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.

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come

“…Such substitution led to a reduction in both the liposomal vincristine leakage rate and hydrolysis rate by 1.42-fold and 100-fold in vitro, respectively and a ;75% retention of encapsulated vincristine within liposomes 24 hours after an intravenous injection into mice (Boman et al, 1994(Boman et al, , 1995Webb et al, 1995;Johnstone et al, 2001;Krishna et al, 2001). Furthermore, the mean particle size of ;100 nm helped prolong the circulation time of liposomal vincristine (Peixoto Júnior et al, 2009;Thomas et al, 2009;Silverman and Deitcher, 2013). A negligible level of bovine and human plasma protein binding was also observed on the surface of liposomal vincristine during in vitro studies, which was probably due to the neutral charge of the sphingomyelin/cholesterol composition and a tight lipid arrangement Oja et al, 1996).…”

Sensory and inflammatory colonic changes induced by vincristine in distinct rat models of colitis

“…Our results also reveal that vincristine, a chemotherapy agent that is also known to induce peripheral neuropathy (Authier et al ., ; Peixoto Junior et al ., ), enhanced the somatic hypersensitivity induced by the acute TNBS colitis, further decreasing the latency of thermal paw withdrawal response. These results suggest that acute colitis induced by TNBS induces changes in the peripheral nervous system excitability.…”

“…(). It has been previously used in our laboratory to induce somatic changes in rats (Peixoto Junior et al ., ). One of these subgroups ( N = 6) was submitted to rectal enema with water, and the other two subgroups were subjected to colitis induction with TNBS ( N = 6) or mustard oil ( N = 5).…”

The role of nitric oxide in alendronate-mediated acceleration of gastric emptying and gastrointestinal transit in rats

“…Intestinal transit was calculated for gut bowel segments by dividing the amount of phenol red recovered from a given segment by the amount of phenol red recovered from all three segments, and it is expressed as fractional dye retention (%) (Peixoto-Junior et al, 2009).…”