Dapagliflozin pretreatment dose-dependently mitigated cisplatin-induced hepatic injury by restoring PI3K/Akt signaling, enhancing antioxidant defenses, and suppressing inflammation.
Does dapagliflozin prevent cisplatin-induced hepatotoxicity in male Wistar albino rats?
Dapagliflozin exerts significant hepatoprotective effects against cisplatin-induced toxicity in a rat model via antioxidant, anti-inflammatory, and cytoprotective mechanisms.
Abstract Background While nephrotoxicity remains the most recognized adverse effect of cisplatin, hepatotoxicity is increasingly acknowledged as a significant clinical concern. Objective This study evaluated the hepatoprotective effect of dapagliflozin (DAPA), a selective sodium–glucose cotransporter-2 inhibitor, focusing on its modulation of the PI3K/Akt–Nrf2/HO-1 signaling pathway. Methods Male Wistar albino rats received oral dapagliflozin (5 or 10 mg/kg/day) for 14 days, with a single intraperitoneal injection of cisplatin (7.5 mg/kg) administered on Day 7. Biochemical, molecular, and histopathological assessments were conducted. Results Cisplatin induced marked hepatic injury, evidenced by body weight loss, hepatomegaly, hyperglycemia, impaired liver function, oxidative stress, inflammation, and apoptosis dysregulation. Dapagliflozin pretreatment significantly and dose-dependently mitigated these effects. It reduced lipid peroxidation and nitric oxide levels while enhancing antioxidant defenses, including Nrf2, heme oxygenase-1, and superoxide dismutase. Additionally, dapagliflozin restored PI3K/Akt signaling, suppressed NF-κB-mediated inflammatory responses, and normalized apoptotic balance. Histological findings corroborated biochemical results, showing preservation of hepatic architecture, particularly at the higher dose. Conclusions Dapagliflozin exerts significant hepatoprotective effects against cisplatin-induced toxicity via antioxidant, anti-inflammatory, and cytoprotective mechanisms, supporting its potential as an adjunct to improve cisplatin safety.
El-ezz et al. (Fri,) conducted a other in Acute cisplatin hepatotoxicity. Dapagliflozin vs. Cisplatin alone was evaluated on Hepatic injury (biochemical, molecular, and histopathological assessments). Dapagliflozin pretreatment dose-dependently mitigated cisplatin-induced hepatic injury by restoring PI3K/Akt signaling, enhancing antioxidant defenses, and suppressing inflammation.