Abstract
Research into the accumulation patterns of protein oxidative modification (POM) products and lipids in Crohn’s disease (CD) and ulcerative colitis (UC) could have important implications for understanding the pathogenesis and improving the diagnosis and therapy for these diseases. The aim of this study was to investigate the aspects of free radical oxidation (FRO) in the large bowel and their possible correlations with clinical symptoms of UC and CD. In the Wistar rat model used in the experiment, CD was induced with 2,4,6-trinitrobenzenesulfonic acid, and UC was induced with oxazolone. Clinical status was assessed using the Disease activity index (DAI). Lipid peroxidation (LPO) products were measured in the heptane and isopropanol phases of the intestinal mucosa extract. POM products were measured following spontaneous and stimulated oxidation. The DAI ( Me (Q25–Q75)) was increased in both CD and UC on days 3 and 7 of the experiment: for CD, it was equally increased on days 3 and 7 (7 (3-7)) and was 11 (11–11) and 11 (9–11) for UC on days 3 and 7, respectively. The amount of primary, secondary and end LPO products in the heptane and isopropanol phases, as well as the total amount of POM products, was increased in the homogenized mucosa of the large bowel. In the CD group, the relative content of secondary basic POM products was increased on day 7 of the experiment. The following patterns of FRO were revealed: accumulation of LPO products in the UC group and accumulation of POM products in the CD group; UC is characterized by the accumulation of mostly LPO products in the heptane phase and secondary LPO products in the isopropanol phase; CD is characterized by the accumulation of secondary basic POM products. DAI scores were correlated with the amount of LPO products in the isopropanol phase and the amount of POM products in the spontaneous oxidation mode. The highest number of strong correlations was observed in the UC group. Our findings suggest a very serious contribution of FRO changes to the pathogenesis of UC and CD, meaning that LPO and POM products could be regarded as diagnostic markers and indicators of treatment efficacy.
Highlights
Research into the accumulation patterns of protein oxidative modification (POM) products and lipids in Crohn’s disease (CD) and ulcerative colitis (UC) could have important implications for understanding the pathogenesis and improving the diagnosis and therapy for these diseases
We found that on days 3 and 7 of trinitrobenzenesulfonic acid (TNBS)-induced CD and oxazolone-induced UC, Disease activity index (DAI) scores, the amount of primary, secondary and end Lipid peroxidation (LPO) products in the heptane and isopropanol phases of homogenized intestinal mucosa and the total amount of POM products were increased
In the setting of UC, free radical oxidation (FRO) was characterized by the accumulation of mostly LPO products, in contrast to CD characterized by the accumulation of mostly POM products
Summary
Research into the accumulation patterns of protein oxidative modification (POM) products and lipids in Crohn’s disease (CD) and ulcerative colitis (UC) could have important implications for understanding the pathogenesis and improving the diagnosis and therapy for these diseases. The aim of this study was to investigate the aspects of free radical oxidation (FRO) in the large bowel and their possible correlations with clinical symptoms of UC and CD. ROS and RNS, as well as products of their interaction with proteins and lipids, can act as markers of intestinal tissue damage, indicating the severity of the disease and the efficacy of treatment; they are potential targets for novel personalized therapeutic and preventive approaches to the regulation of the local redox state in the large bowel affected by CD and UC [11,12,13]. It would be interesting to study the aspects of free radical oxidation (FRO) and the relationship between the redox state of the intestinal lesion and the severity of clinical manifestations in UC and CD. In our in vivo experiment described below, we aimed to investigate the aspects of FRO in the large intestine and the relationship between FRO and the clinical manifestations of UC and CD
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