Abnormal Homeostasis in the Redox State and Related Signaling Pathways, in Irritable Bowel Syndrome

Abstract

Background: IBS is multifactorial; however, elucidating its underlying mechanisms is crucial for advancing in its diagnosis and management. Aims: Evaluate molecular processes related to oxidative stress (OS) and inflammation in IBS and its subtypes. Methods: Thirty Rome III-IBS outpatients and 30 controls were studied for OS biomarkers, including malondialdehyde (MDA), protein carbonyls (PC), reduced glutathione (GSH), and oxidized glutathione (GSSG). Also, serum interleukins (IL-10, IL-4, TNF-α, IL-6), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), and nicotinamide-adenine-dinucleotide phosphate (NADPH) catalytic subunit gp91phox. Results: In IBS vs. controls there were higher MDA: 4.44 ± 1.76 vs. 2.42 ± 0.5 nmol/mg/protein (p < 0.01); GSSG: 57.17 ± 17.49 vs. 42.73 ± 14.26 μM (p < 0.01); and lower GSH: 26.17 ± 12.36 vs. 38.47 ± 16.71 μM (p < 0.01). Also, an imbalance in pro- and anti-inflammatory interleukins (p < 0.01); and higher NF-κB: 5.33 ± 3.39 vs. 3.08 ± 1.19 (p = 0.01); gp91phox: 4.28 ± 1.81 vs. 3.29 ± 1.03 (p < 0.05); and lower Nrf2: 3.87 ± 2.9 vs. 7.56 ± 2.59 (p < 0.05). Additionally, there were no significant differences between the IBS subtypes, nor according to severity. Finally, in IBS-C, MDA correlated with IL-4, TNF-α with IL-10; and in IBS-D, GSH correlated with IL-4 and no differences in transcription factors. Conclusions: The data demonstrate an alteration in the homeostasis of the cellular redox state in IBS. Also, in IBS-D, the antioxidant effect counteracts the low-grade inflammation, whereas in IBS-C, it is mainly driven by interleukins.