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European Heart Journal Jul 2023
Topics: Humans; Aspirin; Platelet Aggregation Inhibitors; Perioperative Care
PubMed: 37155334
DOI: 10.1093/eurheartj/ehad246 -
Inflammopharmacology Feb 2024This review will discuss evidence that aspirin possesses anticancer activity. Long-term observational retrospective studies on nurses and health professionals... (Review)
Review
This review will discuss evidence that aspirin possesses anticancer activity. Long-term observational retrospective studies on nurses and health professionals demonstrated that regular aspirin users had a significantly lower incidence of colorectal cancer (RCT). Prospective studies on patients with a high risk of developing colorectal polyps/cancer confirmed that aspirin use significantly lowered colorectal dysplasia. Numerous observational studies focused on the use of aspirin in a broad range of cancers demonstrating a consistent 20-30% preventive effect on cancer incidence and mortality. Random Controlled Trials provided conflicting results on the benefit of aspirin in preventing CRC. Based on the age, weight/body size of the subjects for reasons still being explored. Studies on rats/mice further demonstrated that treatment of animals with aspirin where colon cancer was induced chemically or genetically (APCMin mice) reduced colonic dysplasia and polyp formation. Aspirin treatment was also effective at reducing the growth of cancer cells transplanted into normal/immunocompromised mice, suggesting that aspirin may be effective in treating different cancers. This possibility is also supported in clinical studies that aspirin use pre- and postcancer diagnosis significantly reduced the metastatic spread of cancer and increased patient survival. Lastly, the importance of the antiplatelet actions of aspirin in the drug's anticancer activity and specifically cancer metastatic spread is discussed and the current controversy related to the conflicting recommendations of the USPSTF over the past five years on the use of aspirin to prevent CRC.
Topics: Humans; Mice; Rats; Animals; Aspirin; Anti-Inflammatory Agents, Non-Steroidal; Retrospective Studies; Prospective Studies; Colorectal Neoplasms
PubMed: 38064111
DOI: 10.1007/s10787-023-01346-2 -
International Journal of Molecular... Dec 2023Intestinal inflammation is a complex and recurrent inflammatory disease. Pharmacological and pharmacodynamic experiments showed that aspirin eugenol ester (AEE) has good...
Intestinal inflammation is a complex and recurrent inflammatory disease. Pharmacological and pharmacodynamic experiments showed that aspirin eugenol ester (AEE) has good anti-inflammatory, antipyretic, and analgesic effects. However, the role of AEE in regulating intestinal inflammation has not been explored. This study aimed to investigate whether AEE could have a protective effect on LPS-induced intestinal inflammation and thus help to alleviate the damage to the intestinal barrier. This was assessed with an inflammation model in Caco-2 cells and in rats induced with LPS. The expression of inflammatory mediators, intestinal epithelial barrier-related proteins, and redox-related signals was analyzed using an enzyme-linked immunosorbent assay (ELISA), Western blotting, immunofluorescence staining, and RT-qPCR. Intestinal damage was assessed by histopathological examination. Changes in rat gut microbiota and their functions were detected by the gut microbial metagenome. AEE significantly reduced LPS-induced pro-inflammatory cytokine levels ( < 0.05) and oxidative stress levels in Caco-2 cells and rats. Compared with the LPS group, AEE could increase the relative expression of Occludin, Claudin-1, and zonula occludens-1 (ZO-1) and decrease the relative expression of kappa-B (NF-κB) and matrix metalloproteinase-9. AEE could significantly improve weight loss, diarrhea, reduced intestinal muscle thickness, and intestinal villi damage in rats. Metagenome results showed that AEE could regulate the homeostasis of the gut flora and alter the relative abundance of and . Flora enrichment analysis indicated that the regulation of gut flora with AEE may be related to the regulation of glucose metabolism and energy metabolism. AEE could have positive effects on intestinal inflammation-related diseases.
Topics: Humans; Rats; Animals; Lipopolysaccharides; Caco-2 Cells; Aspirin; Intestinal Mucosa; Inflammation; Eugenol; Intestinal Diseases
PubMed: 38139262
DOI: 10.3390/ijms242417434 -
Journal of Medicinal Food May 2024Jojoba oil, which is extracted from jojoba plant seeds that are native to North America, possesses a unique molecular structure and is distinct from other oils. Unlike...
Jojoba oil, which is extracted from jojoba plant seeds that are native to North America, possesses a unique molecular structure and is distinct from other oils. Unlike typical oils, which mostly contain triglycerides, jojoba oil is composed of long monounsaturated esters, affording it exceptional properties and is valuable across cosmetics, chemicals, and pharmaceuticals. While jojoba oil is prevalent in beauty and skincare today, its seeds and oil have ancient roots in folk medicine, used for treating skin and scalp issues, wounds, sore throats, obesity, and even cancer, while enhancing immunity and fostering hair growth. Modern research underscores jojoba oil's pharmacological versatility, demonstrating antioxidant, antidiabetic, anti-acne, anti-inflammatory, antipyretic, and antibacterial properties. Notably, there has been a surge in its utilization in pharmaceuticals, particularly in topical, transdermal, and parenteral formulations. This review provides a comprehensive overview of jojoba oil, encompassing its chemical composition, extraction techniques, health advantages, and pharmaceutical application developments.
PubMed: 38695844
DOI: 10.1089/jmf.2023.k.0062 -
Advances in Therapy Jul 2024Although aspirin is deeply rooted in the most ancient history of medicine, the mechanism of action of this drug was only identified a few decades ago. Aspirin has... (Review)
Review
Although aspirin is deeply rooted in the most ancient history of medicine, the mechanism of action of this drug was only identified a few decades ago. Aspirin has several indications ranging from its long-known analgesic and antipyretic properties to the more recently discovered antithrombotic, chemopreventive and anti-eclampsia actions. In addition, a recent line of research has identified aspirin as a drug with potential hepatologic indications. This article specifically focuses on the nonalcoholic fatty liver disease/nonalcoholic metabolic dysfunction fatty liver disease/metabolic dysfunction-associated steatotic liver disease (NAFLD/MAFLD/MASLD) field. To this end, the most recently published randomized controlled trial on aspirin for non-cirrhotic MASLD is summarized and discussed. Moreover, previous epidemiologic evidence supporting the notion that aspirin exerts antisteatotic and antifibrotic hepatic effects, which may result in the primary prevention of hepatocellular carcinoma, is also addressed. Next, the putative mechanisms involved are examined, with reference to the effects on adipose tissue and liver and sex differences in the action of aspirin. It is concluded that these novel findings on aspirin as a "hepatologic drug" deserve additional in-depth evaluation.
Topics: Humans; Aspirin; Non-alcoholic Fatty Liver Disease; Female; Randomized Controlled Trials as Topic; Fatty Liver; Male; Liver Neoplasms; Anti-Inflammatory Agents, Non-Steroidal; Carcinoma, Hepatocellular; Liver
PubMed: 38748333
DOI: 10.1007/s12325-024-02885-y -
Pharmacology 2024Acetaminophen (APAP) is commonly used as an antipyretic and analgesic agent. Excessive APAP can induce liver toxicity, known as APAP-induced liver injury (ALI). The... (Review)
Review
BACKGROUND
Acetaminophen (APAP) is commonly used as an antipyretic and analgesic agent. Excessive APAP can induce liver toxicity, known as APAP-induced liver injury (ALI). The metabolism and pathogenesis of APAP have been extensively studied in recent years, and many cellular processes such as autophagy, mitochondrial oxidative stress, mitochondrial dysfunction, and liver regeneration have been identified to be involved in the pathogenesis of ALI. Caveolin-1 (CAV-1) as a scaffold protein has also been shown to be involved in the development of various diseases, especially liver disease and tumorigenesis. The role of CAV-1 in the development of liver disease and the association between them remains a challenging and uncharted territory.
SUMMARY
In this review, we briefly explore the potential therapeutic effects of CAV-1 on ALI through autophagy, oxidative stress, and lipid metabolism. Further research to better understand the mechanisms by which CAV-1 regulates liver injury will not only enhance our understanding of this important cellular process, but also help develop new therapies for human disease by targeting CAV-1 targets.
KEY MESSAGES
This review briefly summarizes the potential protective mechanisms of CAV-1 against liver injury caused by APAP.
Topics: Acetaminophen; Caveolin 1; Humans; Animals; Chemical and Drug Induced Liver Injury; Oxidative Stress; Autophagy; Analgesics, Non-Narcotic; Lipid Metabolism
PubMed: 38657589
DOI: 10.1159/000538017 -
Molecular Metabolism Nov 2023Mitochondrial pyruvate is a critical intermediary metabolite in gluconeogenesis, lipogenesis, and NADH production. As a result, the mitochondrial pyruvate carrier (MPC)...
OBJECTIVE
Mitochondrial pyruvate is a critical intermediary metabolite in gluconeogenesis, lipogenesis, and NADH production. As a result, the mitochondrial pyruvate carrier (MPC) complex has emerged as a promising therapeutic target in metabolic diseases. Clinical trials are currently underway. However, recent in vitro data indicate that MPC inhibition diverts glutamine/glutamate away from glutathione synthesis and toward glutaminolysis to compensate for loss of pyruvate oxidation, possibly sensitizing cells to oxidative insult. Here, we explored this in vivo using the clinically relevant acetaminophen (APAP) overdose model of acute liver injury, which is driven by oxidative stress.
METHODS
We used pharmacological and genetic approaches to inhibit MPC2 and alanine aminotransferase 2 (ALT2), individually and concomitantly, in mice and cell culture models and determined the effects on APAP hepatotoxicity.
RESULTS
We found that MPC inhibition sensitizes the liver to APAP-induced injury in vivo only with concomitant loss of alanine aminotransferase 2 (ALT2). Pharmacological and genetic manipulation of neither MPC2 nor ALT2 alone affected APAP toxicity, but liver-specific double knockout (DKO) significantly worsened APAP-induced liver damage. Further investigation indicated that DKO impaired glutathione synthesis and increased urea cycle flux, consistent with increased glutaminolysis, and these results were reproducible in vitro. Finally, induction of ALT2 and post-treatment with dichloroacetate both reduced APAP-induced liver injury, suggesting new therapeutic avenues.
CONCLUSIONS
Increased susceptibility to APAP toxicity requires loss of both the MPC and ALT2 in vivo, indicating that MPC inhibition alone is insufficient to disrupt redox balance. Furthermore, the results from ALT2 induction and dichloroacetate in the APAP model suggest new metabolic approaches to the treatment of liver damage.
Topics: Mice; Animals; Antioxidants; Acetaminophen; Pyruvic Acid; Alanine Transaminase; Chemical and Drug Induced Liver Injury; Oxidative Stress; Liver Diseases; Oxidation-Reduction; Glutathione; Alanine
PubMed: 37716594
DOI: 10.1016/j.molmet.2023.101808 -
Inflammopharmacology Dec 2023Acetylsalicylic acid (ASA), also known as aspirin, was discovered in 1897 as an acetylated form of salicylate. It has been widely used for its anti-inflammatory and... (Review)
Review
Acetylsalicylic acid (ASA), also known as aspirin, was discovered in 1897 as an acetylated form of salicylate. It has been widely used for its anti-inflammatory and antiplatelet effects. It is commonly used for its cardiovascular benefits and is prescribed as secondary prophylaxis after a heart attack. Furthermore, low-dose, long-term ASA is used to reduce the risk of heart attack and stroke in individuals without prior cardiovascular disease. Acetylsalicylic acid acts as a non-selective inhibitor of cyclooxygenase (COX), which inhibits the synthesis of prostaglandins and prevents pro-inflammatory cytokines. Findings suggest that targeting cytokines and growth factors could be a potential therapeutic strategy for reducing neuroinflammation and slowing down the progression of dementia. Additionally, prostaglandins contribute to synaptic plasticity and can act as retrograde messengers in synapses. Research has implicated COX-1, one of the isoforms of the enzyme, in neuroinflammation and neurodegenerative disorders. The inhibition of COX-1 might potentially prevent impairments in working memory and reduce neuroinflammation caused by beta-amyloid proteins in some conditions, such as Alzheimer's disease (AD). Cyclooxygenase-2, an inducible form of the enzyme, is expressed in cortical and hippocampal neurons and is associated with long-term synaptic plasticity. The inhibition or knockout of COX-2 has been shown to decrease long-term potentiation, a process involved in memory formation. Studies have also demonstrated that the administration of COX-2 inhibitors impairs cognitive function and memory acquisition and recall in animal models. There remains a debate regarding the effects of aspirin on dementia and cognitive decline. Although some studies suggest a possible protective effect of non-steroidal anti-inflammatory drugs, including aspirin, against the development of AD, others have shown inconsistent evidence. This review provides an overview of the effects of ASA or its active metabolite salicylate on learning, memory, and synaptic plasticity.
Topics: Animals; Humans; Aspirin; Neuroinflammatory Diseases; Alzheimer Disease; Memory Disorders; Anti-Inflammatory Agents; Prostaglandins; Cyclooxygenase 2; Myocardial Infarction; Cytokines
PubMed: 37924473
DOI: 10.1007/s10787-023-01347-1 -
The American Journal of Medicine Feb 2024Pain is prevalent in patients with cirrhosis. Due to potential alterations in drug metabolism, risk for adverse effects, and complications from cirrhosis, physicians are... (Review)
Review
Pain is prevalent in patients with cirrhosis. Due to potential alterations in drug metabolism, risk for adverse effects, and complications from cirrhosis, physicians are often faced with difficult choices when choosing appropriate analgesics in these patients. Overall, acetaminophen remains the preferred analgesic. Despite its potential for intrinsic liver toxicity, acetaminophen is safe when used at 2 g/d. In contrast, non-selective nonsteroidals should be avoided due to their multiple side effects, including worsening renal function, blunting diuretic response, and increasing risk of portal hypertensive and peptic ulcer bleeding. Celecoxib can be administered for short term (≤5 days) in patients with Child's A and Child's B cirrhosis (50% dose reduction). Opioids carry the risk of precipitating hepatic encephalopathy and should generally be avoided, when possible. If clinical situation demands their use, opioid use should be limited to short-acting agents for short duration. Gabapentin and pregabalin are generally safe. Duloxetine should be avoided in hepatic impairment. Topical diclofenac and lidocaine seem to be safe in patients with cirrhosis.
Topics: Child; Humans; Acetaminophen; Analgesics; Analgesics, Opioid; Gabapentin; Liver Cirrhosis; Pain
PubMed: 37918778
DOI: 10.1016/j.amjmed.2023.10.022 -
Best Practice & Research. Clinical... Jun 2024Preeclampsia (PE) is a complex heterogeneous disorder with overlapping clinical phenotypes that complicate diagnosis and management. Although several pathophysiological... (Review)
Review
Preeclampsia (PE) is a complex heterogeneous disorder with overlapping clinical phenotypes that complicate diagnosis and management. Although several pathophysiological mechanisms have been proposed, placental dysfunction due to inadequate remodelling of uterine spiral arteries leading to mal-perfusion and syncytiotrophoblast stress is recognized as the unifying characteristic of early-onset PE. Placental overgrowth and or premature senescence are probably the causes of late-onset PE. The frequency of PE has increased over the last few decades due to population-wide increases in risk factors viz. obesity, diabetes, multifetal pregnancies and pregnancies at an advanced maternal age. Whilst multimodal tools with components comprising risk factors, biomarkers and sonography are used for predicting PE, aspirin is most effective in preventing early-onset PE. The incidence and clinical consequences of PE and eclampsia are influenced by socioeconomic and cultural factors, therefore management strategies should involve multi-sector partnerships to mitigate the adverse outcomes.
Topics: Humans; Female; Pre-Eclampsia; Pregnancy; Eclampsia; Developing Countries; Risk Factors; Maternal Mortality; Aspirin
PubMed: 38513504
DOI: 10.1016/j.bpobgyn.2024.102473