title: Efficacy and pharmacological mechanism of pronase-enhanced low-dose antibiotics for Helicobacter pylori eradication.
abstract: This study examined the efficacy and pharmacological mechanism of pronase-assisted low-dose antibiotics for eradication of Helicobacter pylori. Mongolian gerbils infected with H. pylori received 7-day treatment (omeprazole, different concentrations of pronase, amoxicillin, and clarithromycin), and the efficacy was assessed using the eradication rate and the colonization of H. pylori. In Mongolian gerbils orally administered pronase, the thickness of the gastric mucous layer (GML) was examined using immunohistochemical and alcian blue staining, and the concentrations of amoxicillin in gastric tissue and serum were detected using high-performance liquid chromatography (HPLC). The eradication rates were 80.0% (12/15) in the high-pronase quadruple group (HPQG) and 86.7% (13/15) in the high-antibiotic group (HAG) (P = 1.000). The antibiotic dose in the HPQG was only 1/20 that in the HAG. Thirty minutes after oral treatment with pronase, the sticky protein of the GML was hydrolyzed, and the GML became thinner. Higher amoxicillin concentrations in both the gastric tissue and serum were observed in the pronase group than in the Am10 group. The concentration of amoxicillin in the Am10-plus-Pr108 group in gastric tissue was 3.8 times higher than in the Am10 group in 5 min. Together, these data suggest that pronase significantly reduced the dose of antibiotics used in H. pylori eradication. The pharmacological mechanism is likely pronase removal of the mucus layer, promoting chemical factor (i.e., gastric acid and pepsinogen) distribution and increasing the antibiotic concentrations in the deep GML, which acted on H. pylori collectively. Thus, pronase may enhance the level of antibiotics for eradication of H. pylori in the clinic.
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Kai Y
authors.initials: KY
authors.lastname: Liu
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Fang C
authors.initials: FC
authors.lastname: Du
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Wei J
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Hong W
authors.initials: HW
authors.lastname: Sun
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Beijing Tide Pharmaceutical Co., Ltd., Beijing, China.
authors.forename: Le L
authors.initials: le L
authors.lastname: Gan
authors.affiliation: Beijing Tide Pharmaceutical Co., Ltd., Beijing, China.
authors.forename: Zhi Y
authors.initials: ZY
authors.lastname: Yue
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China guogang7001@163.com qmzou2007@163.com.
authors.forename: Quan M
authors.initials: QM
authors.lastname: Zou
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, China guogang7001@163.com qmzou2007@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
mesh_terms: D000658:Amoxicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D017291:Clarithromycin / Q000494:pharmacology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D009853:Omeprazole / Q000494:pharmacology; D011402:Pronase / Q000494:pharmacology*; D013270:Stomach / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D000658:Amoxicillin; D011402:Pronase; D017291:Clarithromycin; D009853:Omeprazole