Scholarlink

Background <p>Ebastine (EBT), a second-generation antihistamine, exhibits notable antioxidant and anti-inflammatory effects. EBT may serve as a promising therapeutic candidate for limiting drug-induced lung injury. This study investigated the protective effects of EBT against cisplatin-associated pulmonary toxicity and explored the underlying mechanisms of this protection. The disturbance of autophagy via the dysregulated PI3K/mTOR/ULK1 pathway was evaluated as well as its influence on pulmonary toxicity.</p> Methods <p>This study examined the effects of EBT (1&#xa0;mg/kg orally) on pulmonary injury induced by cisplatin (7.5&#xa0;mg/kg I.P.) in rats. Pulmonary tissue levels of oxidative stress and inflammatory markers were measured, while histopathological alterations and collagen deposition were examined using hematoxylin and eosin staining and Masson’s trichrome staining, respectively. The molecular mechanisms by which EBT mitigates pulmonary injury were investigated.</p> Results <p>The findings demonstrated that EBT ameliorated pulmonary function by suppressing the observed pathological tissue changes. EBT exhibited antioxidant and anti-inflammatory properties through decreasing levels of several evaluated proinflammatory markers while enhancing levels of anti-inflammatory enzymes and interleukins. Furthermore, EBT treatment was associated with reduced expression of AMPK, TSC1, TSC2, PI3K, PDK1, CD36, and IGF-1, and with increased expression of miRNA-101 and ULK1, as demonstrated by Western blotting and PCR. Additionally, the effect on pulmonary tissue viability was underscored by elevated Bcl-2 levels and reduced caspase-3 staining in immunohistopathological analysis.</p> Conclusions <p>EBT effectively attenuated cisplatin-induced pulmonary injury in rats, and these protective effects were associated with modulation of oxidative stress, inflammatory responses, and alterations in the miR-101/PI3K/mTOR/ULK1 signaling axis. Further mechanistic and clinical investigations are warranted to confirm these molecular interactions and evaluate therapeutic applicability in patients.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Ebastine mitigates cisplatin-induced pulmonary injury associated with alterations in the miR-101/PI3K/mTOR/ULK1 signaling axis

  • 期刊论文

  • 发表日期：

    2026年6月24日

查看全文
  • Nayef A. Aldabaan,
  • Basel A. Abdel-Wahab,
  • Ehab A.M. El-Shoura,
  • Saad Misfer Alqahtani,
  • Ibrahim S. Alalhareth,
  • Mohamed A. Doma,
  • Hebatallah M. Saad,
  • Marwa B. Bakir,
  • Mohamed A. Gad,
  • Dalia Zaafar

摘要

Background

Ebastine (EBT), a second-generation antihistamine, exhibits notable antioxidant and anti-inflammatory effects. EBT may serve as a promising therapeutic candidate for limiting drug-induced lung injury. This study investigated the protective effects of EBT against cisplatin-associated pulmonary toxicity and explored the underlying mechanisms of this protection. The disturbance of autophagy via the dysregulated PI3K/mTOR/ULK1 pathway was evaluated as well as its influence on pulmonary toxicity.

Methods

This study examined the effects of EBT (1 mg/kg orally) on pulmonary injury induced by cisplatin (7.5 mg/kg I.P.) in rats. Pulmonary tissue levels of oxidative stress and inflammatory markers were measured, while histopathological alterations and collagen deposition were examined using hematoxylin and eosin staining and Masson’s trichrome staining, respectively. The molecular mechanisms by which EBT mitigates pulmonary injury were investigated.

Results

The findings demonstrated that EBT ameliorated pulmonary function by suppressing the observed pathological tissue changes. EBT exhibited antioxidant and anti-inflammatory properties through decreasing levels of several evaluated proinflammatory markers while enhancing levels of anti-inflammatory enzymes and interleukins. Furthermore, EBT treatment was associated with reduced expression of AMPK, TSC1, TSC2, PI3K, PDK1, CD36, and IGF-1, and with increased expression of miRNA-101 and ULK1, as demonstrated by Western blotting and PCR. Additionally, the effect on pulmonary tissue viability was underscored by elevated Bcl-2 levels and reduced caspase-3 staining in immunohistopathological analysis.

Conclusions

EBT effectively attenuated cisplatin-induced pulmonary injury in rats, and these protective effects were associated with modulation of oxidative stress, inflammatory responses, and alterations in the miR-101/PI3K/mTOR/ULK1 signaling axis. Further mechanistic and clinical investigations are warranted to confirm these molecular interactions and evaluate therapeutic applicability in patients.

Graphical Abstract