Effect of a Glutamine‐Supplemented Enteral Diet on Methotrexate‐Induced Enterocolitis

Abstract

Administration of an elemental diet to rats given methotrexate (MTX), 20 mg/kg intraperitoneally (ip), results in 100% mortality from severe enterocolitis. Previous studies indicate that glutamine (GLN), which is not present in elemental diets, is the preferred oxidative substrate for the gut and may facilitate intestinal recovery after injury. This study investigated the effects of a glutamine-supplemented elemental diet (GLN-ED) on nutritional status, intestinal morphometry, bacterial translocation and survival in this lethal model of intestinal injury. Three experiments were performed. In the first experiment, rats received an intragastric elemental diet supplemented with either 2% GLN or an equivalent amount of glycine (Control). After 4 days animals received either MTX, 20 mg/kg ip, or saline ip and were killed 3 days later. The GLN-ED resulted in significantly decreased weight loss, improved nitrogen retention, and increased mucosal weight, protein, and DNA content of the jejunum and colon. In the second experiment rats were assigned to diet as in the first experiment, but all animals received MTX. Control diet animals died within 120 hrs of MTX administration. The GLN-ED group had significantly longer survival time and decreased mortality. In the third experiment animals were assigned to diet and MTX as in the first experiment. Ninety-six hrs later aortic blood cultures revealed enteric bacteremia in animals administered MTX. GLN-ED resulted in a significant reduction in the incidence of bacteremia. These experiments showed that a GLN-ED significantly improved nutritional status, decreased intestinal injury, decreased bacterial translocation, and resulted in improved survival in a lethal model of enterocolitis.

Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation

“…The latter showed superior survival after oral vs parenteral glutamine. 27 Oral glutamine was also associated with improved survival at day 28 in our study. One possible explanation is that although stomatitis may be worse in matched sibling donor allogeneic patients receiving glutamine and methotrexate, the gut may be protected.…”

Treatment-induced mucositis: an old problem with new remedies

“…There is a suggestion that the addition of azelastine reduced mucositis (Osaki et al, 1994). Feeding experimental animals additional glutamine seems to reduce the effects of cytotoxic agents, particularly 5-fluorouracil and methotrexate (O'Dwyer et al, 1987;Fox et al, 1988). Bowel ulceration caused by these anti-metabolites and corresponding bacteraemia was reduced (Fox et al, 1988).…”

“…Feeding experimental animals additional glutamine seems to reduce the effects of cytotoxic agents, particularly 5-fluorouracil and methotrexate (O'Dwyer et al, 1987;Fox et al, 1988). Bowel ulceration caused by these anti-metabolites and corresponding bacteraemia was reduced (Fox et al, 1988). However, when additional glutamine supplements were given to patients suffering from gastrointestinal cancer, treated by 5-fluorouracil and folinic acid in a placebo-controlled double-blind trial, there was no difference in the degree of observed oral mucositis (Jebb et al, 1994).…”

Oral glutamine in paediatric oncology patients: a dose finding study

“…Although animal data on the effects of glutamine supplementation are fairly extensive (Fox et al, 1987(Fox et al, , 1988(Fox et al, , 1989Burke et al, 1989;Jacobs et al, 1987;Wang et al, 1988) clinical studies are still quite limited (Smith, 1997). However, no toxic effects of glutamine given either parenterally or enterally have been demonstrated (Ziegler et al, 1992;van Zaanen et al, 1994;Skubitz & Anderson, 1996).…”