1. Cilostazol protects against gastric ulcers by regulating PPAR-γ, HO-1, PECAM-1, pErk-1, NF-κB, Bcl-2, and cleaved caspase-3 protein expression.
- Author
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El-Shitany NA, El-Saidy EA, El-Naggar ME, and Sokar SS
- Subjects
- Animals, Male, Rats, Heme Oxygenase (Decyclizing) metabolism, Anti-Ulcer Agents pharmacology, Mitogen-Activated Protein Kinase 1 metabolism, Anilides pharmacology, Mitogen-Activated Protein Kinase 3 metabolism, Tetrazoles pharmacology, Gastric Mucosa drug effects, Gastric Mucosa pathology, Gastric Mucosa metabolism, Phosphodiesterase 3 Inhibitors pharmacology, Apoptosis drug effects, Stomach Ulcer prevention & control, Stomach Ulcer chemically induced, Stomach Ulcer pathology, Stomach Ulcer metabolism, PPAR gamma metabolism, NF-kappa B metabolism, Ethanol toxicity, Caspase 3 metabolism, Cilostazol pharmacology, Proto-Oncogene Proteins c-bcl-2 metabolism
- Abstract
Millions of individuals worldwide, across all age groups, suffer from the widespread health issue of gastric ulcers. In many experiments, cilostazol (Cls), a phosphodiesterase-3 inhibitor, was recently shown to have anti-ulcer activity. Notably, Cls increases the expression and transcriptional activity of PPAR-γ in vitro and in vivo. This study aimed to evaluate the protective effect of Cls against ethanol-induced gastric ulcers and clarify the possible underlying mechanisms with an emphasis on the role of PPAR-γ. Male albino rats were treated with ethanol to induce gastric ulcers, or they were pretreated with Cls, omeprazole (Omp), GW9662, or Cls + GW9662 for 14 consecutive days before receiving ethanol. Cls protects against ethanol-induced gastric ulcers. Cls treatment significantly reduced ethanol-induced upregulation of the pro-inflammatory markers (IL-1β, IL-6, TNF-α, and NF-κB), MDA (a marker of lipid peroxidation), and caspase-3 and cleaved caspase-3 (apoptotic markers). On the other hand, Cls treatment counteracted ethanol-induced downregulation of PPAR-γ, pErk-1, HO-1 and GSH (antioxidant markers), PECAM-1 and NO (healing markers), and Bcl-2 (antiapoptotic marker). However, when combined with GW9662, a potent antagonist of PPAR-γ, Cls loses its effects. In conclusion, these results suggest that PPAR-γ and pErk-1 are essential for Cls's protective effects against ethanol-induced gastric ulcers., (© 2024. The Author(s).)
- Published
- 2024
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