The Melatonin Type 2 Receptor Agonist IIK7 Attenuates and Reverses Morphine Tolerance in Neuropathic Pain Rats Through the Suppression of Neuroinflammation in the Spinal Cord DOI Creative Commons
Yaswanth Kuthati, Chih‐Shung Wong

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(12), P. 1638 - 1638

Published: Dec. 5, 2024

Background: Morphine analgesic tolerance (MAT) limits the clinical application of morphine in management chronic pain. IIK7 is a melatonin type 2 (MT2) receptor agonist known to have antioxidant properties. Oxidative stress recognized as critical factor MAT. This study sought assess impact on progression MAT and its potential reverse pre-existing Methods: Wistar rats underwent partial sciatic nerve transection (PSNT) surgery induce neuropathic pain (NP). Seven days post transection, we implanted an intrathecal (i.t.) catheter linked it osmotic pump. Rats were randomly divided into following groups: sham-operated/vehicle, PSNT/vehicle, PSNT/IIK7 50 ng/h, PSNT/MOR 15 g/h, g + ng/h. We two i.t. catheters for drug administration evaluation efficacy reversing pre-established one pump MOR or saline continuous infusion. On 7th day, was disconnected, μg vehicle administered through second catheter. After 3 h, administered, animal behavior tests performed. measured levels mRNA Nrf2 HO-1, pro-inflammatory cytokines (PICs), microglial astrocyte activation spinal cord. Results: The co-administration with delayed development PSNT by restoring HO-1 while also inhibiting microglial-cell activation, alongside suppression PICs. Additionally, single injection high-dose efficient MOR’s antinociception MOR-tolerant rats. Conclusions: Our results indicate that co-infusion ultra-low-dose can delay high dose

Language: Английский

Morphine's role in macrophage polarization: Exploring M1 and M2 dynamics and disease susceptibility DOI
Jonaid Ahmad Malik,

Javed N. Agrewala

Journal of Neuroimmunology, Journal Year: 2025, Volume and Issue: 400, P. 578534 - 578534

Published: Jan. 23, 2025

Language: Английский

Citations

2

Epigoitrin ameliorates acute liver injury in mice via regulation of the TLR4/NF-κB signaling pathway DOI

Mingli Zhuge,

Hongjing Liu, Lang Qin

et al.

Published: May 7, 2025

Abstract Background Acute liver injury (ALI), frequently triggered by drugs, toxins, or viral infections, is closely associated with the aberrant activation of TLR4/NF-κB signaling pathway. Epigoitrin (EPG), a major bioactive component derived from Isatis indigotica root, exhibits anti-inflammatory, antioxidant properties, and potential NF-κB inhibitory effects. However, specific mechanisms underlying its therapeutic action in ALI remain to be elucidated. Objective To investigate protective effects EPG against carbon tetrachloride (CCl4)-induced mice. Methods Kunming mice were randomly divided into five groups: normal control group, model bifendate high-dose low-dose group. The treatment groups received corresponding doses while given an equal volume distilled water via intragastric gavage once daily for 7 consecutive days. One hour after final administration, all except group intraperitoneally injected 0.2% CCl₄-olive oil solution induce injury. Sixteen hours post-injection, blood samples collected measure serum levels aspartate aminotransferase (AST) alanine (ALT). Liver tissues harvested assess interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) using enzyme-linked immunosorbent assay (ELISA). Hematoxylin eosin (H&E) staining was performed observe histopathological changes liver. on Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway evaluated quantitative real-time PCR Western blot analysis. Results EPG significantly reduced function markers (ALT AST) pro-inflammatory cytokines, including (TNF-α), (P<0.05). Histopathological examination demonstrated that effectively ameliorated CCl₄-induced hepatocellular necrosis. Furthermore, qPCR (WB) analyses revealed markedly suppressed Conclusion exerts effect mice, mechanism may involve suppression

Language: Английский

Citations

0

The Melatonin Type 2 Receptor Agonist IIK7 Attenuates and Reverses Morphine Tolerance in Neuropathic Pain Rats Through the Suppression of Neuroinflammation in the Spinal Cord DOI Creative Commons
Yaswanth Kuthati, Chih‐Shung Wong

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(12), P. 1638 - 1638

Published: Dec. 5, 2024

Background: Morphine analgesic tolerance (MAT) limits the clinical application of morphine in management chronic pain. IIK7 is a melatonin type 2 (MT2) receptor agonist known to have antioxidant properties. Oxidative stress recognized as critical factor MAT. This study sought assess impact on progression MAT and its potential reverse pre-existing Methods: Wistar rats underwent partial sciatic nerve transection (PSNT) surgery induce neuropathic pain (NP). Seven days post transection, we implanted an intrathecal (i.t.) catheter linked it osmotic pump. Rats were randomly divided into following groups: sham-operated/vehicle, PSNT/vehicle, PSNT/IIK7 50 ng/h, PSNT/MOR 15 g/h, g + ng/h. We two i.t. catheters for drug administration evaluation efficacy reversing pre-established one pump MOR or saline continuous infusion. On 7th day, was disconnected, μg vehicle administered through second catheter. After 3 h, administered, animal behavior tests performed. measured levels mRNA Nrf2 HO-1, pro-inflammatory cytokines (PICs), microglial astrocyte activation spinal cord. Results: The co-administration with delayed development PSNT by restoring HO-1 while also inhibiting microglial-cell activation, alongside suppression PICs. Additionally, single injection high-dose efficient MOR’s antinociception MOR-tolerant rats. Conclusions: Our results indicate that co-infusion ultra-low-dose can delay high dose

Language: Английский

Citations

1