Sarker Manoneeta, Chowdhury Nowreen, Bristy Anika Tabassum, Emran Tushar, Karim Reatul, Ahmed Rezwana, Shaki Md Mostaid, Sharkar Shazid Md, Sayedur Rahman G M, Reza Hasan Mahmud
Department of Pharmaceutical Sciences, North South University, Dhaka 1229, Bangladesh.
Department of Pharmaceutical Sciences, North South University, Dhaka 1229, Bangladesh.
Biomed Pharmacother. 2024 Dec;181:117703. doi: 10.1016/j.biopha.2024.117703. Epub 2024 Nov 24.
Hypertensive rats serve as a good experimental model for studying the pathophysiology of cardiac hypertrophy and remodeling leading to heart failure. In this study, we aimed to analyze the effect of astaxanthin and possible mechanisms involved in alleviating oxidative stress, fibrosis and inflammation that triggers cardiac remodeling using male uninephrectomized Long Evans rats. Cardiac hypertrophy and hypertension were induced in rats termed as 'FCA-Salt rats' by an oral administration of fludrocortisone acetate (FCA) and 1 % NaCl in drinking water. Biochemical assays showed that FCA-Salt rats exhibited an upregulation of oxidative stress markers AOPP, MDA and downregulation of NO in heart and kidney, which was reversed by astaxanthin treatment. Astaxanthin further regularized the reduced activities of antioxidant enzymes GSH, SOD and CAT in these tissues. ELISA revealed that astaxanthin significantly reduced the inflammatory response by reducing the elevated levels of IL-1β, IL-17a, and TNF-α and pro-fibrotic marker TGF-β1 in plasma. Real-time qPCR depicted an upregulation of TNF-α, IL-1β, IL-6, IL-17A as well as signaling molecules TGF-β1, Smad2 and Smad3 in heart of FCA-Salt rats, which was reduced significantly by astaxanthin. Sirius red staining showed that the cardiac and renal fibrosis was significantly improved by astaxanthin treatment. Together, our results suggest that astaxanthin treatment is beneficial in protecting cardio-renal damage in hypertension through TGF-β/Smad signaling pathway, hence, this molecule may be considered for the maintenance of cardio-renal health.
高血压大鼠是研究导致心力衰竭的心脏肥大和重塑病理生理学的良好实验模型。在本研究中，我们旨在分析虾青素的作用以及可能参与减轻氧化应激、纤维化和炎症（这些因素会引发心脏重塑）的机制，实验使用雄性单肾切除的Long Evans大鼠。通过口服醋酸氟氢可的松（FCA）并在饮用水中添加1% NaCl诱导大鼠（称为“FCA - 盐大鼠”）出现心脏肥大和高血压。生化分析表明，FCA - 盐大鼠心脏和肾脏中的氧化应激标志物AOPP、MDA上调，NO下调，而虾青素治疗可使其逆转。虾青素还使这些组织中抗氧化酶GSH、SOD和CAT的活性恢复正常。ELISA显示，虾青素通过降低血浆中升高的IL - 1β、IL - 17a和TNF - α水平以及促纤维化标志物TGF - β1，显著减轻了炎症反应。实时定量PCR显示，FCA - 盐大鼠心脏中TNF - α、IL - 1β、IL - 6、IL - 17A以及信号分子TGF - β1、Smad2和Smad3上调，而虾青素可使其显著降低。天狼星红染色显示，虾青素治疗可显著改善心脏和肾脏纤维化。总之，我们的结果表明，虾青素治疗通过TGF - β/Smad信号通路对保护高血压中的心脏和肾脏损伤有益，因此，该分子可被考虑用于维持心脏和肾脏健康。
