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Abstract Title:

Luteolin prevents irinotecan-induced intestinal mucositis in mice through antioxidant and anti-inflammatory properties.

Abstract Source:

Br J Pharmacol. 2020 Jan 24. Epub 2020 Jan 24. PMID: 31976547

Abstract Author(s):

Thaise Boeing, Priscila de Souza, Silvia Speca, Lincon Bordignon Somensi, Luisa Nathália Bolda Mariano, Benhur Judah Cury, Mariana Ferreira Dos Anjos, Nara Lins Meira Quintão, Laurent Dubuqoy, Pierre Desreumaux, Luisa Mota da Silva, Sérgio Faloni de Andrade

Article Affiliation:

Thaise Boeing

Abstract:

BACKGROUND AND PURPOSE: Intestinal mucositis refers to mucosal damage caused by cancer treatment and irinotecan is one of the agents most associated with this condition. Focusing on the development of alternatives to prevent this important adverse effect, we evaluated the activity of the flavonoid luteolin, which has never been tested for this purpose despite its biological potential.

EXPERIMENTAL APPROACH: The effects of luteolin were examined on irinotecan-induced intestinal mucositis in mice. Clinical signs were evaluated. Moreover, histological, oxidative and inflammatory parameters were analyzed, as well as the possible interference of luteolin in the antitumor activity of irinotecan.

KEY RESULTS: Luteolin at 30 mg/kg (p.o. or i.p), prevents irinotecan-induced intestinal damage by reducing weight loss and diarrhea score and attenuating the shortening of the duodenum and colon. The histological analysis confirmed that luteolin (30 mg/kg, p.o.) prevented villous shortening, vacuolization, and apoptosis of cells and preserved mucin production in the duodenum and colon. Moreover, luteolin treatment mitigated irinotecan-induced oxidative stress (i.e. by reducing the levels of ROS and LOOH, and augmenting endogenous antioxidants) and inflammation (i.e. through the decrease of MPO enzyme activity, TNF, IL-1β, and IL-6 levels; and increasing IL-4 and IL-10). Besides, the disruption of the tight junctions ZO-1 and occludin were also prevented by luteolin treatment. Importantly, luteolin did not interfere with the antitumor activity of irinotecan.

CONCLUSION AND IMPLICATIONS: Luteolin prevents intestinal mucositis induced by irinotecan and therefore could be a potential adjunct in antitumor therapy to control this adverse effect, increasing treatment adherence and consequently the chances of cancer remission.

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