Leptin accelerates enterocyte turnover during methotrexate-induced intestinal mucositis in a rat model
Authors: Arnold G Coran
Dan Shteinberg
Michael Lurie
Benno M Ure
Ron Shaoul
Igor Sukhotnik
Rahel Karry
Jorge G Mogilner
Journal: Cancer biology & therapy (2009)
Discipline: CLINICAL MEDICINE
Keywords: Gastrointestinal mucositis; Leptin; Methotrexate; Intestinal damage; Cell proliferation
Affiliations: The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Laboratory of intestinal adaptation and recovery, Bnai Zion Medical Center, Haifa, Israel. 

Abstract:  Gastrointestinal mucositis occurs as a consequence of cytotoxic treatment. In the present study, we tested whether leptin can protect gut epithelial cells from methotrexate (MTX)-induced intestinal damage. Non-pretreated and pretreated with MTX Caco-2 cells were incubated with increasing concentrations of leptin for 24 h. Cell proliferation and apoptosis were assessed using FACS analysis. Adult rats were divided into three experimental groups: Control rats; MTX-rats were treated with a single dose of MTX, and MTX-LEP rats were also treated with leptin for 3 d. Intestinal mucosal damage (Park score), mucosal structural changes (bowel and mucosal weight, mucosal DNA and protein content, villus height and crypt depth), enterocyte proliferation, and enterocyte apoptosis were measured at sacrifice. RT-PCR was used to determine the level of bax and bcl-2 mRNA expression. In the vitro experiment, treatment with leptin of Caco-2 cells pre-treated with MTX resulted in a significant stimulation of cell proliferation and inhibition of cell apoptosis in a dose-dependent manner. In the vivo experiment, MTX-LEP rats demonstrated a greater jejunal and ileal bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, as well as a greater enterocyte proliferation index compared to MTX-animals. MTX-LEP rats also showed a trend toward an increase in enterocyte apoptosis that was accompanied by an increase in bax mRNA and decrease in bcl-2 mRNA expression. In conclusion, leptin enhances proliferation and decreases apoptosis in Caco-2 cells pretreated with MTX. In a rat model of MTX-induced mucositis, treatment with leptin improves intestinal recovery and enhances enterocyte turnover. 

Retracted: No

PubPeer comments:
 This paper appears to be part of a set of at least 13 papers that appear to share immunohistochemistry images. All papers list Igor Sukhotnik as an author and they span a period of 12 years. The images do not always represent the same experiments. 1. Mogilner JG et al., Journal of Pediatric Surgery (2007), DOI: 10.1016 j.jpedsurg.2007.03.035 2. Sukhotnik I et al., Cancer Biology Therapy (2009), DOI: 10.4161 cbt.8.10.8128 3. Sukhotnik I et al., Journal of Pediatric Surgery (2011), DOI: 10.1016 j.jpedsurg.2010.09.051 4. Ben-Lulu S et al., PLOS ONE (2012), DOI: 10.1371 journal.pone.0045221 5. Koppelman T et al., BMC Gastroenterology (2012), DOI: 10.1186 1471-230X-12-41 6. Koppelman T et al., British Journal of Nutrition (2013), DOI: 10.1017 S0007114512000542 7. Swaid F et al., Nutrition Metabolism (2013), DOI: 10.1186 1743-7075-10-53 8. Sukhotnik I et al., Nutrition Metabolism (2014), DOI: 10.1186 1743-7075-11-17 9. Sukhotnik I et al., PLOS ONE (2014), DOI: 10.1371 journal.pone.0110675 10. Sukhotnik I et al., European Journal of Pediatric Surgery (2016), DOI: 10.1055 s-0036-1587588 11. Ben Shahar Y et al., European Journal of Pediatric Surgery (2016), DOI: 10.1055 s-0035-1559886 12. Sukhotnik I et al., Food Nutrition Research (2018), DOI: 10.29219 fnr.v62.1327 13. Ben-Shahar Y et al., European Journal of Pediatric Surgery (2019), DOI: 10.1055 s-0039-1700550 Here are three collages of the IHC figures from these papers, with boxes of the same color highlighting panels that look more similar than expected. ![file] ![file] ![file] , 
 This paper is one of a set of four papers, all by Sukhotnik et al., that appear to contain the highly similar flow cytometry panels. Boxes of the same color highlight panels that look very similar. They do not all appear to show the same experiment, in particular the panels labeled with red boxes. The four papers span a period of six years and are: * Sukhotnik et al., Apoptosis (2008) 13:1344u20131355, DOI: 10.1007 s10495-008-0258-x * Sukhotnik et al., Pediatr Surg Int (2008) 24:1303u20131311, DOI: 10.1007 s00383-008-2271-0 * Sukhotnik et al., Cancer Biology Therapy (2009), DOI: 10.4161 cbt.8.10.8128 * Sukhotnik et al., PLOS ONE (2014), DOI: 10.1371 journal.pone.0110675 ![file] ,