Beneficial effects of crocodile blood on vascular functions in diabetes

M.Phil.According to the World Health Organization, about 422 million people worldwide have diabetes, which causes 3.8 million deaths each year. Cardiovascular disease is a major cause of death in diabetic patients, who are exposed to 2-4 times higher cardiovascular disease morbidity and mortality. While the currently available medications for diabetes focus on glucose control, they have only modest effects on improving their cardiovascular disease outcomes, with no significant effects on the mortality. Therefore, new approaches targeting cardiovascular health in diabetic patients are thus urgently needed.Crocodile blood, an increasingly popular dietary supplement in recent years, has been suggested to have a diverse variety of benefits to humans, including anti-microbial, anti-viral, anti-oxidative, anti-inflammatory, anti-tumor, anti-anemia and wound healing enhancing effects. However, most results on crocodile blood have been limited to in vitro level of studies, with a need for more in vivo experiments to explore the physiological impact and the clinical significance of crocodile blood as a potential medication or supplement.Based on the suggested properties of crocodile blood, it was hypothesized that crocodile blood may benefit cardiovascular health through anti-oxidation and anti-inflammation. In the present study, the effects of oral crocodile blood treatment on vascular function were studied in vivo primarily by examining the endothelium-dependent relaxation, which is an indicator for endothelial function, of the isolated aortae from crocodile blood-treated mice.Despite that crocodile whole blood failed to elicit significant positive effects on the endothelium-dependent relaxation, oral treatment of the soluble fraction of crocodile blood improved endothelial function in db/db mouse aortae with reduced level of reactive oxygen species. Direct effects on endothelial function were also observed from ex vivo organ culture experiments on mouse aortae and in vitro cell culture experiments on endothelial cells. These effects were accompanied by upregulation of the anti-oxidative mitochondrial uncoupling protein 2 (UCP2), which reversed the endothelial dysfunction induced by high oxidative stress in hyperglycemic condition, and the pleiotropic sirtuin 6 (SIRT6) which is defensive against inflammation, oxidative stress and hyperglycemic damage. This study thus suggests a protective role of crocodile blood soluble fraction on vascular endothelial health possibly through regulating the inflammation and oxidative stress in diabetic condition.時至今日，全球約有超過4.2億名糖尿病患者。統計數據顯示，每年死亡人數超過380萬人，其中一大主因就是糖尿病引致的心血管疾病。然而，現有的糖尿病藥物多旨在控制血糖，卻未能有效改善糖尿病人心血管病的病發情況及降低死亡率。因此，我們有必要研發新方法，藉以提升及加強保護糖尿病人的心血管健康狀況。近年，鱷魚血成為一個新興的營養保養品。很多試管實驗指出鱷魚血具有眾多功效，包括殺菌、消毒、抗氧、消炎、抗癌、補血及癒合傷口等，但卻未有足夠活體實驗，以全面了解鱷魚血對人體的影響及其作為藥物或營養補充品的臨床意義。就上所述，我們假設鱷魚血所具有抗氧及消炎的特性，可藉此幫助糖尿病人改善心血管健康狀況。本研究以檢測內皮依賴性舒張反應為主要方法，測試以灌胃方式連續餵食鱷魚血數星期後，小鼠大動脈內皮功能受其影響的程度。結果發現，儘管鱷魚血全血對內皮依賴性舒張反應沒有明顯效果，餵食鱷魚血的水溶性部分，卻能有效改善糖尿病小鼠的內皮功能，以及降低血管內活性氧化物質濃度。此外，體外器官培養和內皮細胞實驗亦發現鱷魚血的水溶性部分能藉由減少活性氧化物質濃度和炎症因子，並增加有益因子UCP2及SIRT6的表達，來針對內皮功能起到保護作用。總括而言，本研究指出鱷魚血的水溶性部分能通過抗氧及消炎效果，減低糖尿病對血管內皮功能的不良影響。Chook, Chui Yiu.Thesis M.Phil. Chinese University of Hong Kong 2020.Includes bibliographical references (leaves 63-71).Abstracts also in Chinese.Title from PDF title page (viewed on January 19, 2022)