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Journal of Food and Drug Analysis Apr 2018Acetaminophen (paracetamol or APAP) is an analgesic and antipyretic drug that can induce oxidative stress-mediated hepatotoxicity at high doses. Several studies reported... (Review)
Review
Acetaminophen (paracetamol or APAP) is an analgesic and antipyretic drug that can induce oxidative stress-mediated hepatotoxicity at high doses. Several studies reported that antioxidant nutraceuticals, in particular phenolic phytochemicals from dietary food, spices, herbs and algae have hepatoprotective effects. Others, however, suggested that they may negatively impact the metabolism, efficacy and toxicity of APAP. The aim of this review is to discuss the pros and cons of the association of antioxidant nutraceuticals and APAP by reviewing the in vivo evidence, with particular reference to APAP pharmacokinetics and hepatotoxicity. Results from the murine models of APAP-induced hepatotoxicity showed amelioration of liver damage with nutraceuticals coadministration, as well as reductions in tissue markers of oxidative stress, and serum levels of hepatic enzymes, bilirubin, cholesterol, triglycerides and inflammatory cytokines. On the other hand, both increased and decreased APAP plasma levels have been reported, depending on the nutraceutical type and route of administration. For example, studies showed that repeated administration of flavonoids causes down-regulation of cytochrome P450 enzymes and up-regulation of uridine diphosphate glucuronosyltransferases (UGT). Moreover, nutraceuticals can alter the levels of APAP metabolites, such as mercapturate glucuronide, sulfate and cysteine conjugates. Overall, the reviewed in vivo studies indicate that interactions between APAP and nutraceuticals or plant foods exist. However, the majority of data come from animal models with doses of phytochemicals far from dietary ones. Human studies should investigate gene-diet interactions, as well as ethnic variability in order to clarify the pros and cons of co-administering antioxidant nutraceuticals and APAP.
Topics: Acetaminophen; Animals; Antioxidants; Dietary Supplements; Herb-Drug Interactions; Humans; Oxidative Stress
PubMed: 29703389
DOI: 10.1016/j.jfda.2017.11.004 -
Canadian Family Physician Medecin de... Mar 2017A child with a history of asthma came to my clinic with acute fever. I have heard that acetaminophen might be associated with exacerbation of asthma. Is it safe if I... (Review)
Review
A child with a history of asthma came to my clinic with acute fever. I have heard that acetaminophen might be associated with exacerbation of asthma. Is it safe if I recommend acetaminophen for this child? Most studies suggest an association between acetaminophen use in children and development of asthma later in childhood. However, several confounding factors in study design might contribute to this positive correlation, and without a prospective controlled trial, confirming this finding is challenging. If children have a known history of asthma, it is likely safe to administer a single dose of acetaminophen without concern of precipitating adverse respiratory symptoms. Regular use of acetaminophen to relieve fever or pain does not seem to exacerbate asthma in children more than ibuprofen does.
Topics: Acetaminophen; Age Factors; Antipyretics; Asthma; Child; Child, Preschool; Disease Progression; Dose-Response Relationship, Drug; Humans; Infant; Risk Factors
PubMed: 28292797
DOI: No ID Found -
Gene Expression Jun 2021Genomic and transcriptomic analyses have well established that the major fraction of the mammalian genome is transcribed into different classes of RNAs ranging in size... (Review)
Review
Genomic and transcriptomic analyses have well established that the major fraction of the mammalian genome is transcribed into different classes of RNAs ranging in size from a few nucleotides to hundreds of thousands of nucleotides, which do not encode any protein. Some of these noncoding RNAs (ncRNAs) are directly or indirectly linked to the regulation of expression or functions of 25,000 proteins coded by <2% of the human genome. Among these regulatory RNAs, microRNAs are small (2125 nucleotides) RNAs that are processed from precursor RNAs that have stemloop structure, whereas noncoding RNAs >200 nucleotides are termed long noncoding RNAs (lncRNAs). Circular RNAs (circRNAs) are newly identified lncRNA members that are generated by back-splicing of primary transcripts. The functions of ncRNAs in modulating liver toxicity of xenobiotics are emerging only recently. Acetaminophen (-acetyl--aminophenol, paracetamol or APAP) is a safe analgesic and antipyretic drug at the therapeutic dose. However, it can cause severe liver toxicity that may lead to liver failure if overdosed or combined with alcohol, herbs, or other xenobiotics. This review discusses the role of ncRNAs in acetaminophen metabolism, toxicity, and liver regeneration after APAP-induced liver injury (AILI).
Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Chemical and Drug Induced Liver Injury; Cytochrome P450 Family 3; Humans; RNA, Untranslated
PubMed: 33757622
DOI: 10.3727/105221621X16165282414118 -
Pharmacology Research & Perspectives Aug 2021The precise mechanistic action of acetaminophen (ACT; paracetamol) remains debated. ACT's analgesic and antipyretic actions are attributed to cyclooxygenase (COX)... (Review)
Review
The precise mechanistic action of acetaminophen (ACT; paracetamol) remains debated. ACT's analgesic and antipyretic actions are attributed to cyclooxygenase (COX) inhibition preventing prostaglandin (PG) synthesis. Two COX isoforms (COX1/2) share 60% sequence structure, yet their functions vary. COX variants have been sequenced among various mammalian species including humans. A COX1 splice variant (often termed COX3) is purported by some as the elusive target of ACT's mechanism of action. Yet a physiologically functional COX3 isoform has not been sequenced in humans, refuting these claims. ACT may selectively inhibit COX2, with evidence of a 4.4-fold greater COX2 inhibition than COX1. However, this is markedly lower than other available selective COX2 inhibitors (up to 433-fold) and tempered by proof of potent COX1 inhibition within intact cells when peroxide tone is low. COX isoform inhibition by ACT may depend on subtle in vivo physiological variations specific to ACT. In vivo ACT efficacy is reliant on intact cells and low peroxide tone while the arachidonic acid concentration state can dictate the COX isoform preferred for PG synthesis. ACT is an effective antipyretic (COX2 preference for PG synthesis) and can reduce afebrile core temperature (likely COX1 preference for PG synthesis). Thus, we suggest with specificity to human in vivo physiology that ACT: (i) does not act on a third COX isoform; (ii) is not selective in its COX inhibition; and (iii) inhibition of COX isoforms are determined by subtle and nuanced physiological variations. Robust research designs are required in humans to objectively confirm these hypotheses.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Cyclooxygenase Inhibitors; Humans; Prostaglandin-Endoperoxide Synthases
PubMed: 34278737
DOI: 10.1002/prp2.835 -
NPJ Primary Care Respiratory Medicine Sep 2022Early in the COVID-19 pandemic, anecdotal reports emerged suggesting non-steroidal anti-inflammatory drugs (NSAIDs) may increase susceptibility to infection and... (Review)
Review
Early in the COVID-19 pandemic, anecdotal reports emerged suggesting non-steroidal anti-inflammatory drugs (NSAIDs) may increase susceptibility to infection and adversely impact clinical outcomes. This narrative literature review (March 2020-July 2021) attempted to clarify the relationship between NSAID use and COVID-19 outcomes related to disease susceptibility or severity. Twenty-four relevant publications (covering 25 studies) reporting original research data were identified; all were observational cohort studies, and eight were described as retrospective. Overall, these studies are consistent in showing that NSAIDs neither increase the likelihood of SARS-CoV-2 infection nor worsen outcomes in patients with COVID-19. This is reflected in current recommendations from major public health authorities across the world, which support NSAID use for analgesic or antipyretic treatment during COVID-19. Thus, there is no basis on which to restrict or prohibit use of these drugs by consumers or patients to manage their health conditions and symptoms during the pandemic.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antipyretics; COVID-19; Humans; Pandemics; Retrospective Studies; SARS-CoV-2
PubMed: 36127354
DOI: 10.1038/s41533-022-00300-z -
Inflammopharmacology Feb 2017The antipyretic analgesics, paracetamol, and non-steroidal anti-inflammatory agents NSAIDs are one of the most widely used classes of medications in children. The aim of... (Review)
Review
The antipyretic analgesics, paracetamol, and non-steroidal anti-inflammatory agents NSAIDs are one of the most widely used classes of medications in children. The aim of this review is to determine if there are any clinically relevant differences in safety between ibuprofen and paracetamol that may recommend one agent over the other in the management of fever and discomfort in children older than 3 months of age.
Topics: Acetaminophen; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Child; Drug Overdose; Emergency Medical Services; Fever; Humans; Ibuprofen
PubMed: 28063133
DOI: 10.1007/s10787-016-0302-3 -
Clinical Cardiology Jul 2023
Topics: Humans; Antipyretics; Myocarditis
PubMed: 37249254
DOI: 10.1002/clc.24026 -
BioMed Research International 2021Toxicity and untoward effects are very ostensible in most standard drugs including antipyretic agents. Searching for conceivable antipyretic drugs with minimal...
BACKGROUND
Toxicity and untoward effects are very ostensible in most standard drugs including antipyretic agents. Searching for conceivable antipyretic drugs with minimal toxicities and side effects from traditional plants is a growing concern to date. M. (Asteraceae) is one of the most prominent traditional medicinal plants, which is frequently testified for its traditionally claimed uses of treating fever and different infectious and noninfectious disorders by traditional healers in Ethiopian folk medicine. However, this plant has not been scientifically assessed for its traditionally claimed uses. This study therefore is aimed at investigating the antipyretic and antioxidant activities of 80% methanol root extract and the derived solvent fraction of M. in mouse models.
METHODS
Successive solvent maceration with increased polarity was used as the method of extractions, and chloroform, ethyl acetate, methanol, and water were used as solvents. After extraction, the crude extract and its derived solvent fractions were assessed for their antipyretic activities using yeast-induced pyrexia while, the antioxidant activities were measured in vitro using the diphenyl-2-picrylhydrazyl (DPPH) assay method. Both the extract and solvent fractions were evaluated at the doses of 100, 200, and 400 mg/kg for its antipyretic activities, and the antioxidant activity was evaluated at the doses of 50, 100, 200, 400, 600, 800, and 1000 mg/kg. The positive control group was treated with standard drug (ASA 100 mg/kg), while normal saline-receiving groups were assigned as negative control.
RESULT
. crude extract along with its derived solvent fractions showed statistically significant ( < 0.05, 0.01, and 0.001) temperature reduction activities. The maximum percentage of temperature reduction was observed by the highest dose (400 mg/kg) of the crude extract. The aqueous fraction also showed significantly ( < 0.05 and 0.01) higher temperature reduction than those of ethyl acetate and chloroform fractions. The free radical scavenging activities of the crude extract were also significantly high at the maximum dose, and the aqueous fraction showed the significantly highest antioxidant activity.
CONCLUSION
In general, the data obtained from the present study clarified that the extract possessed significant antipyretic and antioxidant activities, upholding the traditionally claimed use of the plant.
Topics: Animals; Antioxidants; Antipyretics; Drug Evaluation, Preclinical; Echinops Plant; Female; Male; Methanol; Mice; Plant Extracts; Plant Roots
PubMed: 33816625
DOI: 10.1155/2021/6670984 -
Journal of Ethnopharmacology Mar 2023Medicinal plants belonging to the genus Mimosa, such as Mimosa tenuiflora, M. caesalpinifolia, and M. verrucosa are known for their popular use for asthma, bronchitis...
ETHNOPHARMACOLOGICAL RELEVANCE
Medicinal plants belonging to the genus Mimosa, such as Mimosa tenuiflora, M. caesalpinifolia, and M. verrucosa are known for their popular use for asthma, bronchitis and fever. Ethnopharmacological studies report that Mimosa acutistipula is used to treat alopecia and pharyngitis, conditions that can be related to oxidative stress, inflammatory processes and painful limitations. However, there is no studies on its efficacy and mechanism of action.
AIM OF THE STUDY
To elucidate the antioxidant, anti-inflammatory, analgesic and antipyretic activity of M. acutistipula leaves.
MATERIALS AND METHODS
Phytochemical profile of M. acutistipula extracts was evaluated by several reaction-specific methods. Secondary metabolites such as tannins, phenols and flavonoids were quantified with colorimetric assays. In vitro antioxidant potential was evaluated using DPPH and ABTS + as free radical scavenging tests, FRAP and phosphomolybdenum as oxide-reduction assays, and anti-hemolytic for lipid peroxidation evaluation. In vivo anti-inflammatory evaluation was performed by paw edema, and peritonitis induced by carrageenan. Analgesic effect and its possible mechanisms were determined by acetic acid-induced abdominal writhing and the formalin test. Antipyretic activity was evaluated by yeast-induced fever.
RESULTS
Cyclohexane, chloroform, ethyl acetate and methanol extracts of leaves had presence of tannins, flavonoids, phenol, alkaloids, terpenes (except methanolic extract), and saponins (only for methanolic and chloroformic extracts). In phenols, flavonoids and tannins quantification, methanolic and ethyl acetate extract had higher amounts of this phytocompounds. Ethyl acetate extract, due to its more expressive quantity of phenols and flavonoids, was chosen for carrying out the in vivo tests. Due to the relationship between oxidative stress and inflammation, antioxidant tests were performed, showing that ethyl acetate extract had a high total antioxidant activity (70.18%), moderate activity in DPPH radical scavenging, and a moderate ABTS + radical inhibition (33.61%), and FRAP assay (112.32 μg Fe/g). M. acutistipula showed anti-inflammatory activity, with 54.43% of reduction in paw edema (50 mg/kg) when compared to the vehicle. In peritonitis test, a reduction in the concentration of NO could be seen, which is highly involved in the anti-inflammatory activity and is responsible for the increase in permeability. In the analgesic evaluation, most significant results in writhing test were seen at 100 mg/kg, with a 34.7% reduction of writhing. A dual mechanism of action was confirmed with the formalin test, both neurogenic and inflammatory pain were reduced, with a mechanism via opioid route. In the antipyretic test, results were significantly decreased at all concentrations tested.
CONCLUSION
M. acutistipula leaves ethyl acetate extract showed expressive concentrations of phenolic compounds and antioxidant activity. It also exhibited anti-inflammatory and analgesic activity, besides its antipyretic effect. Thus, these results provide information regarding its popular use and might help future therapeutics involving this specimen.
Topics: Antioxidants; Antipyretics; Mimosa; Plant Extracts; Analgesics; Anti-Inflammatory Agents; Pain; Tannins; Flavonoids; Methanol; Phenols; Peritonitis; Edema
PubMed: 36436717
DOI: 10.1016/j.jep.2022.115964 -
Biomedicine & Pharmacotherapy =... Mar 2019Both young and old leaves of Vernonia amygdalina (VA) are traditionally used to treat inflammation, pain and fever. However, the efficacy of young and old leaves for...
BACKGROUND
Both young and old leaves of Vernonia amygdalina (VA) are traditionally used to treat inflammation, pain and fever. However, the efficacy of young and old leaves for treating these ailments have not been compared till date.
AIM
To ascertain the effect of young and old leaves of VA in managing inflammation, pain and fever.
METHODS
Both quantitative and qualitative phytochemical screening of ethanol extracts of young (EthYL) and old (EthOL) leaves of VA were performed. The anti-inflammatory activity of orally administered EthYL and EthOL (50-200 mg/kg) and Diclofenac (10 mg/kg) were evaluated in carrageenan-induced inflammation model in rats. Antipyretic activity of EthYL, EthOL and Aspirin (25 mg/kg) were assessed in the Baker's yeast-induced pyrexia model. Anti-allodynic effect of both extracts were evaluated by inserting inflamed paws of rats in cold water. Antinociceptive property of the extracts were assessed using tail withdrawal and formalin-induced nociception test. Histopathological examination of the paws was performed, in addition to formalin test to understand the possible mechanism of action of the extracts. Negative control rats received 2 ml/kg normal saline in all tests.
RESULTS
The amount of flavonoids, alkaloids, tannins, and phenolics were significantly (p < 0.05) higher in EthOL than EthYL, while saponins were significantly higher (p < 0.05) in EthYL than EthOL. The antioxidant ability and total antioxidant capacity were significantly (p < 0.05) higher in EthYL than EthOL. However, this was significantly (p < 0.05) lower than the anti-oxidant activity of Ascorbic acid. A dose-dependent increase in anti-inflammatory, antipyretic and antinociceptive properties were observed in both EthYL and EthOL, similar to the standard drugs. Mast cell degranulation accompanied by vasodilatation and high leukocytosis were observed in the negative control, but were markedly low in extract treated groups. Both extracts mediated their analgesic effect through opioidergic and nitric oxide pathways with EthYL additionally implicating the muscarinic cholinergic system.
CONCLUSION
Although both EthYL and EthOL alleviate inflammation, pyrexia and nociception, EthYL of VA was found to be more potent than EthOL.
Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Antipyretics; Carrageenan; Edema; Female; Fever; Inflammation; Male; Mice; Mice, Inbred ICR; Nociception; Pain; Phytotherapy; Plant Extracts; Plant Leaves; Rats; Rats, Sprague-Dawley; Vernonia
PubMed: 30841432
DOI: 10.1016/j.biopha.2018.12.147