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

Abstract

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. 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. 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. 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. 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. 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.