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.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.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.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.
