Background Inflammatory bowel disease features chronic inflammation and epithelial barrier loss, driven by apoptosis, necroptosis, and oxidative stress. Dexpanthenol (DEX), a pantothenic acid derivative and CoA precursor, has antioxidant and tissue-protective properties, but its efficacy in colitis is unclear. Methods Thirty-two 8-week-old female Wistar albino rats were randomized to Control, Colitis, Colitis+DEX (500 mg/kg i.p. for 5 days after induction), or DEX-only (n = 8/group). Colitis was induced by intrarectal 4% acetic acid. Colonic tissues underwent H&E histology, immunohistochemistry for caspase-3, IL-6, and TNF-α, and qRT-PCR for p53, RIPK1, RIPK3, MLKL, BCL2, BAX, and caspase-9. Results Colitis caused severe mucosal ulceration, crypt destruction, and dense inflammatory infiltration, with upregulation of pro-apoptotic (p53, BAX, caspase-9) and necroptotic (RIPK1, RIPK3, MLKL) genes, and increased IL-6 and TNF-α. DEX significantly ameliorated these changes, restoring mucosal integrity, reducing inflammatory infiltrates, and improving crypt architecture. Molecularly, DEX downregulated p53, BAX, caspase-9, RIPK1, RIPK3, and MLKL, while immunohistochemistry showed decreased caspase-3, IL-6, and TNF-α versus untreated colitis. Conclusion DEX confers robust protection in acetic-acid colitis by modulating apoptotic and necroptotic pathways and suppressing pro-inflammatory cytokines. These preclinical findings support DEX as a barrier-centric, promising epithelial-protective strategy warranting further evaluation for inflammatory bowel disease, including pediatric contexts. Impact <UnorderedList Mark="Bullet"> <ItemContent> Key message: In a young-rat acetic-acid colitis model, dexpanthenol (DEX) preserved mucosal architecture and suppressed inflammation by modulating epithelial cell-death programs. </ItemContent> <ItemContent> Added value: DEX simultaneously downregulated apoptotic (p53, BAX, Caspase-9) and necroptotic (RIPK1, RIPK3, MLKL) pathways while restoring BCL2—a dual mechanism not previously reported in colitis models. </ItemContent> <ItemContent> Impact: Suggests that DEX may function as a barrier-centric protective strategy, potentially complementing biologics that target downstream cytokines (e.g., TNF-α, IL-6). </ItemContent> <ItemContent> Clinical outlook: Supports translational evaluation—especially in pediatric IBD and biologic non-responders—where durable epithelial protection is needed. </ItemContent> </UnorderedList>

Protective effects of dexpanthenol on experimental colitis in young rats: modulation of p53/BAX/BCL2 and RIPK1/RIPK3/MLKL signaling with anti-inflammatory activity

期刊论文
发表日期：

2026年7月1日

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Abdulkerim Elmas,
Halil Asci,
Muhammet Yusuf Tepebasi,
Orhan Berk Imeci,
Abdurrahman Gulal,
Muhammed Burak Selver,
Mustafa Akcam,
Ozlem Ozmen

摘要

Background

Inflammatory bowel disease features chronic inflammation and epithelial barrier loss, driven by apoptosis, necroptosis, and oxidative stress. Dexpanthenol (DEX), a pantothenic acid derivative and CoA precursor, has antioxidant and tissue-protective properties, but its efficacy in colitis is unclear.

Methods

Thirty-two 8-week-old female Wistar albino rats were randomized to Control, Colitis, Colitis+DEX (500 mg/kg i.p. for 5 days after induction), or DEX-only (n = 8/group). Colitis was induced by intrarectal 4% acetic acid. Colonic tissues underwent H&E histology, immunohistochemistry for caspase-3, IL-6, and TNF-α, and qRT-PCR for p53, RIPK1, RIPK3, MLKL, BCL2, BAX, and caspase-9.

Results

Colitis caused severe mucosal ulceration, crypt destruction, and dense inflammatory infiltration, with upregulation of pro-apoptotic (p53, BAX, caspase-9) and necroptotic (RIPK1, RIPK3, MLKL) genes, and increased IL-6 and TNF-α. DEX significantly ameliorated these changes, restoring mucosal integrity, reducing inflammatory infiltrates, and improving crypt architecture. Molecularly, DEX downregulated p53, BAX, caspase-9, RIPK1, RIPK3, and MLKL, while immunohistochemistry showed decreased caspase-3, IL-6, and TNF-α versus untreated colitis.

Conclusion

DEX confers robust protection in acetic-acid colitis by modulating apoptotic and necroptotic pathways and suppressing pro-inflammatory cytokines. These preclinical findings support DEX as a barrier-centric, promising epithelial-protective strategy warranting further evaluation for inflammatory bowel disease, including pediatric contexts.

Impact

Key message: In a young-rat acetic-acid colitis model, dexpanthenol (DEX) preserved mucosal architecture and suppressed inflammation by modulating epithelial cell-death programs.

Added value: DEX simultaneously downregulated apoptotic (p53, BAX, Caspase-9) and necroptotic (RIPK1, RIPK3, MLKL) pathways while restoring BCL2—a dual mechanism not previously reported in colitis models.

Impact: Suggests that DEX may function as a barrier-centric protective strategy, potentially complementing biologics that target downstream cytokines (e.g., TNF-α, IL-6).

Clinical outlook: Supports translational evaluation—especially in pediatric IBD and biologic non-responders—where durable epithelial protection is needed.