Sousa Fernanda Severo Sabedra, Baldinotti Rodolfo, Fronza Mariana G, Balaguez Renata, Alves Diego, Brüning César Augusto, Savegnago Lucielli
Programa de Pós-Graduação em Bioquímica e Bioprospecção (PPGBBio), Grupo de Pesquisa em Neurobiotecnologia - GPN, Universidade Federal de Pelotas, UFPel, Postal Code 96010-900, Pelotas, RS, Brazil.
Programa de Pós-Graduação em Biotecnologia (PPGB), Grupo de Pesquisa em Neurobiotecnologia- GPN, Biotecnologia/Centro de Desenvolvimento Tecnológico, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
Brain Res. 2025 Mar 15;1851:149473. doi: 10.1016/j.brainres.2025.149473. Epub 2025 Jan 28.
Chronic pain and depression exhibit a high comorbidity, are challenging to manage, and their pathophysiology mechanisms are intricated and closely related to the up-regulation of pro-inflammatory response and oxidative stress. Chronic pain and depression often coexist and present significant management challenges. Their underlying pathophysiological mechanisms are complex and closely linked to the up-regulation of pro-inflammatory responses and oxidative stress. α-(Phenylselanyl) acetophenone (PSAP), an organoselenium compound, has shown antioxidant, antidepressant-like and antinociceptive effects in animal models. This study aimed to evaluate the effects of acute PSAP administration in a comorbid pain-depression model induced by intracerebroventricular (i.c.v.) injection of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) in male Swiss mice. TNF-α (0.1 ƒg/5 µL, i.c.v.) was injected 1 h before the behavioral tests, followed by acute PSAP treatment (10 mg/kg, intragastrically [i.g.]) 30 min post-TNF-α injection. TNF-α decreased the latency time to first immobility episode and increased the total immobility time of mice in the forced swimming test (FST), effects prevented by PSAP treatment. PSAP also reversed TNF-α-induced nociceptive responses in mice, assessed by the hot plate test. These behavioral improvements may be attributed, at least in part, to the capacity of PSAP treatment reverse the TNF-α-induced increase on reactive species and lipoperoxidation levels, as well as modulate altered activities of antioxidant enzymes catalase and superoxide dismutase in the cerebral cortex and hippocampus. Furthermore, PSAP decreased circulating corticosterone levels elevated by TNF-α injection. In conclusion, PSAP emerges as a promising candidate for the development of innovative therapeutic strategies to address the comorbidity of pain and depression.
慢性疼痛与抑郁症共病率高，治疗颇具挑战，其病理生理机制错综复杂，且与促炎反应和氧化应激的上调密切相关。慢性疼痛和抑郁症常并存，带来重大治疗挑战。它们潜在的病理生理机制复杂，与促炎反应和氧化应激的上调紧密相连。α-（苯硒基）苯乙酮（PSAP）是一种有机硒化合物，已在动物模型中显示出抗氧化、抗抑郁样和抗伤害感受作用。本研究旨在评估急性给予PSAP对雄性瑞士小鼠经脑室内（i.c.v.）注射促炎细胞因子肿瘤坏死因子-α（TNF-α）诱导的疼痛-抑郁共病模型的影响。在行为测试前1小时注射TNF-α（0.1μg/5μL，i.c.v.），随后在TNF-α注射后30分钟进行急性PSAP治疗（10mg/kg，灌胃[i.g.]）。在强迫游泳试验（FST）中，TNF-α缩短了首次不动期的潜伏期并增加了小鼠的总不动时间，而PSAP治疗可预防这些作用。通过热板试验评估，PSAP还逆转了TNF-α诱导的小鼠伤害性反应。这些行为改善可能至少部分归因于PSAP治疗能够逆转TNF-α诱导的活性物质和脂质过氧化水平的升高，以及调节大脑皮层和海马中抗氧化酶过氧化氢酶和超氧化物歧化酶的活性改变。此外，PSAP降低了因注射TNF-α而升高的循环皮质酮水平。总之，PSAP有望成为开发创新治疗策略以解决疼痛和抑郁症共病问题的候选药物。
