Antifibrotic effect of Parthenolide on unilateral ureteric obstruction induced‑kidney injury in rats: the role of mTOR/PI3K/Akt and NF-κB Signaling Pathways

Background: Renal fibrosis (RF) represents advanced stage of kidney injury, characterized by tubulointerstitial inflammation that promotes fibrotic tissue accumulation. Transforming growth factor-β1 is key cytokine that play a major role in development renal inflammation and fibrosis. Parthenolide (PT) is a natural compound from feverfew plant, known for its anti-inflammatory effects and its role as NF-κB inhibitor. There is interaction between NF-κB and TGF-β signaling pathways across various cell types. So, this research was designed to assess potential impacts of PT on RF resulting from unilateral ureteric obstruction (UUO).Methods: Thirty-two male Wistar albino rats (180–200 g each) were divided into four equal groups: Sham, RF, and two PT-treated groups (1 mg/kg and 2 mg/kg). Intraperitoneal treatment with PT or vehicle started from the day of surgery and continued for 14 days. On day 14, mRNA expression levels of TGF-β1, NF-κB P65, PI3K, Akt, mTOR, and fibronectin in the obstructed kidney were assessed using real-time PCR. Additionally, kidney function and total urinary protein levels were evaluated, and renal tissues from the obstructed side were collected for histopathological and immunohistochemical examination.Results: UUO significantly increased levels of TGF-β1, NF- κB P65, PI3K, Akt, mTOR, and fibronectin (P < 0.05) in the obstructed kidney. Serum creatinine, blood urea nitrogen (BUN), and total urinary proteins were also significantly increased (P < 0.05). PT (1&2 mg/kg) significantly ameliorated the changes induced by UUO. Conclusion: PT exhibited beneficial effects against renal fibrosis induced by UUO in rats, potentially by suppressing the NF-κB and PI3K/Akt/mTOR signaling pathways.