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<p>Gastric ulcers, a prevalent gastrointestinal disorder marked by mucosal damage, sometimes resist complete healing with existing therapies. This study evaluated the therapeutic potential of tadalafil, both alone and in combination with omeprazole, in a rat model of acetic acid-induced chronic gastric ulcer. Male Wistar rats were divided into six groups: sham, model, omeprazole (40&#xa0;mg/kg), low-dose tadalafil (20&#xa0;mg/kg), high-dose tadalafil (40&#xa0;mg/kg), and a combination of tadalafil (20&#xa0;mg/kg) and omeprazole (40&#xa0;mg/kg). Gastric ulcers were induced using acetic acid, followed by daily oral treatments for 12&#xa0;days. Parameters assessed included ulcer size, lipid peroxidation, and the expression of nuclear factor kappa B (NF-κB, a protein complex regulating inflammation), vimentin, and proliferating cell nuclear antigen (PCNA, a marker of cell proliferation). Additionally, mRNA levels of AMP-activated protein kinase (AMPK), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS), along with tissue nitric oxide (NO) metabolites (NOx), were measured. Low-dose tadalafil (20&#xa0;mg/kg) significantly decreased ulcer size and inflammation while enhancing cell proliferation, independent of AMPK mRNA change. In contrast, high-dose tadalafil (40&#xa0;mg/kg) failed to confer similar benefits, exacerbating inflammation and increasing NOx levels. The combination of tadalafil and omeprazole demonstrated efficacy comparable to low-dose tadalafil alone, sustaining eNOS expression and suggesting potential synergistic effects for long-term healing. However, no significant synergy was observed during the 12-day treatment period. These findings highlight the importance of dose optimization and suggest the potential repurposing of phosphodiesterase type 5 inhibitors, such as tadalafil, for managing gastrointestinal disorders.</p>

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Therapeutic potential of tadalafil in acetic acid-induced gastric ulcer in rats: mechanisms and outcomes

  • 期刊论文

  • 发表日期：

    2025年6月18日

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  • Behzad Mesbahzadeh,
  • Negar Moodi,
  • Mohammadmehdi Hassanzadeh-Taheri,
  • Mona Saheli,
  • Mehran Hosseini

摘要

Gastric ulcers, a prevalent gastrointestinal disorder marked by mucosal damage, sometimes resist complete healing with existing therapies. This study evaluated the therapeutic potential of tadalafil, both alone and in combination with omeprazole, in a rat model of acetic acid-induced chronic gastric ulcer. Male Wistar rats were divided into six groups: sham, model, omeprazole (40 mg/kg), low-dose tadalafil (20 mg/kg), high-dose tadalafil (40 mg/kg), and a combination of tadalafil (20 mg/kg) and omeprazole (40 mg/kg). Gastric ulcers were induced using acetic acid, followed by daily oral treatments for 12 days. Parameters assessed included ulcer size, lipid peroxidation, and the expression of nuclear factor kappa B (NF-κB, a protein complex regulating inflammation), vimentin, and proliferating cell nuclear antigen (PCNA, a marker of cell proliferation). Additionally, mRNA levels of AMP-activated protein kinase (AMPK), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS), along with tissue nitric oxide (NO) metabolites (NOx), were measured. Low-dose tadalafil (20 mg/kg) significantly decreased ulcer size and inflammation while enhancing cell proliferation, independent of AMPK mRNA change. In contrast, high-dose tadalafil (40 mg/kg) failed to confer similar benefits, exacerbating inflammation and increasing NOx levels. The combination of tadalafil and omeprazole demonstrated efficacy comparable to low-dose tadalafil alone, sustaining eNOS expression and suggesting potential synergistic effects for long-term healing. However, no significant synergy was observed during the 12-day treatment period. These findings highlight the importance of dose optimization and suggest the potential repurposing of phosphodiesterase type 5 inhibitors, such as tadalafil, for managing gastrointestinal disorders.