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

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.