PURPOSE: High doses of anticancer drugs often damage the intestinal mucosa. The purpose of the present study was to examine the effect of glutamine on mucosal damage induced by cyclophosphamide in a rat model, and to elucidate the mechanisms responsible for its protective effects. METHOD: Rats were randomly assigned to one of the three experimental groups. Group A (control) (n = 8): intraperitoneal injection of saline, group B (n = 8): intraperitoneal injection of cyclophosphamide (300 mg/kg), group C (n = 8): intraperitoneal injection of cyclophosphamide (300 mg/kg) and oral glutamine (1.0 g/kg). After 3 days, the ileal segment was removed for morphological and the biochemical analyses. We also evaluated the level of mucosal apoptosis by the TUNEL method and enterocyte proliferation using bromodeoxyuridine (BrdU). RESULTS: Mucosal atrophy was observed in group B but not in groups A or C. The mucosal wet weight, protein and glutathione levels were significantly decreased in group B compared with group A, and were increased significantly in group C compared with group B. While enterocyte proliferation significantly decreased and the apoptotic index significantly increased in group B compared with group A, a significant increase in the enterocyte proliferation and a significant decrease in apoptosis were observed in group C compared with group B. CONCLUSIONS: Glutamine prevented intestinal mucosal injury induced by cyclophosphamide via increased glutathione, decreased apoptosis and increased proliferation of intestinal epithelial cells.
PURPOSE: High doses of anticancer drugs often damage the intestinal mucosa. The purpose of the present study was to examine the effect of glutamine on mucosal damage induced by cyclophosphamide in a rat model, and to elucidate the mechanisms responsible for its protective effects. METHOD:Rats were randomly assigned to one of the three experimental groups. Group A (control) (n = 8): intraperitoneal injection of saline, group B (n = 8): intraperitoneal injection of cyclophosphamide (300 mg/kg), group C (n = 8): intraperitoneal injection of cyclophosphamide (300 mg/kg) and oral glutamine (1.0 g/kg). After 3 days, the ileal segment was removed for morphological and the biochemical analyses. We also evaluated the level of mucosal apoptosis by the TUNEL method and enterocyte proliferation using bromodeoxyuridine (BrdU). RESULTS:Mucosal atrophy was observed in group B but not in groups A or C. The mucosal wet weight, protein and glutathione levels were significantly decreased in group B compared with group A, and were increased significantly in group C compared with group B. While enterocyte proliferation significantly decreased and the apoptotic index significantly increased in group B compared with group A, a significant increase in the enterocyte proliferation and a significant decrease in apoptosis were observed in group C compared with group B. CONCLUSIONS:Glutamine prevented intestinal mucosal injury induced by cyclophosphamide via increased glutathione, decreased apoptosis and increased proliferation of intestinal epithelial cells.
Authors: P K Smith; R I Krohn; G T Hermanson; A K Mallia; F H Gartner; M D Provenzano; E K Fujimoto; N M Goeke; B J Olson; D C Klenk Journal: Anal Biochem Date: 1985-10 Impact factor: 3.365
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Authors: Carlos Vinicius D da Rosa; Silvia C S F Azevedo; Roberto B Bazotte; Rosane M Peralta; Nilza C Buttow; Maria Montserrat D Pedrosa; Vilma A F de Godoi; Maria Raquel M Natali Journal: PLoS One Date: 2015-12-14 Impact factor: 3.240