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<p>Cisplatin is widely used in pediatric oncology but is limited by its dose-dependent nephrotoxicity. The renin–angiotensin–aldosterone system (RAAS) has been implicated in cisplatin-induced renal injury. Losartan, an angiotensin II receptor blocker, may offer renal protection; however, its effects on apoptosis and regeneration in this context remain unclear. This study aimed to investigate the potential protective role of losartan against cisplatin-induced nephrotoxicity, specifically by assessing its impact on apoptosis and tubular regeneration. Fifteen female BALB/c mice were randomly assigned to three groups (<i>n</i> = 5 per group): Control, cisplatin (12.7&#xa0;mg/kg, i.p., single dose), and cisplatin + losartan (10&#xa0;mg/kg/day, oral). Losartan was administered for nine consecutive days, starting 4&#xa0;days before cisplatin exposure. Histopathological examination, active caspase-3 immunostaining (for apoptosis), and 5-bromo-2-deoxyuridine (BrdU) labeling (for cell proliferation) were performed. Glomerular and tubular injury scores, caspase-3 H-scores, and BrdU-positive cell counts were statistically analyzed using the Kruskal–Wallis H and Mann–Whitney <i>U</i> tests. Cisplatin significantly increased glomerular (<i>p</i> = 0.006, <i>p</i> = 0.005, <i>p</i> = 0.006) and tubular injury scores (<i>p</i> = 0.008, <i>p</i> = 0.007, <i>p</i> = 0.007, <i>p</i> = 0.007, <i>p</i> = 0.007), elevated active caspase-3 expression (<i>p</i> = 0.002), and reduced BrdU-positive cell counts (<i>p</i> = 0.009) compared to control. Losartan co-treatment significantly reduced glomerular (<i>p</i> = 0.008, <i>p</i> = 0.005, <i>p</i> = 0.008) and tubular injury (<i>p</i> = 0.008, <i>p</i> = 0.008, <i>p</i> = 0.009, <i>p</i> = 0.008, v) and decreased caspase-3 expression (<i>p</i> = 0.009). Additionally, BrdU-positive cell counts were significantly higher in the cisplatin + losartan group compared to both control and cisplatin groups (<i>p</i> = 0.009), indicating enhanced regeneration. Losartan mitigates cisplatin-induced nephrotoxicity by suppressing apoptosis and promoting tubular regeneration. These findings support the potential therapeutic role of RAAS inhibition in preventing cisplatin-associated renal injury.</p>

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Assessment of protective effect of the losartan against cisplatin-induced nephrotoxicity in mice

  • 期刊论文

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  • 发表日期：

    2025年5月3日

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  • Selçuk Teke,
  • Gülsen Bayrak,
  • Erdem Ak,
  • Ali Can Korkmaz,
  • Şakir Necat Yilmaz,
  • Ali Delibaş

摘要

Cisplatin is widely used in pediatric oncology but is limited by its dose-dependent nephrotoxicity. The renin–angiotensin–aldosterone system (RAAS) has been implicated in cisplatin-induced renal injury. Losartan, an angiotensin II receptor blocker, may offer renal protection; however, its effects on apoptosis and regeneration in this context remain unclear. This study aimed to investigate the potential protective role of losartan against cisplatin-induced nephrotoxicity, specifically by assessing its impact on apoptosis and tubular regeneration. Fifteen female BALB/c mice were randomly assigned to three groups (n = 5 per group): Control, cisplatin (12.7 mg/kg, i.p., single dose), and cisplatin + losartan (10 mg/kg/day, oral). Losartan was administered for nine consecutive days, starting 4 days before cisplatin exposure. Histopathological examination, active caspase-3 immunostaining (for apoptosis), and 5-bromo-2-deoxyuridine (BrdU) labeling (for cell proliferation) were performed. Glomerular and tubular injury scores, caspase-3 H-scores, and BrdU-positive cell counts were statistically analyzed using the Kruskal–Wallis H and Mann–Whitney U tests. Cisplatin significantly increased glomerular (p = 0.006, p = 0.005, p = 0.006) and tubular injury scores (p = 0.008, p = 0.007, p = 0.007, p = 0.007, p = 0.007), elevated active caspase-3 expression (p = 0.002), and reduced BrdU-positive cell counts (p = 0.009) compared to control. Losartan co-treatment significantly reduced glomerular (p = 0.008, p = 0.005, p = 0.008) and tubular injury (p = 0.008, p = 0.008, p = 0.009, p = 0.008, v) and decreased caspase-3 expression (p = 0.009). Additionally, BrdU-positive cell counts were significantly higher in the cisplatin + losartan group compared to both control and cisplatin groups (p = 0.009), indicating enhanced regeneration. Losartan mitigates cisplatin-induced nephrotoxicity by suppressing apoptosis and promoting tubular regeneration. These findings support the potential therapeutic role of RAAS inhibition in preventing cisplatin-associated renal injury.