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Protective and Curative Effects of Unconjugated Bilirubin on Gene Expression of Lox-1 and Inos in the Heart of Rats Receiving High-Fat Diet and Low Dose Streptozotocin: A Histomorphometric Approach Publisher



Maleki MH1, 3 ; Vakili O2 ; Tavakoli R1, 4 ; Nadimi E5 ; Noori Z6 ; Taghizadeh M1 ; Dehghanian A7, 8 ; Tayebi L9 ; Shafiee SM2
Authors
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Authors Affiliations
  1. 1. Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  2. 2. Autophagy Research Center, Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  3. 3. Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  5. 5. Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  6. 6. Department of Anatomical Sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  7. 7. Trauma Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  8. 8. Molecular Pathology and Cytogenetics Division, Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
  9. 9. Marquette University School of Dentistry, Milwaukee, 53233, WI, United States

Source: Journal of Inflammation (United Kingdom) Published:2024


Abstract

Background: Atherosclerosis is a chronic inflammatory condition affecting the large arteries and is a major cause of cardiovascular diseases (CVDs) globally. Increased levels of adhesion molecules in cardiac tissue serve as prognostic markers for coronary artery occlusion risk. Given the antioxidant properties of bilirubin and its inverse correlation with atherosclerosis, this study aimed to assess the beneficial effects of bilirubin on atherosclerotic indices and heart structure in high-fat diet-fed diabetic rats with atherosclerosis. Methods: Atherosclerosis was induced in three out of five groups of adult male Sprague Dawley rats through a 14-week period of high-fat diet (HFD) consumption and a single low dose of streptozotocin (STZ) (35 mg/kg). The atherosclerotic rats were then treated with intraperitoneal administration of 10 mg/kg/day bilirubin for either 6 or 14 weeks (treated and protected groups, respectively), or the vehicle. Two additional groups served as the control and bilirubin-treated rats. Subsequently, the mRNA expression levels of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), lectin-like LDL receptor 1 (LOX-1), and the inducible nitric oxide synthase (iNOS) were analyzed using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Histopathological and stereological analyses were performed to assess changes in the heart structure. Results: Bilirubin significantly decreased the expression of VCAM-1, ICAM-1, LOX-1, and iNOS genes in the treated group. Moreover, bilirubin mitigated pathological damage in the left ventricle of the heart. Stereological analysis revealed a decrease in the left ventricle and myocardium volume, accompanied by an increase in vessel volume in rats treated with bilirubin. Conclusion: These findings demonstrate that mild hyperbilirubinemia can protect against the progression of atherosclerosis and heart failure by improving lipid profile, modulating adhesion molecules, LOX-1, and iNOS gene expression levels. © The Author(s) 2024.
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