Unconjugated Bilirubin Attenuates DSS-Induced Colitis Potentially via Enhancement of Bilirubin Reabsorption

Zhao, Chong; Huang, Honglan; Pan, Qiuhua; Huang, Wenqi; Wu, Ping; Xu, Haoming; Feng, Zhiqiang; Du, Yanlei; Nie, Yuqiang; Zhou, Yongjian

doi:10.3389/fphar.2021.654808

Cited by 8 publications

(6 citation statements)

References 43 publications

(48 reference statements)

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“…IBIL is a powerful antioxidant, and the work by Zhao et al [23] demonstrated that IBIL can directly scavenge superoxide anion radicals at the sites of inflammation. Furthermore, in a mouse model of autoimmune arthritis, exogenous IBIL injections significantly reduced oxidative DNA damage, neutrophil infiltration, and fibrin deposition in the joint cavity, leading to a decrease in inflammation and alleviating the symptoms of joint damage [24].…”

Section: Discussionmentioning

confidence: 99%

Gamma-glutamyl transpeptidase and indirect bilirubin may participate in systemic inflammation of patients with psoriatic arthritis

Wang,

Mao,

et al. 2023

Adv Rheumatol

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Background Previous studies have suggested that systemic metabolic abnormalities are closely related to psoriatic arthritis (PsA). Gamma-glutamyl transpeptidase (GGT) and indirect bilirubin (IBIL), two essential active substances in hepatic metabolism that have been demonstrated as an oxidative and anti-oxidative factor respectively, have been proved to be involved in oxidative stress damage and inflammation in several human diseases. However, their role in PsA remains unclear. Methods In this retrospective comparative cohort study, a case group of 68 PsA patients and a control group of 73 healthy volunteers from the Third Hospital of Hebei Medical University were enrolled. Serum GGT, IBIL, GGT/IBIL ratio and C-reactive protein (CRP), a well applied bio-marker of systemic inflammatory in PsA, were compared between the two groups. Furthermore, the relationship of GGT, IBIL and GGT/IBIL with CRP were explored in PsA patients. Finally, the patients were divided into high inflammation group and low inflammation group according to the median value of CRP. Multivariate logistic regression analyses were used for the association of systemic inflammation level with GGT, IBIL and GGT/IBIL. Results Compared with healthy controls, PsA patients exhibited significantly higher serum GGT, GGT/IBIL, and CRP levels and lower IBIL levels. Serum GGT and GGT/IBIL were positively correlated with CRP, whereas IBIL were negatively correlated with CRP. Binary logistic regression analysis revealed that serum GGT was a risk factor for high CRP in PsA, whereas IBIL was a protective factor. Furthermore, GGT/IBIL was a better indicator of high CRP condition in PsA patients than either GGT or IBIL alone, as determined by the receiver operating characteristic curves. Conclusion GGT and IBIL may participate in the pathogenesis of PsA. Additionally, GGT, IBIL and the balance of the two may reflect systemic inflammation mediated by oxidative stress events related to metabolic abnormalities to a certain extent.

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Section: Discussionmentioning

confidence: 99%

Gamma-glutamyl transpeptidase and indirect bilirubin may participate in systemic inflammation of patients with psoriatic arthritis

Wang,

Mao,

et al. 2023

Adv Rheumatol

View full text Add to dashboard Cite

show abstract

“…IBIL is a powerful antioxidant, and the work by Zhao et al [23] demonstrated that IBIL can directly scavenge superoxide anion radicals at the sites of in ammation. Furthermore, in a mouse model of autoimmune arthritis, exogenous IBIL injections signi cantly reduced oxidative DNA damage, neutrophil in ltration, and brin deposition in the joint cavity, leading to a decrease in in ammation and alleviating the symptoms of joint damage [24].…”

Section: Discussionmentioning

confidence: 99%

Gamma-glutamyl transpeptidase and indirect bilirubin may participate in systemic inflammation of patients with psoriatic arthritis

Wang

Mao

Shang

et al. 2023

Preprint

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Background: Previous studies have suggested that systemic metabolic abnormalities are closely related to Psoriatic arthritis (PsA). Gamma-glutamyl transpeptidase (GGT) and indirect bilirubin (IBIL), two essential active substances in hepatic metabolism that have been demonstrated as an oxidative and anti-oxidative factor respectively, have been proved to be involved in oxidative stress damage and inflammation in several human diseases. However, their role in PsA remains unclear. Methods: In this retrospective comparative cohort study, a case group of 68 PsA patients and a control group of 73 healthy volunteers from the Third Hospital of Hebei Medical University were enrolled. Serum GGT, IBIL, GGT/IBIL ratio and C-reactive protein (CRP), a well applied bio-marker of systemic inflammatory in PsA, were compared between the two groups. Furthermore, the relationship of GGT, IBIL and GGT/IBIL with CRP were explored in PsA patients. Finally, the patients were divided into high inflammation group and low inflammation group according to the median value of CRP. Multivariate logistic regression analyses were used for the association of systemic inflammation level with GGT, IBIL and GGT/IBIL. Results: Compared with healthy controls, PsA patients exhibited significantly higher serum GGT, GGT/IBIL, and CRP levels and lower IBIL levels. Serum GGT and GGT/IBIL were positively correlated with CRP, whereas IBIL were negatively correlated with CRP. Binary logistic regression analysis revealed that serum GGT was a risk factor for high CRP in PsA, whereas IBIL was a protective factor. Furthermore, GGT/IBIL was a better indicator of high CRP condition in PsA patients than either GGT or IBIL alone, as determined by the receiver operating characteristic curves. Conclusion: GGT and IBIL may participate in the pathogenesis of PsA. Additionally, GGT, IBIL and the balance of the two may reflect systemic inflammation mediated by oxidative stress events related to metabolic abnormalities to a certain extent.

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“…Recent investigations have demonstrated a variety of biological properties of this the metabolite of iron porphyrin at physiological concentrations, such as anti-oxidative and antiinflammatory (39,40). In animal models of experimental colitis, BIL protects mice from DSS-induced colitis, possibly via reducing mucosal leukocyte infiltration, maintaining redox homeostasis (41), and promoting BIL reabsorption via enterohepatic cycling (42). With regard to human IBD, patients with the Gilbert's polymorphism have a decreased risk of CD (43) and patients with IBD show significantly lower levels of BIL than controls (20).…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Novel Neutrophil-Based Biomarkers in the Diagnosis and Prediction of Response to Infliximab Therapy in Crohn’s Disease

et al. 2022

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With the increasing incidence and prevalence, Crohn’s disease (CD) has become one of the most challenging diseases in both diagnosis and treatment of gastroenterology. Evaluation of the disease activity and mucosal healing guides clinical decisions regarding subsequent therapy for CD. In this study, we enrolled a total of 144 patients with CD and 239 healthy controls were enrolled. Clinical characteristics and laboratory parameters of enrolled subjects were retrieved from the electronic medical record database of our hospital. Serum cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). Mucosa expression levels of inflammatory agents were measured by quantitative RT-PCR (qRT-PCR). We identified two neutrophil-based indexes, the neutrophil-to-albumin ratio (NAR) and neutrophil-to-bilirubin ratio (NBR), both of which had not yet been explored in CD or UC. NAR and NBR were significantly increased in patients with CD compared to those in healthy controls, and both indexes showed significantly positive correlations with CD activity and inflammatory load. In note, NAR and NBR showed better performance than blood neutrophil percentage, serum albumin, or bilirubin alone in these scenarios. More importantly, both NAR and NBR discriminated CD patients who completely or partially responded to infliximab (IFX) induction therapy from those with primary non-response. Our observations suggest that NAR and NBR may serve as promising biomarkers in the diagnosis and prediction of response to IFX therapy in CD.

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Unconjugated Bilirubin Attenuates DSS-Induced Colitis Potentially via Enhancement of Bilirubin Reabsorption

Cited by 8 publications

References 43 publications

Gamma-glutamyl transpeptidase and indirect bilirubin may participate in systemic inflammation of patients with psoriatic arthritis

Gamma-glutamyl transpeptidase and indirect bilirubin may participate in systemic inflammation of patients with psoriatic arthritis

Gamma-glutamyl transpeptidase and indirect bilirubin may participate in systemic inflammation of patients with psoriatic arthritis

Clinical Significance of Novel Neutrophil-Based Biomarkers in the Diagnosis and Prediction of Response to Infliximab Therapy in Crohn’s Disease

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