Liraglutide and denatonium benzoate attenuate T2DM-induced metabolic, neurological, and testicular changes in rats: Targeting oxidative stress, inflammation, and BCRP transporter
Sahar A. Harby, Mona Hassan Fathelbab, Basma M. Nawwar, Eman Sheta, Dalia Ibrahim Halwag, Dalia Abd Elmoaty Elneily, Esraa S. Habiba
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引用次数: 0
Abstract
Type 2 diabetes mellitus (T2DM) adversely affects various organs, including the brain and its blood barrier. In addition to the brain, hyperglycemia damages the testes. The testes possess blood-tissue barriers that share common characteristics and proteins with the blood-brain barrier (BBB), including breast cancer-resistant protein (BCRP). This study aimed to investigate the impact of uncontrolled DM on the brain and testes, with a specific focus on BCRP. Moreover, it examined the effects of liraglutide (Lira) and denatonium benzoate (DB), a bitter taste receptor agonist, on T2DM. Forty adult male rats were randomized into five groups: normal control, diabetic, diabetic + DB, diabetic + Lira, and diabetic + DB + Lira. T2DM was induced using fructose and streptozotocin (STZ). After eight weeks of treatment, rats were sacrificed, and samples of blood, semen, testes, and brain were collected to evaluate metabolic and semen parameters, oxidative stress, inflammatory markers, histological features of the brain and testes, and BCRP expression. DB and Lira, both individually and in combination, mitigated fructose/STZ-induced hyperglycemia and dyslipidemia. Additionally, they enhanced SOD activity and reduced MDA, TNFα, and IL-6 levels in the brain and testes, alongside improving sperm quality and serum levels of FSH, LH, and testosterone. Rats treated with DB, Lira, or DB + Lira demonstrated improved brain and testicular tissue architecture. BCRP expression was upregulated in the brains and testes of Lira- and DB + Lira-treated rats. These findings indicated that DB positively affects the metabolic profile of T2DM. Furthermore, Lira and DB provided protection against T2DM-induced brain and testicular damage.
期刊介绍：
The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes.
Major research themes of particular interest include:
- Cell-Cell and Cell-Matrix Interactions;
- Connective Tissues;
- Development and Disease;
- Neuroscience.
Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance.
The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.
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