The dexpantenol's gastroprotective proprieties investigation use by NSAID-gastropathy model (preclinical study)

Introduction. The search for new gastroprotectors remains relevant, one of which could be dexpanthenol – a precursor of pantothenic acid that is non-toxic when taken orally. In Russia, systemic dexpanthenol preparations are not registered, and their use for treating acid-related diseases (ARDs) of the gastrointestinal tract isn’t known, and studying its gastroprotective properties when administered orally is promising.

Aim. Study of gastroprotective properties of dexpanthenol in oral administration using a model of gastropathy caused by non-steroidal anti-inflammatory drugs (NSAID-induced gastropathy) in preclinical research.

Materials and methods. The studies were conducted on 142 male outbred white rats weighing 220–280 g. The model used was NSAID-induced gastropathy with ulcerogenic agent sodium diclofenac, administered orally in a single dose of 50 mg/kg, euthanasia was performed 3 hours after administration via an overdose of chloroform anesthesia. Dexpanthenol was administered 1 hour before sodium diclofenac in a single oral dose in the form of an aqueous solution at doses of 400, 200, 40 mg/kg, and in the form of a developed 0.4 % gel (using high-viscosity chitosan as a gelling agent) at a dose of 7 mg/kg. Comparative drugs: dioxomethyltetrahydropyrimidine (syn. methyluracil) at a dose of 42 mg/kg, bismuth tripotassium dicitrate at a dose of 17 mg/kg. Both drugs were administered orally 1 hour before sodium diclofenac in a single dose. Evaluation criteria: number of animals with ulcers, number and area of ulcers on the gastric mucosa (GM) – determined using developed software written in Python with a graphical user interface (GUI). Calculation of the Pauls index and antiulcer activity index using known formulas, conducted histological examinations of the gastric mucosa with hematoxylin-eosin staining.

Results and discussion. It has been established that dexpanthenol provides a dose-dependent statistically significant reduction in the number and area of ulcers on the gastric mucosa, maximally by 2.7 times (at a dose of 40 mg/kg, 1,0 % aqueous solution, single oral administration) compared to the control group, and antiulcer activity index is 3.7, which exceeds the effectiveness of methyluracil. The 0,4 % dexpanthenol gel at a dose of 7 mg/kg demonstrated a significant reduction in ulcer area by 63 %, with an antiulcer activity index of 2.7, surpassing the effectiveness of bismuth tripotassium dicitrate. This is confirmed by signs of reduced inflammation intensity and activation of regeneration processes according to histological studies. The observed effects are likely attributed not only to dexpanthenol’s intrinsic activity but also to synergistic interactions with chitosan and the gastroprotective mucoadhesive properties of the gel formulation. The revealed gastroprotective activity of dexpanthenol aligns with its known mechanisms of action, including preservation of phospholipid bilayer integrity, modulation of mucin and tight junction (TJ) protein synthesis, regulation of nuclear transcription and apoptosis factors, growth factors, cytokines, and inflammatory mediators, cell division and cell differentiation.

Conclusion. For the first time, it has been proven that dexpanthenol, when administered orally in a single dose on the NSAID-gastropathy model, exhibit gastroprotective activity. It provides a significant statistically significant reduction in the number and area of ulcers compared to the control group. The antiulcer activity index is 3.7 (at a dose of 40 mg/kg, 1.0 % aqueous solution) surpassing the efficacy of methyluracil, 2,7 – when administered as a 0,4 % gel at 7 mg/kg (with chitosan as the gelling agent), these results were confirmed by histological examination and demonstrated superior effectiveness compared to bismuth tripotassium dicitrate.

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