Nicorandil reduces morphine withdrawal symptoms, potentiates morphine antinociception, and ameliorates liver fibrosis in rats

Bedair, Asser F.; Wahid, Ahmed; El–Mezayen, Nesrine S.; Afify, Elham A.

doi:10.1016/j.lfs.2023.121522

Cited by 7 publications

(6 citation statements)

References 101 publications

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“…Hyp is an amino acid unique to collagen, and many diseases can be accompanied by changes in collagen metabolism, causing altered blood, urine, and tissue Hyp levels. Hyp levels in the liver are an important index reflecting the degree of liver fibrosis, and increased Hyp levels in the liver imply increased liver fibrosis ( Bedair et al, 2023 ; Ye et al, 2023 ). Here, we determined Hyp levels in the liver tissue of the rats and found that the Hyp level was the highest in the NAFLD + CIA group, followed by NAFLD group.…”

Section: Resultsmentioning

confidence: 99%

Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats

et al. 2023

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Rheumatoid arthritis (RA) has a high prevalence in patients with non-alcoholic fatty liver disease (NAFLD); however, the underlying mechanism is unclear. To address this, our study established a rat model with both NAFLD and RA by feeding a high-fat diet (HFD) and administering intradermal injection of Freund’s complete adjuvant (FCA) with bovine type II collagen. Collagen-induced RA (CIA) was confirmed by hind paw swelling and histological examination. The histomorphological characteristics of NAFLD were evaluated by Masson’s trichrome and hematoxylin-eosin staining. The development of NAFLD was further evaluated by measuring serum concentrations of triglyceride (TG), total cholesterol (T-CHO), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipopolysaccharide (LPS). The results showed that HFD feeding exacerbated secondary inflammation in CIA rats, whereas FCA/bovine type II collagen injection increased serum levels of ALT, AST, TG, T-CHO, and LPS and exacerbated hepatic fibrosis in both normal and NAFLD rats. Interestingly, NAFLD + CIA significantly promoted the expression of PTRF, a caveolae structure protein involved in hepatic lipid metabolism and affecting downstream signaling of Toll-like receptor 4 (TLR4) and PI3K/Akt activation. High resolution confocal microscopy revealed increased PTRF and TLR4 co-localization in hepatic small vessels of NAFLD + CIA rats. AAV9-mediated PTRF knockdown inhibited TLR4 signaling and alleviated hepatic fibrosis in NAFLD + CIA rats. Together, these findings indicate that NAFLD combined with CIA causes synovial injury and enhances non-alcoholic fatty liver fibrosis in rats. PTRF could attenuate the symptoms of NAFLD + CIA likely by affecting TLR4/PTRF co-expression and downstream signaling.

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Section: Resultsmentioning

confidence: 99%

Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats

et al. 2023

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“…Bedair investigated the therapeutic effect of the analgesic morphine combined with the association of tennis professionals-sensitive potassium channel opener nicodil in the rat model of hepatic fibrosis pain, revealing that this treatment strategy could significantly enhance pain resistance and have a significant hepatoprotective effect. Nicodil also improved morphine dependence in patients [ 25 ]. Chen et al studied the antialgic effects and adverse reactions of flupirtine, a Kv7 potassium channel opener, combined with antihistamines promethazine and fexofenadine on acute and chronic pain in mice.…”

Section: Definition and Classification Of Pain And The Common Drugs U...mentioning

confidence: 99%

Nanomaterial-Based Drug Delivery Systems for Pain Treatment and Relief: From the Delivery of a Single Drug to Co-Delivery of Multiple Therapeutics

Xu,

Dong,

et al. 2023

Pharmaceutics

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The use of nanomaterials in drug delivery systems for pain treatment is becoming increasingly common. This review aims to summarize how nanomaterial-based drug delivery systems can be used to effectively treat and relieve pain, whether via the delivery of a single drug or a combination of multiple therapeutics. By utilizing nanoformulations, the solubility of analgesics can be increased. Meanwhile, controlled drug release and targeted delivery can be realized. These not only improve the pharmacokinetics and biodistribution of analgesics but also lead to improved pain relief effects with fewer side effects. Additionally, combination therapy is frequently applied to anesthesia and analgesia. The co-encapsulation of multiple therapeutics into a single nanoformulation for drug co-delivery has garnered significant interest. Numerous approaches using nanoformulation-based combination therapy have been developed and evaluated for pain management. These methods offer prolonged analgesic effects and reduced administration frequency by harnessing the synergy and co-action of multiple targets. However, it is important to note that these nanomaterial-based pain treatment methods are still in the exploratory stage and require further research to be effectively translated into clinical practice.

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“…On the one hand, the appropriate administration of morphine can effectively alleviate postoperative pain in patients by modulating the central nervous system's response to pain throughout the body. 1 Conversely, the misuse or excessive use of this medication may lead to severe side effects, including a heightened risk of addiction, 2 psychological distress, 3 respiratory depression, 4 physical dependence, 5 and drug tolerance. 6 In humans, morphine undergoes rapid metabolism, yielding two primary metabolites identified as morphine-3-glucuronide ( M3G ) and morphine-6-glucuronide ( M6G ) 7 through the glucuronidation process catalyzed by UDP-glucuronosyl transferase 2B7 (ref.…”

Section: Introductionmentioning

confidence: 99%

Determination of trace morphine and its metabolites in mouse urine using a TpBD functionalized bivalve magnetic nano-adsorbent

Wang,

Chen,

Qian

et al. 2024

Anal. Methods

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Nicorandil reduces morphine withdrawal symptoms, potentiates morphine antinociception, and ameliorates liver fibrosis in rats

Cited by 7 publications

References 101 publications

Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats

Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats

Nanomaterial-Based Drug Delivery Systems for Pain Treatment and Relief: From the Delivery of a Single Drug to Co-Delivery of Multiple Therapeutics

Determination of trace morphine and its metabolites in mouse urine using a TpBD functionalized bivalve magnetic nano-adsorbent

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