Endocrinology and Metabolism

Original Articles

Protective Effects of Inducible HO-1 on Oxygen Toxicity in Rat Brain Endothelial Microvessel Cells: Seung-Jun Yoo, Neal K. Nakra, Gabriele V. Ronnett, Cheil Moon; Endocrinol Metab. 2014;29(3):356-362. Published online September 25, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.3.356

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Background

Reperfusion in ischemia is believed to generate cytotoxic oxidative stress, which mediates reperfusion injury. These stress conditions can initiate lipid peroxidation and damage to proteins, as well as promote DNA strand breaks. As biliverdin and bilirubin produced by heme oxygenase isoform 1 (HO-1) have antioxidant properties, the production of both antioxidants by HO-1 may help increase the resistance of the ischemic brain to oxidative stress. In the present study, the survival effect of HO-1 was confirmed using hemin.

Methods

To confirm the roles of HO-1, carbon monoxide, and cyclic guanosine monophosphate further in the antioxidant effect of HO-1 and bilirubin, cells were treated with cycloheximide, desferoxamine, and zinc deuteroporphyrin IX 2,4 bis glycol, respectively.

Results

HO-1 itself acted as an antioxidant. Furthermore, iron, rather than carbon monoxide, was involved in the HO-1-mediated survival effect. HO-1 activity was also important in providing bilirubin as an antioxidant.

Conclusion

Our results suggested that HO-1 helped to increase the resistance of the ischemic brain to oxidative stress.

Citations

Citations to this article as recorded by

The Effects of Naringin on Cigarette Smoke-Induced Dynamic Changes in Oxidation/Antioxidant System in Lung of Mice
Pan Chen, Ziting Xiao, Hao Wu, Yonggang Wang, Weiwei Su, Peibo Li
Natural Product Communications.2020; 15(8): 1934578X2094723. CrossRef
Antioxidation Effect of Simvastatin in Aorta and Hippocampus: A Rabbit Model Fed High-Cholesterol Diet
Guangyin Zhang, Ming Li, Yinzhi Xu, Li Peng, Cui Yang, Yanan Zhou, Junping Zhang
Oxidative Medicine and Cellular Longevity.2016; 2016: 1. CrossRef
Vasculoprotective Effects of 3-Hydroxybenzaldehyde against VSMCs Proliferation and ECs Inflammation
Byung Soo Kong, Soo Jung Im, Yang Jong Lee, Yoon Hee Cho, Yu Ri Do, Jung Woo Byun, Cheol Ryong Ku, Eun Jig Lee, Maria Cristina Vinci
PLOS ONE.2016; 11(3): e0149394. CrossRef
Heme oxygenase-1-derived bilirubin protects endothelial cells against high glucose-induced damage
Meihua He, Mariapaola Nitti, Sabrina Piras, Anna Lisa Furfaro, Nicola Traverso, Maria Adelaide Pronzato, Giovanni E. Mann
Free Radical Biology and Medicine.2015; 89: 91. CrossRef
Articles in 'Endocrinology and Metabolism' in 2014
Won-Young Lee
Endocrinology and Metabolism.2015; 30(1): 47. CrossRef
Involvement of the Heme-Oxygenase Pathway in the Antiallodynic and Antihyperalgesic Activity of Harpagophytum procumbens in Rats
Carmela Parenti, Giuseppina Aricò, Santina Chiechio, Giulia Di Benedetto, Rosalba Parenti, Giovanna Scoto
Molecules.2015; 20(9): 16758. CrossRef

The Association between Low Serum Bilirubin and Carotid Atherosclerosis in Subjects with Type 2 Diabetes.: Byoung Hyun Park, Hye Jung Nho, Chung Gu Cho; Endocrinol Metab. 2012;27(2):126-131. Published online June 20, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.2.126

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Abstract PDF

BACKGROUND
Bilirubin prevents oxidative modification of low density lipoprotein, and may protect vessels from atherosclerosis. Several studies showed an inverse relationship between serum bilirubin and coronary artery disease. However, there are some needs to clarify the relationship between serum bilirubin and carotid atherosclerosis in type 2 diabetes, especially. METHODS: A total of 346 type 2 diabetic patients, between 35 and 95 years of age (146 men and 200 women), were studied. Subjects with normal serum total bilirubin were divided into two groups, according to their serum total bilirubin levels (group I, total bilirubin > or = 1.0 mg/dL [n = 59]; group II, total bilirubin < or = 0.5 mg/dL [n = 76]). Carotid intima-media thickness (IMT) and plaque scores were measured by ultrasonography. Carotid atherosclerosis was defined by the presence of plaque or more than 1 mm of common carotid IMT. RESULTS: Carotid IMT was positively correlated with age, duration of diabetes and hypertension, high sensitive C-reactive protein (hs-CRP) and fibrinogen, but, it was negatively correlated with bilirubin, gamma glutaryltransferase, albumin, hemoglobin, cystatin C and estimated-glomerular filtration rate (GFR) in all subjects. After controlling for sex, age and levels of hemoglobin, direct bilirubin only was negatively correlated with carotid IMT (r = -0.151, P = 0.034). Low serum total bilirubin group had a lot of female, long duration of diabetes and hypertension, higher hs-CRP, platelet counts, serum creatinine, HbA1c and homeostasis model assessment-insulin resistance, lower albumin, hemoglobin, estimated-GFR and quantitative insulin sensitivity check index. Carotid IMT and plaque scores were significantly greater in low serum bilirubin group (0.785 +/- 0.210 mm vs. 0.678 +/- 0.146 mm, P < 0.01; 1.95 +/- 2.56 vs. 1.03 +/- 1.40, P < 0.05, respectively) than in the high serum bilirubin group. Multivariate logistic regression analysis showed that age, serum albumin and total bilirubin were independent associated factors for carotid atherosclerosis in type 2 diabetic women. CONCLUSION: Total bilirubin is inversely correlated with carotid atherosclerosis in type 2 diabetic patients, and it is an independent associated factor for carotid atherosclerosis in women.

Citations

Citations to this article as recorded by

Circulating bilirubin and defense against kidney disease and cardiovascular mortality: mechanisms contributing to protection in clinical investigations
Ai-Ching Boon, Andrew C. Bulmer, Jeff S. Coombes, Robert G. Fassett
American Journal of Physiology-Renal Physiology.2014; 307(2): F123. CrossRef
Mildly Elevated Serum Bilirubin Levels Are Negatively Associated with Carotid Atherosclerosis among Elderly Persons
Ryuichi Kawamoto, Daisuke Ninomiya, Yoichi Hasegawa, Yoshihisa Kasai, Tomo Kusunoki, Nobuyuki Ohtsuka, Teru Kumagi, Masanori Abe, Jozef Dulak
PLoS ONE.2014; 9(12): e114281. CrossRef
Association between Total Bilirubin and Hemoglobin A1c in Korean Type 2 Diabetic Patients
Seong-Woo Choi, Young-Hoon Lee, Sun-Seog Kweon, Hye-rim Song, Hye-Ran Ahn, Jung-Ae Rhee, Jin-Su Choi, Min-Ho Shin
Journal of Korean Medical Science.2012; 27(10): 1196. CrossRef

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