Lactulose in Vincristine‐induced Constipation

Ac, Harris; Jm, Jackson

doi:10.5694/j.1326-5377.1977.tb114646.x

Cited by 19 publications

(8 citation statements)

References 7 publications

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“…In fact, the motility curve of caecum looked very similar (parallel) to that in control animals both 24 and 48 h after vincristine (0.5 mg/kg), but displaced to the right, further suggesting that small intestinal transit was delayed. Interestingly, in spite of the fact that caecum filled adequately, there was a complete absence of stained fecal pellets in vincristine-treated rats for the whole duration of the radiologic study when it was performed 24 h after the antitumoral drug, suggesting that vincristine directly suppressed motility in colorectum, which is in accordance with the reports of constipation associated to treatment with vinca alkaloids, in both animals and humans (Harris and Jackson, 1977 ; Garewal and Dalton, 1985 ; Ikehara, 1992 ; Leker et al, 1997 ; Chae et al, 1998 ; Wang et al, 2000 ; Essa et al, 2014 ; Yasu et al, 2016 ).…”

Section: Discussionsupporting

confidence: 89%

“…Very few agents have been tested in vincristine-induced gastrointestinal ileus and most references are case reports with low numbers of subjects (Harris and Jackson, 1977 ; Jackson et al, 1982 ; Garewal and Dalton, 1985 ; Ikehara, 1992 ; Tsukamoto et al, 2011 ; Essa et al, 2014 ; Mason et al, 2014 ). To the best of our knowledge, the possible role of cannabinoids has never before been tested either in experimental animals or in the clinic.…”

Section: Discussionmentioning

confidence: 99%

“…The main side effect of vincristine is a dose dependent and cumulative peripheral neuropathy. Paresthesias, loss of tendon reflexes, and progressive weakness are the most common clinical features, although autonomic dysfunctions, including gastrointestinal disturbances, might occur (Rosenthal and Kaufman, 1974 ; Harris and Jackson, 1977 ; Chae et al, 1998 ; Wang et al, 2000 ). Indeed, gastrointestinal complications may be present in up to 30–40% of patients receiving vincristine and the earliest symptoms may include colicky abdominal pain, constipation, and adynamic or paralytic ileus as the major manifestations.…”

Section: Introductionmentioning

confidence: 99%

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Involvement of Cannabinoid Signaling in Vincristine-Induced Gastrointestinal Dysmotility in the Rat

et al. 2017

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Background: In different models of paralytic ileus, cannabinoid receptors are overexpressed and endogenous cannabinoids are massively released, contributing to gastrointestinal dysmotility. The antitumoral drug vincristine depresses gastrointestinal motility and a similar mechanism could participate in this effect. Therefore, our aim was to determine, using CB1 and CB2 antagonists, whether an increased endocannabinoid tone is involved in vincristine-induced gastrointestinal ileus.Methods: First, we confirmed the effects of vincristine on the gut mucosa, by conventional histological techniques, and characterized its effects on motility, by radiographic means. Conscious male Wistar rats received an intraperitoneal injection of vincristine (0.1–0.5 mg/kg), and barium sulfate (2.5 ml; 2 g/ml) was intragastrically administered 0, 24, or 48 h later. Serial X-rays were obtained at different time-points (0–8 h) after contrast. X-rays were used to build motility curves for each gastrointestinal region and determine the size of stomach and caecum. Tissue samples were taken for histology 48 h after saline or vincristine (0.5 mg/kg). Second, AM251 (a CB1 receptor antagonist) and AM630 (a CB2 receptor antagonist) were used to determine if CB1 and/or CB2 receptors are involved in vincristine-induced gastrointestinal dysmotility.Key results: Vincristine induced damage to the mucosa of ileum and colon and reduced gastrointestinal motor function at 0.5 mg/kg. The effect on motor function was particularly evident when the study started 24 h after administration. AM251, but not AM630, significantly prevented vincristine effect, particularly in the small intestine, when administered thrice. AM251 alone did not significantly alter gastrointestinal motility.Conclusions: The fact that AM251, but not AM630, is capable of reducing the effect of vincristine suggests that, like in other experimental models of paralytic ileus, an increased cannabinoid tone develops and is at least partially responsible for the alterations induced by the antitumoral drug on gastrointestinal motor function. Thus, CB1 antagonists might be useful to prevent/treat ileus induced by vincristine.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Involvement of Cannabinoid Signaling in Vincristine-Induced Gastrointestinal Dysmotility in the Rat

et al. 2017

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“…This is likely to be due to the concomitant use of lenalidomide and vincristine. Vincristine is associated with the development of autonomic neuropathy that may present as severe constipation [14]. Constipation was seen in 30 % of patients treated with lenalidomide and rituximab for relapsed/refractory lymphoma [15].…”

Section: Tolerance and Safetymentioning

confidence: 99%

L-PROBe: A Novel Non-anthracycline Combination Chemotherapy Regimen for Aggressive B Cell Non-Hodgkin Lymphoma in Elderly Patients

Law

Prakash

Khadwal

et al. 2016

Indian J Hematol Blood Transfus

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The management of aggressive B cell lymphomas in elderly patients is associated with poor tolerability of commonly used chemotherapeutic agents. The safety and tolerability of a novel combination chemotherapy regimen utilizing rituximab, lenalidomide, bendamustine, vincristine and prednisolone was assessed in a series of elderly patients with new onset or relapsed/refractory aggressive B cell lymphoma and inability to receive conventional chemotherapy due to poor performance status and/or significant comorbidities. Ten patients (7 male, 3 female) with a median age of 72 years (range 58-79 years) received therapy with lenalidomide (10 mg/day on days 1-14), rituximab (375 mg/m on day 1), bendamustine (90 mg/m on days 1 and 2), vincristine (1.4 mg/m on day 1) and prednisolone (60 mg/m/day on days 1-5) with cycles repeated every 28 days. Grade 3/4 hematological toxicities included neutropenia (30 %), anemia (30 %) and thrombocytopenia (10 %). An overall response rate of 40 % was observed with a median survival of 120 days (range 14-286 days). Three of the patients who responded achieved complete remission at the end of six cycles of therapy. This combination chemotherapy appears to be well tolerated and effective in elderly patients with poor performance status. Larger controlled studies are indicated to clearly demonstrate applicability of this novel regimen.

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“…4,5 Paresthesia, loss of tendon reflexes and progressive weakness are the most common clinical features, although autonomic dysfunctions, including gastrointestinal (GI) disturbances, may also occur. [6][7][8][9] In fact, 30%-40% of patients receiving vincristine may develop GI complications. The earliest symptoms may include colicky abdominal pain and constipation.…”

Section: Introductionmentioning

confidence: 99%

Effects of vincristine and monosodium glutamate on gastrointestinal motility and visceral sensitivity

López‐Tofiño,

de Sosa,

Vera

et al. 2023

Neurogastroenterology Motil

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BackgroundChemotherapy‐induced adverse effects are an unresolved nightmare. In preclinical studies in rats, the food additive monosodium glutamate (MSG) improved some of the side effects caused by cisplatin, but its effects in other models of chemotherapy‐treated animals are not well known. The aim of this study was to test if MSG may improve some of the adverse effects induced by vincristine in rats.MethodsYoung male Wistar rats were exposed or not to MSG (4 g L−1) in drinking water from week 0 till 1 week after treatment (week 3). Rats received two cycles of five daily intraperitoneal (ip) injections (Monday to Friday, weeks 1 and 2) of either saline (2 mL kg−1) or vincristine (0.1 mg kg−1). Gastrointestinal motility was measured in vivo by radiological methods after the first and tenth ip administrations. On week 3, the threshold for mechanical somatic and colorectal sensitivity was recorded using Von Frey filaments applied to the paws and an intracolonic balloon, respectively. Finally, samples of the terminal ileum and distal colon were histologically evaluated in sections.Key ResultsVincristine reduced body weight gain, food intake, and upper gastrointestinal transit, caused somatic (but not visceral) hypersensitivity and increased the thickness of the submucosal and muscle layers of the small intestine. In vincristine‐treated animals, MSG partially prevented gastrointestinal dysmotility and reduced visceral sensitivity but did not improve structural alterations of the small intestine.Conclusions & InferencesMSG could be used as an adjuvant to conventional treatments to improve some gastrointestinal dysfunctions caused by chemotherapy.

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Lactulose in Vincristine‐induced Constipation

Cited by 19 publications

References 7 publications

Involvement of Cannabinoid Signaling in Vincristine-Induced Gastrointestinal Dysmotility in the Rat

Involvement of Cannabinoid Signaling in Vincristine-Induced Gastrointestinal Dysmotility in the Rat

L-PROBe: A Novel Non-anthracycline Combination Chemotherapy Regimen for Aggressive B Cell Non-Hodgkin Lymphoma in Elderly Patients

Effects of vincristine and monosodium glutamate on gastrointestinal motility and visceral sensitivity

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