Irinotecan chemotherapy-induced intestinal oxidative stress: Underlying causes of disturbed mucosal water and electrolyte transport

Rtibi, Kaïs; Selmi, Slimen; Grami, Dhekra; Sebaï, Hichem; Amri, Mohamed; Marzouki, Lamjed

doi:10.1016/j.pathophys.2017.07.002

Cited by 30 publications

(21 citation statements)

References 26 publications

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“…They suggested that the oxidative stress was the main mechanism of irinotecan-induced mucosal toxicity. 36 Additionally, the present study could demonstrate signs of inflammation in the form of dilated congested blood vessels and mild mononuclear cellular infiltration. This could suggest that inflammation is involved in irinotecan-induced tongue mucosal toxicity.…”

Section: Discussionsupporting

confidence: 51%

“…In addition, a more recent study showed that irinotecan administration in rats led to an intestinal mucosal damage that was manifested by disorganized epithelial architecture, epithelial damage, atrophy of the villi and inflammatory cellular infiltration. They suggested that the oxidative stress was the main mechanism of irinotecan‐induced mucosal toxicity …”

Section: Discussionmentioning

confidence: 99%

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Effect of irinotecan on the tongue mucosa of juvenile male albino rat at adulthood

Ibrahim

Elwan

2019

Int J Experimental Path

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Summary Irinotecan is one of the most important anti‐tumour drugs against a broad spectrum of malignancies, but is known to be associated with possible oral complications. The aim of the present study was to evaluate the effect of irinotecan on the tongue mucosa of juvenile male albino rat at adulthood using different histological and immunohistochemical methods. Twenty juvenile male albino rats were divided equally into two groups: control and irinotecan‐treated group (single injection of 200 mg irinotecan/kg, then kept for four weeks without treatment). The tongue specimens were processed for light microscopy and scanning electron microscopy. The irinotecan‐treated group showed statistically significant shortening and thinning of the lingual papillae. There was loss of the normal appearance of the filiform papillae with focal cell loss alternating with areas of hyperkeratosis. Focal separation of the keratin layer, some nuclear changes and vacuolation of some epithelial cells were detected. Dilated congested blood vessels and mild mononuclear cellular infiltration were encountered. Atrophic fungiform papillae with ill‐defined taste bud cells were observed. A statistically significant decrease in the pattern of Ki67 immunohistochemical staining reaction was detected in comparision to the control group. Scanning electron microscopy revealed different signs of atrophy of the tongue papillae. Focal areas of desquamation of lingual papillae were observed revealing some filiform papillae with desquamated surface, bisected tips and evident thinning. Some extravasated red blood cells could be detected. Thus irinotecan caused significant morphological and morphometrical alterations of the tongue mucosa in particularly the filiform papillae.

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Effect of irinotecan on the tongue mucosa of juvenile male albino rat at adulthood

Ibrahim

Elwan

2019

Int J Experimental Path

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“…[ 46 ] to 300 mg/kg [ 47 ]. Most representative toxicity studies with IRI conducted on rats [ 47 , 48 , 49 , 50 , 51 ] evaluated the effects of a single dose of 200 mg/kg, which has low mortality, but caused reproducible gastrointestinal mucositis.…”

Section: Resultsmentioning

confidence: 99%

Irinotecan and Δ9-Tetrahydrocannabinol Interactions in Rat Liver: A Preliminary Evaluation Using Biochemical and Genotoxicity Markers

et al. 2018

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There is growing interest regarding the use of herbal preparations based on Cannabis sativa for medicinal purposes, despite the poorly understood interactions of their main constituent Δ9-tetrahydrocannabinol (THC) with conventional drugs, especially cytostatics. The objective of this pilot study was to prove whether the concomitant intake of THC impaired liver function in male Wistar rats treated with the anticancer drug irinotecan (IRI), and evaluate the toxic effects associated with this exposure. IRI was administered once intraperitoneally (at 100 mg/kg of the body weight (b.w.)), while THC was administered per os repeatedly for 1, 3, and 7 days (at 7 mg/kg b.w.). Functional liver impairments were studied using biochemical markers of liver function (aspartate aminotransferase—AST, alanine aminotransferase—ALP, alkaline phosphatase—AP, and bilirubin) in rats given a combined treatment, single IRI, single THC, and control groups. Using common oxidative stress biomarkers, along with measurement of primary DNA damage in hepatocytes, the degree of impairments caused at the cellular level was also evaluated. THC caused a time-dependent enhancement of acute toxicity in IRI-treated rats, which was confirmed by body and liver weight reduction. Although single THC affected ALP and AP levels more than single IRI, the levels of liver function markers measured after the administration of a combined treatment mostly did not significantly differ from control. Combined exposure led to increased oxidative stress responses in 3- and 7-day treatments, compared to single IRI. Single IRI caused the highest DNA damage at all timepoints. Continuous 7-day oral exposure to single THC caused an increased mean value of comet tail length compared to its shorter treatments. Concomitant intake of THC slightly affected the levels of IRI genotoxicity at all timepoints, but not in a consistent manner. Further studies are needed to prove our preliminary observations, clarify the underlying mechanisms behind IRI and THC interactions, and unambiguously confirm or reject the assumptions made herein.

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“…The improvement in clinical signals and intestinal injury after FRF‐BF treatment was associated with improvement in the availability of the GSH, a crucial endogen antioxidant in the cellular defense against oxidative stress (Nemmiche, ). The oxidative stress has been demonstrated to exert a fundamental role in mucositis induced by irinotecan (Rtibi et al, ) and the production of reactive oxygen species (ROS) from enterocytes exposed to chemotherapy corroborates in this process (Arifa et al, ). Several studies have demonstrated that flavonoids act favoring the antioxidant defenses (Goya et al, ; Pérez‐Cano & Castell, ).…”

Section: Discussionmentioning

confidence: 99%

Flavonoid‐rich fraction of Bauhinia forficata Link leaves prevents the intestinal toxic effects of irinotecan chemotherapy in IEC‐6 cells and in mice

Cechinel-Zanchett

Boeing

Somensi

et al. 2018

Phytotherapy Research

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This study evaluated the effects of flavonoid-rich fraction from Bauhinia forficata leaves (FRF-BF), against intestinal toxicity induced by irinotecan. The leaves of this plant are used like tea in Brazilian folk medicine, and it is rich in flavonoids, mainly kaempferitrin.First, the chemopreventive effects of FRF-BF and kaempferitrin were evaluated in intestinal cells (IEC-6 cells) exposed to irinotecan. Next, the effects were evaluated against irinotecan-induced mucositis in mice. Lastly, melanoma was induced in C57BL/6 mice to evaluate FRF-BF interference on irinotecan antitumor activity. The results showed that FRF-BF and kaempferitrin exert no cytotoxic effects in IEC-6 cells and confirmed that pretreatment with FRF-BF and kaempferitrin displays chemoprotective effects against cytotoxicity induced by irinotecan. Interestingly, the FRF-BF (100 mg/kg, p.o) reduced the intestinal motility in mice and attenuated parameters linked to irinotecaninduced intestinal mucositis, including diarrhea, histological damage, depletion of duodenal GSH, amount of TNF-α, and MPO activity in the small intestine. Also, FRF-BF does not interfere in the antitumor activity of irinotecan and exerted antitumoral activity in murine melanoma. In conclusion, FRF-BF (100 mg/kg, p.o) presents promising pharmacological potential to prevent and attenuate the severity of intestinal mucositis during chemotherapy treatment, related to the presence of kaempferitrin.

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Irinotecan chemotherapy-induced intestinal oxidative stress: Underlying causes of disturbed mucosal water and electrolyte transport

Cited by 30 publications

References 26 publications

Effect of irinotecan on the tongue mucosa of juvenile male albino rat at adulthood

Effect of irinotecan on the tongue mucosa of juvenile male albino rat at adulthood

Irinotecan and Δ9-Tetrahydrocannabinol Interactions in Rat Liver: A Preliminary Evaluation Using Biochemical and Genotoxicity Markers

Flavonoid‐rich fraction of Bauhinia forficata Link leaves prevents the intestinal toxic effects of irinotecan chemotherapy in IEC‐6 cells and in mice

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