Vincristine delays gastric emptying and gastrointestinal transit of liquid in awake rats

Abstract

We evaluated the effects of vincristine on the gastrointestinal (GI) motility of awake rats and correlated them with the course of vincristine-induced peripheral neuropathy. Vincristine or saline was injected into the tail vein of male Wistar rats (180-250 g) on alternate days: 50 μg/kg (5 doses, N = 10), 100 μg/kg (2, 3, 4 and 5 doses, N = 49) or 150 μg/kg (1, 2, or 5 doses, N = 37). Weight and stool output were measured daily for each animal. One day after completing the vincristine treatment, the animals were fasted for 24 h, gavage-fed with a test meal and sacrificed 10 min later to measure gastric emptying (GE), GI transit and colon weight. Sensory peripheral neuropathy was evaluated by hot plate testing. Chronic vincristine treatments with total cumulative doses of at least 250 μg/kg significantly decreased GE by 31-59% and GI transit by 55-93%. The effect of 5 doses of vincristine (150 μg/kg) on GE did not persist for more than 1 week. Colon weight increased after 2 and 5 doses of vincristine (150 μg/ kg). Fecal output decreased up to 48 h after the fifth dose of vincristine (150 μg/kg). Vincristine decreased the heat pain threshold 1 day after 5 doses of 50-100 μg/kg or after 3-5 doses of 150 μg/kg. This effect lasted for at least 2 weeks after the fifth dose. Chronic intravenous vincristine treatment delayed GE and GI transit of liquid. This effect correlated with the peak increase in colon weight but not with the pain threshold changes.