Reduced absorption of long-chain fatty acids during methotrexate-induced gastrointestinal mucositis in the rat

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• 作者：Margot Fijlstra^a ; ^b ; ^{m.fijlstra@med.umcg.nl} ; Wim J.E. Tissing^b ; ^{w.j.e.tissing@umcg.nl} ; Frans Stellaard^c ; ^{f.stellaard@med.umcg.nl} ; Henkjan J. Verkade^a ; ^{h.j.verkade@umcg.nl} ; Edmond H.H.M. Rings^a ; ^{e.h.h.m.rings@umcg.nl}
• 关键词：Gastrointestinal mucositis ; Long-chain fatty acids ; Nutrient absorption ; Liver fatty acid appearance ; Chemotherapy ; Citrulline
• 刊名：Clinical Nutrition
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：32
• 期：3
• 页码：452-459
• 全文大小：800 K

文摘

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Summary

Background & aims

Patients with chemotherapy-induced gastrointestinal mucositis suffer from weight loss and possibly malabsorption. Since long-chain fatty acids serve important functions in the body, we aimed to determine the intestinal capacity of fat absorption in rats with and without methotrexate-induced mucositis.

Methods

Four days after intravenous injection with methotrexate (60?mg/kg) or saline, rats received saturated ([U-¹³C]palmitic acid) and unsaturated ([U-¹³C]linoleic acid) fatty acids dissolved in oil, either as a single bolus by oral gavage or by continuous intraduodenal infusion. We determined plasma and liver label concentrations at specific time points.

Results

We confirmed methotrexate-induced mucositis by villus atrophy using microscopy. Methotrexate treatment severely reduced the appearance of [U-¹³C]palmitic- and [U-¹³C]linoleic acid in plasma and liver, compared to controls, either when administered as a bolus or continuously (all at least??63 % , P?<?0.05). Liver [U-¹³C]palmitic acid appearance was higher than [U-¹³C]linoleic acid appearance, either when administered as a bolus (2.8-fold, P?<?0.01) or continuously (5.7-fold, P?<?0.01).

Conclusions

The intestinal capacity to absorb long-chain fatty acids is severely reduced in rats with methotrexate-induced mucositis. Continuous administration does not overcome this impairment. The liver takes up and/or retains mainly saturated fatty acids during mucositis.