AUTHOR=Heleno Juliana Francisca Grossi , dos Santos Leticia Cristine Cardoso , Fontes Igor Campos , Paiva Silva Mirielly Ranny Almeida , Correia Lucas Barbosa , Silva Nayma Drielly Granato , Prazeres Pedro Henrique Dias Moura , Goulart Guimarães Pedro Pires , Gilroy Derek W. , Andrade Silvia Passos , Campos Paula Peixoto 
  
TITLE=L-Glutamine attenuates peritoneal fibrosis developed in 5-Fluorouracil-treated mice
  
JOURNAL=Experimental Biology and Medicine
  
VOLUME=Volume 251 - 2026
  
YEAR=2026
  
URL=https://www.ebm-journal.org/journals/experimental-biology-and-medicine/articles/10.3389/ebm.2026.10755
  
DOI=10.3389/ebm.2026.10755
  
ISSN=1535-3699
  
ABSTRACT=Peritoneal fibrosis is an adverse effect of cancer therapy leading to progressive organ failure. L-Glutamine supplementation has been shown to attenuate fibrosis and improve wound healing in several types of tissue injuries. The aim of this study was to evaluate the effects of this supplementation on key components of the peritoneal fibrovascular tissue induced by implants in mice treated with 5-Fluorouracil (5-FU) C57BL/6 mice received three intraperitoneal doses of immunosuppressant (60, 40, and 40 mg/kg) on non-consecutive days prior to implantation of polyether-polyurethane sponges into the peritoneal cavity. The group treated with L-Glutamine received 150 mg/kg/day for 7 days (oral gavage) starting 24 h after implantation and the control group received filtered water. Eight days after implantation, implants were removed and processed for inflammatory, angiogenic, and fibrogenic markers. Flow cytometry results showed that L-Glutamine decreased (48%) the frequency/influx of total intra-implant cells. The remaining cell population in the treated group had more neutrophils, lymphocytes, and macrophages than in the control. Immunohistochemistry analysis showed fewer Caspase-3-positive cells in the treated group. Myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAG) activities, TNF-α levels, and mast cell numbers were decreased in the implants of the L-Glutamine-treated group compared with the control. Similarly, angiogenesis (VEGF levels and number of blood vessels) was attenuated by L-Glutamine. Supplementation also decreased the amount of intra-implant collagen and TGF-β1 levels. These results indicate that L-Glutamine attenuates critical inflammatory-angiogenesis and profibrotic pathways involved in fibrosis development in immunosuppression conditions, supporting its potential as an adjunct therapeutic strategy for managing peritoneal healing in cancer.