Effect of Sucralfate on Antibiotic Therapy for Helicobacter pylori Infection in Mice

Abstract

It has been documented that sucralfate, a basic aluminum salt, enhances the efficacies of antibiotics against Helicobacter pylori, resulting in eradication rates comparable to those associated with the use of proton pump inhibitors. However, its mechanism of action remains unclear. The aim of the present study was to investigate sucralfate's ability to complement antibiotic treatment of H. pylori infection in vivo. Four weeks following induced H. pylori infection, clarithromycin (CAM) and amoxicillin (AMPC) were administered orally to C57BL/6 mice for 5 days, both with and without sucralfate or lansoprazole. When sucralfate was concurrently given with CAM and AMPC at the maximum noninhibitory doses for the treatment of H. pylori infection, the bacterial clearance rates were comparable to those achieved by treatment with lansoprazole plus those antibiotics. The results of pharmacokinetic studies showed that lansoprazole delayed gastric clearance and accelerated the absorption of CAM, whereas sucralfate suppressed both gastric clearance and absorption. AMPC was undetectable in all samples. Scanning electron microscopy with a microscope to which a energy dispersive spectrometer was attached revealed that aluminum-containing aggregated substances coated the mucosa surrounding H. pylori in mice receiving sucralfate plus antibiotics, whereas the gastric surface and pits where H. pylori had attached were clearly visible in mice receiving lansoprazole plus antibiotics. The addition of sucralfate to the antibiotic suspension resulted in a more viscous mixture that bound to the H. pylori-infected mucosa and that inhibited the loss of CAM bioavailability in the acidic environment. Sucralfate delays gastric clearance of CAM and physically captures H. pylori through the creation of an adherent mucus, which leads to bacterial clearance.Sucralfate has traditionally been classified as a topical siteprotective or cytoprotective agent of ulcer-healing drugs with a high affinity for the gastric mucosa (18,28,29,45). The healing rates following sucralfate treatment of ulceration are comparable to those associated with the use of H 2 -receptor blockers and proton pump inhibitors (PPIs), and the relapse rates are low (16,17,20,21,23,37). Sucralfate binds to the gastric mucosa, which results in the inhibition of pepsin activity (5, 18, 32) and the enhancement of prostaglandin synthesis (5, 7, 32). Furthermore, sucralfate therapy increases gastroduodenal mucus and bicarbonate secretion (6, 7) and suppresses acid diffusion (3). On contact with gastric acid, sucralfate becomes a highly condensed, viscous substance with the capacity to buffer acid and adheres to the surfaces of normal and defective mucosae (29, 45). A complex of sucralfate and extracellular mucus forms an impenetrable barrier locally (15,45). The binding of sucralfate results from the electrostatic or ionic binding of the negatively charged molecules to the positively charged proteins in the mucus or ulcer crater (30). Although mucus glycoprotein is typically negatively c...

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