da Fonseca Caren Aline Ramson, Paltian Jaini Janke, da Motta Ketlyn Pereira, Martins Carolina Cristóvão, Kazmierczak Jean Carlo, Schumacher Ricardo Frederico, Soares Mauro Pereira, Luchese Cristiane, Wilhelm Ethel Antunes
Center of Chemical, Pharmaceutical and Food Sciences, Graduate Program in Biochemistry and Bioprospecting, Federal University of Pelotas, Pelotas City 96010-900, Brazil.
Chemistry Department, Graduate Program in Chemistry, Federal University of Santa Maria, Santa Maria City 97105-900, Brazil.
ACS Omega. 2025 Jun 9;10(24):25990-26005. doi: 10.1021/acsomega.5c02655. eCollection 2025 Jun 24.
The underlying mechanisms of rheumatoid arthritis (RA) remain inconclusive; nevertheless, several factors may contribute to developing and exacerbating the disease's signs and symptoms. It is well established that the structure and function of the organism decline with age; consequently, the aging process has become a significant risk factor for several human diseases. Thus, the current study investigated aging as a risk factor for RA in rats and the potential of 4-(phenylselanyl)-2H-chromen-2-one (4-PSCO) as a new therapeutic strategy. Arthritis was induced by intraplantar injection (i.pl.) of complete Freund's adjuvant (CFA; 0.1 mL) in the left hind paw of young and aged adult male Wistar rats. The 4-PSCO (1 mg kg) was administered via the intragastric route for 10 days. CFA administration in aged rats aggravated pain sensitivity by increasing oxidative damage in the central and peripheral nervous systems. The treatment with 4-PSCO reversed pain sensibility, reduced the inflammatory process, and restored the body weight and spleen index. Additionally, 4-PSCO reduced oxidative stress in the paw and spinal cord. Our findings highlight 4-PSCO as a promising therapeutic alternative to develop a more effective and safer drug to treat RA and underscore age-related differences as an important factor for RA pathogenesis.
类风湿关节炎（RA）的潜在发病机制尚无定论；然而，有几个因素可能导致该疾病的体征和症状的发展和加剧。众所周知，生物体的结构和功能会随着年龄的增长而衰退；因此，衰老过程已成为多种人类疾病的重要危险因素。因此，本研究调查了衰老作为大鼠RA的危险因素以及4-（苯硒基）-2H-色烯-2-酮（4-PSCO）作为一种新的治疗策略的潜力。通过在年轻和老年成年雄性Wistar大鼠的左后爪足底注射（i.pl.）完全弗氏佐剂（CFA；0.1 mL）诱导关节炎。通过胃内途径给予4-PSCO（1 mg/kg），持续10天。在老年大鼠中给予CFA会通过增加中枢和外周神经系统的氧化损伤来加重疼痛敏感性。用4-PSCO治疗可逆转疼痛敏感性，减轻炎症过程，并恢复体重和脾脏指数。此外，4-PSCO可降低爪子和脊髓中的氧化应激。我们的研究结果突出了4-PSCO作为开发更有效、更安全的治疗RA药物的有前景的治疗选择，并强调年龄相关差异是RA发病机制的一个重要因素。
