen Cross-Linking Surgery

Introduction: One of the surgeries that needs to be considered after pain and discomfort is corneal cross-linking of the cornea. The aim of this study was to compare the effect of indomethacin and acetaminophen oral surgery before surgery on postoperative pain in the patients undergoing collagen cross-linking surgery.&#x0D; Methods: The present study was a double-blind clinical trial study that was performed on all the patients undergoing collagen cross-linking surgery. Fifty patients were divided into two groups of 25 patients receiving acetaminophen 500 mg and indomethacin 75 mg before surgery. VAS scale was used to determine the severity of pain. Data were collected through a pain questionnaire and statistically analyzed using SPSS16 software.&#x0D; Results: In the acetaminophen group, 60% were female and 40% male, and in the indomethacin group, 64% were female and 36% male, which were similar in terms of gender. The mean age in the acetaminophen group was 24.28±5 and in the indomethacin group was 24.04±4. The two groups were similar in the case of age. Based on Visual Analogue Scale (VAS) after collagen cross-linking surgery, the pain intensity was 6.29 in the acetaminophen group and 7.61 in the indomethacin group, respectively, which was significantly lower in the acetaminophen group. Moreover, there was no significant difference between the amounts of postoperative pain in the two groups.&#x0D; Conclusion: Oral administration of acetaminophen before corneal cross-linking surgery was more effective in reducing postoperative pain than indomethacin, while there was no difference in the number of postoperative analgesics between the two groups during 24 hours postoperation.

Use of Fever and Pain Medication for Self-Medication at the Talita Pharmacy, Makassar City

Self-medication is part of "self-care" which is an effort to maintain health or prevent and overcome disease. Self-medication is usually done to treat minor illnesses, including fever and pain. The purpose of this study was to find out which class of Fever and Pain drugs were most widely used for self-medication at the Talita Pharmacy, Makassar City. This research method has used descriptive method. The results showed that the most widely used Fever and Pain drug group in January was paracetamol as much as 85.1851%, February as much as 72.27%, March as much as 0.8088%. So it can be concluded that the most widely used class of fever and pain drugs for self-medication at the Talita Pharmacy in Makassar City in January - March 2022 is the Acetaminophen (Paracetamol) group.

Evaluating the correlation between migraine and subclinical atherosclerosis

Backgrounds and aimsMigraine is known to be associated with vascular dysfunction. However, sufficient evidence has not been reported in this regard. This study aims to assess subclinical atherosclerosis and endothelial function via Doppler Sonography in migraine patients. MethodsIn this case control study, Subjects were divided into two groups; Patients with migraine, and Healthy controls. Migraine was diagnosed according to the International Classification of Headache Disorders criteria. Participants were evaluated for carotid intima-media thickness (IMT) and flow-mediated dilation (FMD) indices, and the findings were compared between the two groups. ResultsIn the study population, 64.9 % were female, and the mean age was 34.63 ± 6.06 years. Of the 47 people with migraine, 12 suffered from migraine with aura. Increased IMT was more in migraine with and without aura compared to control (p = 0.247), and FMD was lower in these groups than the control group (p = 0.311). There was a significant correlation between the duration of headache with the duration of migraine (p = 0.007, 0.389) and IMT (p = 0.038, 0.303). No statistically significant differences were observed between NSAID, acetaminophen, and ergotamine groups with IMT (p = 0.532) and FMD (p = 0.834). ConclusionMigraine and its related medications do not affect vascular changes in favor of atherosclerosis. However, these findings might be valid for patients with acute migraines only.

Comparative efficacy of ketamine, lidocaine, acetaminophen, and dexmedetomidine combined with morphine patient-controlled analgesia in treating opium-addicted patients undergoing tibia fracture surgery

Objective: To compare the effect of ketamine, lidocaine, acetaminophen, and dexmedetomidine combined with morphine patient-controlled analgesia for opium addicts after tibial fracture surgery. Methods: This double-blind clinical trial included opium-addicted patients undergoing tibia fracture surgery. Patients were recruited and randomized to four different groups including the ketamine group, the lidocaine group, the acetaminophen group, and the dexmedetomidine group. The hemodynamic parameters such as heart rate (HR), mean arterial pressure, and arterial SaO2, alongside visual analog scale pain scores, sedation assessed by Ramsay score, nausea and vomiting, and opioid use were recorded and compared among the four groups. Results: This study included 140 patients, aged 37 (32, 41) years, with 92 males and 48 females, and each group had 35 patients. Dexmedetomidine-sedated subjects had the lowest blood pressure from 1 to 24 h after surgery, decreased HR at 12 and 24 h after surgery, and more satisfactory sedation (P&lt;0.05). Notwithstanding no significant difference was noted in the pain scores, or nausea and vomiting among the groups (P&gt;0.05). Conclusions: Dexmedetomidine has a better sedation effect compared to ketamine, lidocaine, and acetaminophen for pain control, but the final choice hinges on the patients’ physical condition and the anesthesiologist's preference. Clinical registarion: It is registered in Iranian Registry Clinical Trial by code IRCT20141209020258N146.

Efficacy and safety of intravenous acetaminophen (2g/day) for reducing opioid consumption in Chinese adults after elective orthopedic surgery: A multicenter randomized controlled trial.

Background: Acetaminophen is an important component of a multimodal analgesia strategy to reduce opioid consumption and pain intensity after an orthopedic surgery. The opioid-sparing efficacy of intravenous acetaminophen has been established at a daily dose of 4 g. However, it is still unclear for the daily dose of 2 g of acetaminophen, which is recommended by the China Food and Drug Administration Center for Drug Evaluation, in terms of its efficacy and safety. Objectives: This study aimed to evaluate the efficacy and safety of intravenous acetaminophen at a daily dose of 2 g for reducing opioid consumption and pain intensity after orthopedic surgery. Methods: In this multicenter, randomized, double-blind, placebo-controlled phase III trial, 235 patients who underwent orthopedic surgery were randomly assigned to receive intravenous acetaminophen 500 mg every 6 h or placebo. Postoperative morphine consumption, pain intensity at rest and during movement, and adverse events were analysed. Results: For the mean (standard deviation) morphine consumption within 24 h after surgery, intravenous acetaminophen was superior to placebo both in the modified intention-to-treat analysis [8.7 (7.7) mg vs. 11.2 (9.2) mg] in the acetaminophen group and the placebo group, respectively. Difference in means: 2.5 mg; 95% confidence interval, 0.25 to 4.61; p = 0.030), and in the per-protocol analysis (8.3 (7.0) mg and 11.7 (9.9) mg in the acetaminophen group and the placebo group, respectively. Difference in means: 3.4 mg; 95% confidence interval: 1.05 to 5.77; p = 0.005). The two groups did not differ significantly in terms of pain intensity and adverse events. Conclusion: Our results suggest that intravenous acetaminophen at a daily dose of 2 g can reduce morphine consumption by Chinese adults within the first 24 h after orthopedic surgery, but the extent of reduction is not clinically relevant. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT02811991].

Scheduled intravenous acetaminophen versus continuous intravenous fentanyl in postoperative analgesia following McKeown esophagectomy with thoracotomy and laparotomy: A pilot study

IntroductionTo determine whether the study protocol was appropriate for comparing the analgesic and adverse effects of postoperative fentanyl and acetaminophen transfusion following McKeown esophagectomy. MethodsIn this prospective pilot study, patients who underwent McKeown esophagectomy with right thoracotomy and laparotomy between October 2015 and August 2017 received either continuous intravenous fentanyl (group A) or intravenous acetaminophen (group B) every 6 h. We evaluated pain intensity, number of daily rescue doses, nausea, vigilance, postoperative clinical course, and adverse events postoperatively. ResultsFour patients in group A dropped out owing to severe drowsiness. Pain intensity and number of rescue doses did not differ significantly, and the intensity of nausea was low in both groups. During postoperative days 1–3, vigilance was significantly better in group B (p = 0.004). The median duration for ambulation postoperatively was 2.0 days in both groups (p = 0.296). Postoperative complications ≥ Grade III Clavien-Dindo classification did not differ significantly between the groups. ConclusionAlthough this study protocol was not feasible because 40% of the patients in the fentanyl group dropped out owing to severe drowsiness, our results show that acetaminophen significantly improved vigilance in the early postoperative period, and its analgesic effect was not significantly different from that of fentanyl.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Acetaminophen-induced hypotension in sepsis

BackgroundAcetaminophen-induced hypotension has been reported in critically ill patients; however, it remains unclear whether mannitol, present as a stabilizing compound in acetaminophen formulations, affects hemodynamic changes. The objectives of this study were to clarify the direct effect of acetaminophen on blood pressure by comparing blood pressure changes after acetaminophen and intravenous immunoglobulin (IVIG) administration, both containing mannitol, in patients with sepsis and understand the risk factors for reduced blood pressure following acetaminophen administration.MethodsThis was a retrospective cohort study. Adult patients who were diagnosed with sepsis at Nippon Medical School Hospital, and who were undergoing continuous arterial blood pressure measurement and received intravenous acetaminophen or IVIG, were included.ResultsOverall, 185 patients were included, with 92 patients in the IVIG group and 93 in the acetaminophen group. The incidence of hypotension was 36.9% in the IVIG group (34 of 92 patients) and 58.0% in the acetaminophen group (54 of 93 patients) (OR = 8.26, p = 0.004). In a propensity score-matched cohort, 80 matched patients were selected. The incidence of hypotension was 37.5% in the IVIG group (15 of 40 patients) and 67.5% in the acetaminophen group (27 of 40 patients) (OR = 7.21, p = 0.007).ConclusionsAcetaminophen induced substantially greater hypotension than IVIG in patients with sepsis, with both containing mannitol. Further studies are needed to clarify the effects on hemodynamics of mannitol contained in acetaminophen formulations.

Twelve-Month Cognitive and Functional Outcomes Following Cardiac Surgery: The DEXACET Trial of Intravenous Acetaminophen Versus Placebo.

Background: Delirium, an acute decline in attention and global cognitive dysfunction, occurs frequently following cardiac surgery and has been demonstrated to be significantly associated with cognitive dysfunction and reduced functional ability. In the DEXACET trial, we demonstrated a significant reduction in postoperative in-hospital delirium with intravenous (IV) acetaminophen when compared with placebo. In this analysis we examined whether this protective association also extended to 12 month cognitive and functional outcomes. Methods: This study was a prospective, randomized, placebo-controlled, triple-blinded, factorial design trial conducted at Beth Israel Deaconess Medical Center, approved by the IRB. In this trial, 120 older cardiac surgical patients were randomly assigned to receive either intravenous (IV) acetaminophen or placebo in addition to propofol or dexmedetomidine. Those receiving IV acetaminophen displayed a significant reduction in in-hospital delirium. We collected cognitive, mood and functional outcome data using the Montreal Cognitive Assessment, telephone version (T-MoCA), Geriatric Depression Scale (GDS) and the Basic and Instrumental Activities of Daily Living (ADLs, IADLs) at 1 month and 12 months after surgery. Results: Of the 120 enrolled patients in the primary trial, 93 (77.5%) and 83 (69.2%) patients responded to assessments at 1 month and 12 months, respectively. No statistically significant differences in median T-MoCA scores were observed between acetaminophen and placebo groups at 1 month (18.0 vs.18.0, p = 0.52) or 12 months (19.0 vs.18.0, p = 0.62) following surgery. There were similarly no differences in GDS, ADLs or IADLs between treatment groups. Losses to follow-up limited the sample sizes and 10 of the 23 (45%) original study participants who had postoperative delirium were lost to follow up. Conclusion: Administration of intravenous acetaminophen was not associated with a difference in long term cognitive or functional status following cardiac surgery. Additional research on long-term outcomes following postoperative delirium with a larger sample size and improved cohort retention strategies will be needed to address this important area.

Comparing the Efficacy and Side Effects of Intravenous Ibuprofen and Acetaminophen in Pain Control Following Laparoscopic Cholecystectomy

BACKGROUNDThe importance of using effective postoperative analgesia is widely accepted. Systemic opioids are the gold standard for reducing severe pain after surgery, but the side effects have limited the use of adequate doses. We aimed to evaluate the effect of adding intravenous acetaminophen and intravenous ibuprofen to fentanyl on patient-controlled analgesia. METHODSIn this randomized clinical trial study in Ardabil city hospital at 2019, 90 patients undergoing elective laparoscopic cholecystectomy were randomly divided into three groups. The control group (n=30) received normal saline, the acetaminophen group (n=30) received 1g intravenous acetaminophen, and the ibuprofen group (n=30) received 800 mg intravenous ibuprofen. All patients received a pain control by intravenous pump containing fentanyl (15µ/ml). The drugs were injected intravenously after surgery. Shoulder and abdominal pain scores, sedation rate, nausea and vomiting, satisfaction, and the doses of fentanyl and meperidine were recorded in SPSS software within 24 h after surgery. RESULTSThe mean abdominal pain scores in ibuprofen (3.02) and acetaminophen (2.89) groups were not significantly different (P=0.719) but were significantly lower than in the control group (5.10) (P<0.001). The severity of shoulder pain, nausea and vomiting, sedation, and fentanyl intake were not significantly different in the ibuprofen and acetaminophen groups but were significantly lower than in the control group.CONCLUSIONThe use of both intravenous acetaminophen and ibuprofen in pain control after surgery can reduce the need for opioid use. Acetaminophen can also be a suitable alternative for postoperative pain control in patients that are unable to use NSAIDs.

The protective effect of carvacrol on acetaminophen-induced renal damage in male rats.

Acetaminophen overdose causes renal injury via oxidative stress and apoptosis induction. Carvacrol has several pharmacological properties such as antioxidant, anti-inflammation and anti-apoptotic effect. The aim of this study was to determine the protective effect of carvacrol on acetaminophen-induced renal damage in rats. Forty male Wistar rats were randomly divided to five groups (n = 8) including control, carvacrol 10mg/kg, acetaminophen, acetaminophen + carvacrol 5mg/kg, and acetaminophen + carvacrol 10mg/kg. Animals received a single dose of acetaminophen (500mg/kg), then were treated with carvacrol for 1 week (daily). Afterwards, renal blood flow (RBF), mean arterial pressure, renal perfusion pressure, renal vascular resistance (RVR), blood urea nitrogen (BUN), and serum creatinine were measured. Also, malondialdehyde (MDA) concentration, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity levels were measured in the kidney tissue. Hematoxylin and eosin method was used for histological assessment. The Western blotting analysis was used to determine the Bax, Bcl-2 and cleaved caspase-3 proteins expression level in the kidney tissue. Carvacrol (10mg/kg) significantly increased the RBF, GPx and SOD activities and also reduced the RVR, serum creatinine, BUN, and MDA in the acetaminophen + carvacrol 10mg/kg group versus acetaminophen group (P < 0.05). Also, carvacrol significantly decreased the cleaved caspase-3, Bax proteins expression level, and kidney tissue damage score in the acetaminophen + carvacrol 10mg/kg group versus acetaminophen group (P < 0.05). This study showed that carvacrol can attenuate the acetaminophen induced acute kidney damage via suppressing oxidative stress and apoptosis biochemical factors.

Macrophage migration inhibitory factor as a potential biomarker in acetaminophen overdose: a pilot study

Acetaminophen overdose is a leading cause of liver failure in the United States. Macrophage migration inhibitory factor (MIF) is a cytokine that is released early and promotes acetaminophen toxicity in preclinical models. This cytokine could prove a useful biomarker in emergency department (ED) patients immediately following an acute acetaminophen overdose. We selected a convenience sample of thirteen patients from a prospective consecutive cohort of ED patients with suspected acute overdose. Research associates collected waste specimens for MIF analysis that remained after use for clinical care. Our team compared patients with confirmed acetaminophen overdose (n = 9) to patients without acetaminophen exposure or liver injury (n = 3) and a patient with liver injury in the absence of detectable acetaminophen (n = 1). In our acetaminophen group, all nine patients had measurable acetaminophen concentrations. Median MIF serum concentrations were 16.08 ng/mL (In this pilot study, MIF was feasible to measure in specimens from an ED drug overdose cohort, and was significantly elevated in the acetaminophen group compared to non-acetaminophen controls without liver injury.

Assessment of the cellular integrity and expression of melatonin receptor (MTNR1A) in the retina assaulted by ethanol and acetaminophen.

Ethanol exposures have been reported to disrupt the development of the retina and optic nerve which can be considered as part of underlying mechanisms of visual pathway impairments. This study aims to investigate the cellular integrity of the retina and the expression of melatonin receptor (MTNR1A) in the retina when assaulted chronically and simultaneously by ethanol and acetaminophen. Animals were randomly grouped into five groups. Control (normal saline), Alcohol group (25% alcohol in 2% sucrose solution), Acetaminophen group, (100mg/kg BW for 14days), Acetaminophen + Alcohol group (25% alcohol in 2% sucrose solution + 100mg/kg BW of paracetamol). Withdrawal group (25% alcohol in 2% sucrose solution + 100mg/kg BW of paracetamol). The body weight and rectal temperature of the animals were taking every 2days and a post mortem study was conducted by quantitatively assessing the markers of oxidative stress. Melatonin level was quantified in the retina tissue and Immunohistochemistry was done via MTNR1A to study the expression of melatonin receptor type 1A in the retina. These results demonstrate that alcohol and acetaminophen significantly reduced the activity of retina rat melatonin (MTNR1A) levels, lowers the SOD and MDA activity. Expression of MTNR1A was reduced in the ganglionic cell layer of Alcohol and acetaminophen group as compared to the control and withdrawal group. It can be inferred that chronic simultaneous intake/consumption of alcohol and acetaminophen altered the melatonin level in the retina and this may implicate the circadian clock and melatonin in Wistar rat visual system.