From Cell Biology to Tissue Engineering


Therapeutic effects of an azaphenothiazine derivative in mouse experimental colitis

Jolanta Artym1, Maja Kocięba1, Ewa Zaczyńska1, Michał Zimecki1, Wojciech Kałas1, Leon Strządała1, Alicja Pawlak1, Małgorzata Jeleń2, Beata Morak-Młodawska2, Krystian Pluta2, Katarzyna Kaleta-Kuratewicz3, Jan P. Madej3, Piotr Kuropka3 and Jan Kuryszko3

1Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, 2Medical University of Silesia in Katowice, Faculty of Pharmaceutical Sciences in Sosnowiec, Department of Organic Chemistry and 3University of Environmental and Life Sciences, Division of Histology and Embryology, Wrocław, Poland

Offprint requests to: Michał Zimecki, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland. e-mail: michal.zimecki@hirszfeld.pl

Summary. Phenothiazines represent a class of compounds of potential therapeutic utility. In this report we evaluated therapeutic value of an azaphenothiazine derivative, 6-acetylaminobutyl-9-chloroquino[3,2-b]benzo[1,4]thiazine (QBT), given intragastrically, in the model of dextran sodium sulfate-induced colitis in C57BL/6 mice using 5-aminosalicylic acid (5-ASA) as a reference drug. Colitis symptoms such as body weight loss, diarrhea and hematochezia (blood in stool) were observed and registered and disease activity index (DAI) was calculated. In addition, weight and cell numbers in the lymphatic organs and histological parameters of the colon wall were analyzed. The effects of QBT on viability of colon epithelial cell lines were also determined. We showed that weight and cell number of draining mesenteric lymph nodes were lower in mice treated with QBT in comparison to their control counterparts. The number of thymocytes, drastically reduced in control mice, was elevated in mice treated with the compounds with a significant effect of 5-ASA. In addition, an abnormal composition of blood cell types was partially corrected in these groups. Histological analysis of the colon revealed that the pathological changes were partially normalized by QBT and even to a higher degree by 5-ASA. In conclusion we demonstrated a therapeutic efficacy of the compound in amelioration of local and systemic pathological changes associated with chemically-induced colitis in mice. A possible mechanism of action of the compound is discussed. Histol Histopathol 35, 691-699 (2020)

Key words: Azaphenothiazines, 5-ASA, Colitis, Dextran sodium sulfate, Mice

DOI: 10.14670/HH-18-192