ArticleClinical and experimental immunology2010
Beneficial effects of cathepsin inhibition to prevent chemotherapy-induced intestinal mucositis.
Article in Clinical and experimental immunology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- High-intensity intermittent training ameliorates methotrexate-induced acute lung injury.BMC pulmonary medicine · 2024Article
- Cynaroside ameliorates methotrexate-induced enteritis in rats through inhibiting NLRP3 inflammasome activation.Frontiers in immunology · 2024Article
- Experimental Chemotherapy-Induced Mucositis: A Scoping Review Guiding the Design of Suitable Preclinical Models.International journal of molecular sciences · 2022Article
- Protective Impacts ofEvidence-based complementary and alternative medicine : eCAM · 2020Article
- Effect of lutein on methotrexate-induced oxidative lung damage in rats: a biochemical and histopathological assessment.The Korean journal of internal medicine · 2019Article
- Beneficial role of virgin coconut oil supplementation against acute methotrexate chemotherapy-induced oxidative toxicity and inflammation in rats.Integrative medicine research · 2018Article
- Effect ofClinical and experimental otorhinolaryngology · 2017Article
- Effects of nimesulide on the small intestine mucositis induced by methotrexate in rats.Experimental animals · 2016Article
- The Impact of Resveratrol on Oxidative Stress Induced by Methotrexate in Rat Ileum Tissue: Evaluation of Biochemical and Histopathological Features and Analysis of Gene Expression.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2016Article
- Increased Ghrelin but Low Ghrelin-Reactive Immunoglobulins in a Rat Model of Methotrexate Chemotherapy-Induced Anorexia.Frontiers in nutrition · 2016Article
- Cysteine cathepsin proteases: regulators of cancer progression and therapeutic response.Nature reviews. Cancer · 2015Review
- Novel Manganese-Porphyrin Superoxide Dismutase-Mimetic Widens the Therapeutic Margin in a Preclinical Head and Neck Cancer Model.International journal of radiation oncology, biology, physics · 2015Article
- The effect of hippophae rhamnoides extract on oral mucositis induced in rats with methotrexate.Journal of applied oral science : revista FOBArticle
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6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
One of the main secondary toxic side effects of anti-mitotic agents used to treat cancer patients is intestinal mucositis. Previous data showed that cathepsin D activity, contributing to the proteolytic lysosomal pathway, is up-regulated during intestinal mucositis in rats. At the same time, cathepsin inhibition limits intestinal damage in animal models of inflammatory bowel diseases. The aim of this study was to evaluate the effects of cathepsin inhibition on methotrexate-induced mucositis in rats. Male Sprague-Dawley rats received saline solution subcutaneously as the control group or 2·5 mg/kg of methotrexate for 3 days (D0-D2). From D0 to D3 methotrexate-treated rats also received intraperitoneal injections of pepstatin A, a specific inhibitor of cathepsin D or E64, an inhibitor of cathepsins B, H and L, or vehicle. Rats were euthanized at D4 and jejunal samples were collected. Body weight and food intake were partially preserved in rats receiving E64 compared with rats receiving vehicle or pepstatin A. Cathepsin D activity, used as a marker of lysosomal pathway, was reduced both in E64 and pepstatin-treated rats. However, villus atrophy and intestinal damage observed in methotrexate-treated rats were restored in rats receiving E64 but not in rats receiving pepstatin A. The intramucosal concentration of proinflammatory cytokines, interleukin-1β and cytokine-induced neutrophil chemoattractant (CINC)-2, was markedly increased in methotrexate-treated rats receiving vehicle or pepstatin A but not after E64 treatment. In conclusion, a large broad inhibition of cathepsins could represent a new potential target to limit the severity of chemotherapy-induced mucositis as opposed to the inhibition of cathepsin D alone.
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