One of the serious complications of diabetes mellitus is diabetic nephropathy (DN) which may finally lead to renal failure. The current study aimed to explore the effect of sulbutiamine, a synthetic derivative of vitamin B1, in streptozotocin (STZ)-induced DN and related pathways. Experimental DN was successfully induced 8 weeks after a single low dose of STZ (45 mg/kg, I.P.). Four groups of rats were used in this study and divided randomly into: control group, diabetic group, sulbutiamine control (control + sulbutiamine) group, and sulbutiamine-treated (60 mg/kg) (diabetic + sulbutiamine) group. The fasting blood glucose level (BGL), the levels of kidney injury molecule-1 (Kim-1), urea and creatinine in serum, as well as the renal content of malondialdehyde (MDA), protein kinase C (PKC), toll-like receptor-4 (TLR-4) and nuclear factor kappa B (NF-κB) were determined. Additionally, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) contents were evaluated immunohistochemically. Sulbutiamine treatment decreased fasting BGL and improved the kidney function tests compared to diabetic rats. Moreover, TLR-4, NF-κB, MDA and PKC contents were substantially reduced following sulbutiamine treatment compared to the diabetic group. Sulbutiamine managed to obstruct the production of the pro-inflammatory TNF-α and IL-1β and suppressed TGF-β1 level, in addition to attenuating the histopathological changes associated with DN. This study revealed, for the first time, the ability of sulbutiamine to ameliorate STZ-induced diabetic nephropathy in rats. This nephroprotective outcome of sulbutiamine against DN may be attributed to glycemic control in addition to its anti-oxidative, anti-inflammatory and anti-fibrotic effects.
Keywords: Anti-fibrotic; Inflammation; Kidney injury molecule-1; Oxidative stress; Protein kinase C; Streptozotocin.
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