Al Za'abi Mohammed, Al Suleimani Yousuf, Ali Haytham, Ali Badreldin H, Al Maskari Raya
Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Al Khod, Oman.
Department of Animal and Veterinary Sciences, College of Agriculture and Marine Sciences, Sultan Qaboos University, Al Khod, Oman.
Front Pharmacol. 2025 Sep 10;16:1600484. doi: 10.3389/fphar.2025.1600484. eCollection 2025.
Diabetes mellitus (DM) and chronic kidney disease (CKD) are associated with significant morbidity and mortality. Their progression is driven by inflammation, oxidative stress, and apoptosis. In this study, we examined the effects of nine different combinations of gum acacia (GA), melatonin, betaine, and flaxseed-used in pairs or trios-on adenine-induced CKD in streptozotocin (STZ)-induced diabetic rats. Rats treated with adenine and STZ exhibited significant hyperglycemia and CKD manifestations such as elevated plasma levels of cystatin C and indoxyl sulfate, increased urinary levels of N-acetyl-β-D-glucosaminidase (NAG) and NAG/creatinine ratio, and reduced creatinine clearance. Additionally, there was a significant decrease in renalase activity and urine osmolality, alongside a significant increase in IL-1β, IL-6, and TNF-α levels and a decrease in IL-10 levels. Oxidative stress biomarkers including superoxide dismutase, glutathione reductase, total antioxidant capacity, and catalase activities were also significantly impaired. These findings were supported by histopathological changes consistent with CKD. Treatment with the combinations of two or three agents alleviated most of these changes to varying degrees. Notably, the GA-melatonin-betaine combination demonstrated the most significant improvement across all the parameters along with the preservation of the kidney tissue structure. These improvements may partially be explained by the enhanced glycemic control achieved by this combination, in addition to possible synergistic molecular, pharmacokinetic, and pharmacodynamic interactions. These findings support the potential of this combination to attenuate the progression of CKD in the setting of diabetes. However, further mechanistic studies, pharmacokinetic profiling, and long-term toxicity data are necessary to validate its efficacy and safety for clinical use.
糖尿病（DM）和慢性肾脏病（CKD）与显著的发病率和死亡率相关。它们的进展由炎症、氧化应激和细胞凋亡驱动。在本研究中，我们检测了阿拉伯胶（GA）、褪黑素、甜菜碱和亚麻籽九种不同组合（成对或三种组合使用）对链脲佐菌素（STZ）诱导的糖尿病大鼠腺嘌呤诱导的CKD的影响。用腺嘌呤和STZ处理的大鼠表现出显著的高血糖和CKD表现，如血浆胱抑素C和硫酸吲哚酚水平升高、尿N - 乙酰 - β - D - 氨基葡萄糖苷酶（NAG）水平和NAG/肌酐比值增加以及肌酐清除率降低。此外，肾酶活性和尿渗透压显著降低，同时白细胞介素 - 1β、白细胞介素 - 6和肿瘤坏死因子 - α水平显著升高，白细胞介素 - 10水平降低。包括超氧化物歧化酶、谷胱甘肽还原酶、总抗氧化能力和过氧化氢酶活性在内的氧化应激生物标志物也显著受损。这些发现得到了与CKD一致的组织病理学变化的支持。用两种或三种药物组合治疗在不同程度上减轻了这些变化中的大多数。值得注意的是，GA - 褪黑素 - 甜菜碱组合在所有参数上都表现出最显著的改善，同时保留了肾脏组织结构。这些改善可能部分归因于该组合实现的血糖控制增强，以及可能的协同分子、药代动力学和药效学相互作用。这些发现支持了该组合在糖尿病背景下减轻CKD进展的潜力。然而，需要进一步的机制研究、药代动力学分析和长期毒性数据来验证其临床使用的有效性和安全性。
