Morin mitigates acetaminophen-induced liver injury by potentiating Nrf2 regulated survival mechanism through molecular intervention in PHLPP2-Akt-Gsk3β axis

Abstract Acetaminophen (APAP) is frequently taken to relieve pain. Staggered APAP overdoses have been reported to cause acetaminophen-induced liver injury (AILI). Identification of efficacious therapeutic modalities to address complications imposed by accidental/intentional long-term APAP ingestion is needed. Morin, a plant-derived phytochemical, possesses a multitude of pharmacological properties including hepatoprotective action; however, the underlying mechanisms have been inadequately explored. Our present report demonstrates significant attenuation of APAP-mediated liver injury by morin supplementation in vivo as indicated by reduction in histological and serum markers of hepatotoxicity. Morin not only limited necroinflammation as revealed by reduced HMGB1 release, NALP3 and caspase-1 maturation, but also suppressed oxidative stress and mitochondrial dysfunction. This suggests that morin may have exerted its cytoprotective role by way of early intervention in the pathway leading to perpetuation of AILI. Morin reinforced cellular defenses by suppressing Nrf2 ubiquitination and promoting nuclear Nrf2 retention as well as ARE-Nrf2 binding affinity. The effects were observed to be a result of molecular intervention in the activity of PHLPP2, a phosphatase previously reported by us to subdue cellular Nrf2 responses via Fyn kinase activation. Morin was observed to inhibit APAP-induced increase in PHLPP2 activity ex vivo as well as its association with cellular target ...
Source: Apoptosis - Category: Molecular Biology Source Type: research

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Jeffrey A. SingerPublic health interventions entail non ‐​economic as well as economic trade‐​offs. Some trade ‐​offs can involve other aspects of public health.I havewrittenabout how blanket bans on elective medical procedures combine with the fear already infused in the public to cause crucial delays in necessary health care. This adds to human suffering from causes other than the COVID-19 virus. Many people with chronic conditions, particularlychronic pain patients, are disproportionately affected by reduced access to routine care. Then there ’s the dramatic drop ‐...
Source: Cato-at-liberty - Category: American Health Authors: Source Type: blogs
AbstractPurpose of ReviewThe purpose of this narrative review is to inform readers of the particular impact opioids have had on midlife women and to provide perspective on non-opioid treatment options for women with chronic low back pain.Recent FindingsResearch has shown that midlife women experience more chronic low back pain than men and other age groups of women. As a result, opioids have been particularly deleterious in this demographic group. In addition, there are no data to recommend them for long-term use, while there is a breadth of data on the negative consequences of long-term opioid use. Treatment guidelines no...
Source: Current Obstetrics and Gynecology Reports - Category: OBGYN Source Type: research
Data on all outpatient opioid prescriptions (N = 71,647) to youth below age 21 (N = 42,020) from 2005 to 2016 were extracted from electronic medical records within a university hospital system in New Mexico (NM) as were demographic details and markers of morbidity/mortality. Relative risk was calculated for markers of morbidity/mortality based on sociodemographic characteristics. The sample was primarily male (55.0%), Hispanic/Latinx (50.1%), English-speaking (88.9%), and publicly insured (50.1%). Mean age was 13.54 (SD = 6.50). From 2005 to 2016, overall frequency of opioid prescriptions increased by 86.6% (from 2470 to 4...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
We report a case morphine toxicity in an elderly patient of lung cancer with concomitant presence of chronic obstructive pulmonary disease (COPD) and recent onset renal impairment. Opioid analgesic overdose is a lethal but at the same time, a preventable and treatable condition. We managed the case using naloxone infusion. However, we emphasize early anticipation and recognition of predisposing factors followed by timely intervention to manage this life-threatening condition. PMID: 32421843 [PubMed - in process]
Source: Journal of Opioid Management - Category: Addiction Tags: J Opioid Manag Source Type: research
We describe the historical use of opioids and the scope of the current opioid crisis, review the differences between dependence and addiction, and the private and public sectors response to pain management and highlight the issue of adolescent vulnerability. We conclude with a proposal for future directions that address both public and patient health needs.
Source: Current Opinion in Anaesthesiology - Category: Anesthesiology Tags: PEDIATRIC ANESTHESIA: Edited by Jorge A. Gálvez Source Type: research
Conclusions A 6-month opioid educational intervention did not reduce opioid adverse events or alter opioid use in hospitalized patients. The authors ’ findings suggest that despite opioid and multimodal analgesia awareness, limited-duration educational interventions do not substantially change the hospital use of opioid analgesics.Editor ’s PerspectiveWhat We Already Know about This TopicEducation may promote safer opioid use in hospitalsWhat This Article Tells Us That Is NewThe investigators conducted a difference-in-differences analysis before and after implementation of opioid training in 31 intervention hos...
Source: Anesthesiology - Category: Anesthesiology Source Type: research
The diagnosis of opioid use disorder (OUD) is often overlooked or inadequately managed during the inpatient admission. When recognized, a common strategy is opioid detoxification, an approach that is often ineffective and can be potentially dangerous because of loss of tolerance and subsequent risk for overdose. Medication for addiction treatment (MAT), including methadone and buprenorphine, is effective and can be dispensed in the hospital for both opioid withdrawal and initiation of maintenance treatment. Hospitalists should be knowledgeable about diagnosing and managing patients with OUD, including how to manage acute p...
Source: Medical Clinics of North America - Category: Primary Care Authors: Source Type: research
Cancer survivors have a lower risk for a fatal opioid overdose -- from prescription pain medications or illegal drugs -- than those without the disease, an analysis published Thursday by JAMA Oncology shows.
Source: Health News - UPI.com - Category: Consumer Health News Source Type: news
Conclusion: TBI status, especially in the context of comorbid conditions, should be considered in clinical decisions regarding long-term use of opioids in patients with chronic pain.
Source: The Journal of Head Trauma Rehabilitation - Category: Neurology Tags: Original Articles Source Type: research
CONCLUSIONS: The majority of family medicine clerkships teach about chronic pain, and the amount of time dedicated to this topic has increased over the last 5 years. A state's opioid overdose rate correlates with the amount of time spent teaching about opioids, but does not correlate with the amount of time teaching about other chronic pain subtopics. It is possible that the opioid crisis is causing a shift in the subtopics of chronic pain teaching. PMID: 32401329 [PubMed - as supplied by publisher]
Source: Famly Medicine - Category: Primary Care Authors: Tags: Fam Med Source Type: research
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