Effects of the food additive monosodium glutamate on cisplatin‐induced gastrointestinal dysmotility and peripheral neuropathy in the rat

Abstract

Background: Cisplatin is an antineoplastic drug known to produce intense vomiting, gastric dysmotility, and peripheral neuropathy. Monosodium glutamate (MSG) is a flavor enhancer with prokinetic properties potentially useful for cancer patients under chemotherapy. Our aim was to test whether MSG may improve gastrointestinal motor dysfunction and other adverse effects induced by repeated cisplatin in rats. Methods: Male Wistar rats were exposed or not to MSG (4 g L −1) in drinking water from week 0 to 1 week after treatment. On the first day of weeks 1-5, rats were treated with saline or cisplatin (2 mg kg −1 week −1 , ip). Gastrointestinal motility was measured by radiological methods after first and fifth administrations, as well as 1 week after treatment finalization. One week after treatment, the threshold for mechanical somatic sensitivity was recorded. Finally, samples of stomach, terminal ileum and kidneys were evaluated in sections using conventional histology. The myenteric plexus was immunohistochemically evaluated on distal colon whole-mount preparations. Key Results: Monosodium glutamate prevented the development of cisplatin-induced neuropathy and partially improved intestinal transit after the fifth cisplatin administration with little impact on gastric dysmotility. MSG did not improve the histological damage of gut wall, but prevented the changes induced by cisplatin in the colonic myenteric plexus. Conclusion and Inferences: Our results suggest that MSG can improve some dysfunctions caused by anticancer chemotherapy in the gut and other systems, associated, at least partially, with neuroprotectant effects. The potentially useful adjuvant role of this food additive to reduce chemotherapy-induced sequelae warrants further evaluation.

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

“…4 MSG, alone or combined with vincristine, did not modify body weight or food and liquid intake, in agreement with previous results in control rats 21 or rats treated with another antineoplastic drug, cisplatin. 19 Chronic vincristine administration induced mechanical allodynia (a sign of peripheral neuropathy) when the Von Frey test was applied 1 week after treatment finalization, also in agreement with previous reports. 4,30,31 In this study, MSG could not prevent the development of neuropathic pain caused by vincristine.…”

“…Mechanical sensitivity was assessed in cohort 2 by measuring the withdrawal threshold to calibrate Von Frey hairs (2-60 g; Bioseb Instruments, USA) after treatment finalization, on week 3 (as previously described 4,19 ). Rats were placed individually on an elevated iron mesh in a clear plastic cage and allowed to adapt to the testing environment for at least 10 min 2-3 days before the assessment.…”

Radiographic assessment of the impact of sex and the circadian rhythm-dependent behaviour on gastrointestinal transit in the rat

“…As expected, in this study the transit pattern in M-N group was similar to that previously found by other authors and also by our group. 12,17–19…”

“…As expected, in this study the transit pattern in M-N group was similar to that previously found by other authors and also by our group. 12,[17][18][19] The present study benefits from the performing of a comprehensive analysis of the faecal pellets collected during the radiographic session. The percentage of stained faecal pellets showed a progressive increase from T4 to T24.…”

Based on network pharmacology and molecular docking to explore the protective effect of Epimedii Folium extract on cisplatin-induced intestinal injury in mice

“…Cisplatin is a broad-spectrum and highly effective platinum-based antitumor drug, which is widely used in the treatment of various solid tumors such as lung cancer ( Wang et al, 2021 ), gastric cancer, breast cancer ( Vidra et al, 2022 ), ovarian cancer ( Muhanmode et al, 2021 ), and bladder cancer. However, the dose-limiting toxicities of cisplatin, such as nephrotoxicity ( Ma et al, 2021 ), ototoxicity ( Tserga et al, 2020 ), neurotoxicity, hepatotoxicity ( Abd Rashid et al, 2021 ), cardiotoxicity ( Xu et al, 2021 ), and gastrointestinal toxicity ( Lopez-Tofino et al, 2021 ), severely limit its application in clinical oncology. Among them, gastrointestinal toxicity is the most essential clinical dose-limiting side effect, which dramatically affects the antitumor efficacy of cisplatin, seriously affects the quality of life of patients, and even needs to stop chemotherapy ( Blijlevens et al, 2000 ).…”