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Purpose <p>Irinotecan is widely used in metastatic colorectal cancer, but its clinical utility is limited by gastrointestinal toxicity, particularly intestinal mucositis, for which effective therapies are lacking. This study evaluated the protective effects of pioglitazone, a thiazolidinedione PPAR-γ agonist, against irinotecan-induced mucositis in female Swiss mice.</p> Methods <p>Mucositis was induced by irinotecan (75&#xa0;mg/kg, i.p., for 4 days), followed by pioglitazone treatment (3, 10, and 30&#xa0;mg/kg orally, or 3&#xa0;mg/kg intraperitoneally) for 7 days.</p> Results <p>Pioglitazone at 30&#xa0;mg/kg (p.o.) significantly reduced diarrhea score and partially restored leukocyte counts and spleen weight, while also improving duodenal weight. Histological analysis revealed preservation of villus structure, crypt integrity, and goblet cell numbers, with reduced inflammatory infiltration and mucosal vacuolization. At the biochemical level, pioglitazone restored superoxide dismutase (SOD) activity, normalized glutathione S-transferase (GST) activity, and markedly decreased myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) activities, although glutathione (GSH) remained depleted and nitrite levels elevated.</p> Conclusions <p>Collectively, these findings demonstrate that pioglitazone at 30&#xa0;mg/kg (p.o.) attenuates key clinical, histological, and inflammatory alterations and modulates redox-related parameters associated with irinotecan-induced mucositis. Pioglitazone thus emerges as a promising candidate for repurposing as an adjuvant therapy to improve chemotherapy tolerability in colorectal cancer.</p>

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Pioglitazone Mitigates Irinotecan-Induced Intestinal Mucositis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月13日

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  • Ian Passos Alves,
  • Thiago Colpo,
  • Mariana Zanovello,
  • Rita de Cassia Melo Vilhena de Andrade Fonseca da Silva,
  • Anelize Dada,
  • Sabrina Lucietti Dick,
  • Priscila de Souza,
  • Thaise Boeing

摘要

Purpose

Irinotecan is widely used in metastatic colorectal cancer, but its clinical utility is limited by gastrointestinal toxicity, particularly intestinal mucositis, for which effective therapies are lacking. This study evaluated the protective effects of pioglitazone, a thiazolidinedione PPAR-γ agonist, against irinotecan-induced mucositis in female Swiss mice.

Methods

Mucositis was induced by irinotecan (75 mg/kg, i.p., for 4 days), followed by pioglitazone treatment (3, 10, and 30 mg/kg orally, or 3 mg/kg intraperitoneally) for 7 days.

Results

Pioglitazone at 30 mg/kg (p.o.) significantly reduced diarrhea score and partially restored leukocyte counts and spleen weight, while also improving duodenal weight. Histological analysis revealed preservation of villus structure, crypt integrity, and goblet cell numbers, with reduced inflammatory infiltration and mucosal vacuolization. At the biochemical level, pioglitazone restored superoxide dismutase (SOD) activity, normalized glutathione S-transferase (GST) activity, and markedly decreased myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) activities, although glutathione (GSH) remained depleted and nitrite levels elevated.

Conclusions

Collectively, these findings demonstrate that pioglitazone at 30 mg/kg (p.o.) attenuates key clinical, histological, and inflammatory alterations and modulates redox-related parameters associated with irinotecan-induced mucositis. Pioglitazone thus emerges as a promising candidate for repurposing as an adjuvant therapy to improve chemotherapy tolerability in colorectal cancer.