Effect of combined administration of SGLT2 inhibitor (dapagliflozin) and cobalamin on kidney-brain axis in type 2 diabetic rats

The hallmark of type II diabetes mellitus (T2DM) is selective microvascular damage, particularly to the kidney and brain, where the connection between them is intricate and bidirectional. This investigation sought to examine cobalamin and dapagliflozin’s effects on the kidney-brain axis in diabetic rats. Five groups of 50 adult male albino rats were randomly and equally assigned to normal control (NC), diabetic non-treated (DN), diabetic cobalamin-treated (D+Cbl), diabetic dapagliflozin-treated (D+Dapa), and diabetic combined cobalamin & dapagliflozin-treated (D+Cbl+Dapa). T2DM was caused by a high-fat diet and a small dosage of streptozotocin. Following the experiment, a neurocognitive assessment was done. Blood pressure was measured. Urine samples were obtained over a 24-hour period to measure albumin and creatinine levels. Blood samples were collected to estimate glycemic state, lipid profile, renal function tests, IL-6, and TAC. HOMA-IR, LDL-C, UACR, and GFR by cystatin C were computed. Sections of the brain and kidney tissues were examined histopathologically. Diabetic rats revealed a significant increase in FBG, HOMA-IR, HbA1c, total cholesterol, triglyceride, LDL-C, blood pressure, and IL-6, and a reduction in serum insulin, HDL-C, and TAC. Also, diabetic rats exhibited neurocognitive and renal dysfunction, accompanied by morphological alterations in the brain and kidneys. Individual therapy with cobalamin or dapagliflozin significantly improved some of these parameters. The neuro-renal protective effect of cobalamin and dapagliflozin when administered together was greater than the effect of either drug alone, indicating a synergistic effect between them. Therefore, cobalamin plus dapagliflozin can be used as a combination treatment for T2DM microvascular insult.