PDF(Pubmed)
Abstract：
UNASSIGNED: Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1\'s effect on morphine tolerance remains unexplored. This study aimed to evaluate the influence of ferrostatin-1 on the advancement of morphine tolerance and understand the underlying mechanisms in male rats.
UNASSIGNED: This experiment involved 36 adult male Wistar albino rats with an average weight ranging from 220 to 260 g. These rats were categorized into six groups: Control, single dose ferrostatin-1, single dose morphine, single dose ferrostatin-1 + morphine, morphine tolerance (twice daily for five days), and ferrostatin-1 + morphine tolerance (twice daily for five days). The antinociceptive action was evaluated using both the hot plate and tail-flick tests. After completing the analgesic tests, tissue samples were gathered from the dorsal root ganglia (DRG) for subsequent analysis. The levels of glutathione, glutathione peroxidase 4 (GPX4), and nuclear factor erythroid 2-related factor 2 (Nrf2), along with the measurements of total oxidant status (TOS) and total antioxidant status (TAS), were assessed in the tissues of the DRG.
UNASSIGNED: After tolerance development, the administration of ferrostatin-1 resulted in a significant decrease in morphine tolerance (P < 0.001). Additionally, ferrostatin-1 treatment led to elevated levels of glutathione, GPX4, Nrf2, and TOS (P < 0.001), while simultaneously causing a decrease in TAS levels (P < 0.001).
UNASSIGNED: The study found that ferrostatin-1 can reduce morphine tolerance by suppressing ferroptosis and reducing oxidative stress in DRG neurons, suggesting it as a potential therapy for preventing morphine tolerance.
UNASSIGNED: This experiment involved 36 adult male Wistar albino rats with an average weight ranging from 220 to 260 g. These rats were categorized into six groups: Control, single dose ferrostatin-1, single dose morphine, single dose ferrostatin-1 + morphine, morphine tolerance (twice daily for five days), and ferrostatin-1 + morphine tolerance (twice daily for five days). The antinociceptive action was evaluated using both the hot plate and tail-flick tests. After completing the analgesic tests, tissue samples were gathered from the dorsal root ganglia (DRG) for subsequent analysis. The levels of glutathione, glutathione peroxidase 4 (GPX4), and nuclear factor erythroid 2-related factor 2 (Nrf2), along with the measurements of total oxidant status (TOS) and total antioxidant status (TAS), were assessed in the tissues of the DRG.
UNASSIGNED: After tolerance development, the administration of ferrostatin-1 resulted in a significant decrease in morphine tolerance (P < 0.001). Additionally, ferrostatin-1 treatment led to elevated levels of glutathione, GPX4, Nrf2, and TOS (P < 0.001), while simultaneously causing a decrease in TAS levels (P < 0.001).
UNASSIGNED: The study found that ferrostatin-1 can reduce morphine tolerance by suppressing ferroptosis and reducing oxidative stress in DRG neurons, suggesting it as a potential therapy for preventing morphine tolerance.
摘要：
■Ferrostatin-1和liproxstatin-1，两种铁凋亡抑制剂，保护细胞。Liproxstatin-1降低吗啡耐受性。然而，铁抑制素-1对吗啡耐受的影响仍未被探索。本研究旨在评估Ferratin-1对雄性大鼠吗啡耐受的影响，并了解其潜在机制。
■该实验涉及36只成年雄性Wistar白化病大鼠，平均体重为220至260g。这些大鼠分为六组：对照组，单剂量铁抑制素-1，单剂量吗啡，单剂量铁抑素-1+吗啡，吗啡耐受性（每天两次，共五天），和铁抑制素-1+吗啡耐受（每天两次，共五天）。使用热板和甩尾试验评估抗伤害感受作用。完成镇痛试验后,从背根神经节(DRG)收集组织样本用于后续分析。谷胱甘肽的水平，谷胱甘肽过氧化物酶4（GPX4），和核因子红系2相关因子2（Nrf2），连同总氧化剂状态(TOS)和总抗氧化剂状态(TAS)的测量，在DRG的组织中进行评估。
■公差发展后，使用铁抑素-1导致吗啡耐受显著降低(P<0.001).此外,铁抑制素-1治疗导致谷胱甘肽水平升高，GPX4、Nrf2和TOS（P<0.001），同时导致TAS水平降低（P<0.001）。
■研究发现，铁抑制素-1可以通过抑制DRG神经元的铁凋亡和减少氧化应激来降低吗啡的耐受性，提示它是预防吗啡耐受的潜在疗法。
■该实验涉及36只成年雄性Wistar白化病大鼠，平均体重为220至260g。这些大鼠分为六组：对照组，单剂量铁抑制素-1，单剂量吗啡，单剂量铁抑素-1+吗啡，吗啡耐受性（每天两次，共五天），和铁抑制素-1+吗啡耐受（每天两次，共五天）。使用热板和甩尾试验评估抗伤害感受作用。完成镇痛试验后,从背根神经节(DRG)收集组织样本用于后续分析。谷胱甘肽的水平，谷胱甘肽过氧化物酶4（GPX4），和核因子红系2相关因子2（Nrf2），连同总氧化剂状态(TOS)和总抗氧化剂状态(TAS)的测量，在DRG的组织中进行评估。
■公差发展后，使用铁抑素-1导致吗啡耐受显著降低(P<0.001).此外,铁抑制素-1治疗导致谷胱甘肽水平升高，GPX4、Nrf2和TOS（P<0.001），同时导致TAS水平降低（P<0.001）。
■研究发现，铁抑制素-1可以通过抑制DRG神经元的铁凋亡和减少氧化应激来降低吗啡的耐受性，提示它是预防吗啡耐受的潜在疗法。
