Investigation of the effects of magnesium biotinate and arginine silicate on kidney tissue and functions in rats fed a high-fat diet

High-fat diet (HFD) and obesity impair renal structure and function via renal lipotoxicity, oxidative stress, and low-grade inflammation, leading to glomerular and tubular injury. In this process, overexpression of SGLT2 (sodium–glucose cotransporter 2), which augments glucose reabsorption, suppression of the organic anion transporter OAT3 (organic anion transporter 3), and dysregulation of metabolic/signaling pathways such as PI3K (phosphoinositide 3-kinase)/AKT (PKB, protein kinase B) and PEPCK (phosphoenolpyruvate carboxykinase) further exacerbate loss of renal function. Magnesium biotinate (MgB), characterized by antioxidant and metabolic regulatory properties, and arginine silicate (ASI), reported to favorably modulate vascular/endothelial function and cellular stress responses, may offer protection along these pathobiological axes. This study aimed to investigate the renoprotective effects of MgB and ASI, alone and in combination, in HFD-induced kidney injury in rats. Following ethics committee approval, forty male Wistar albino rats were randomly allocated into five groups: Control, HFD, HFD+MgB, HFD+ASI, and HFD+MgB+ASI. Renal function was assessed by blood urea nitrogen (BUN), creatinine, and glucose levels; renal tissue protein levels of SGLT2, OAT3, PI3K, p-AKT, and PEPCK were examined. Structural alterations were scored histopathologically using parameters that included glomerular integrity, tubular degeneration, cytoplasmic vacuolization, luminal dilatation, and increased interstitial cellularity. In the HFD group, glucose, BUN, and creatinine increased significantly (p<0,05); histopathology revealed widespread tubular vacuolization, hydropic degeneration, and increased interstitial cellularity; SGLT2 expression was elevated, OAT3 was suppressed, and disruption was detected in the PI3K/AKT/PEPCK axis. Administration of MgB or ASI alone produced marked improvements in biochemical and tissue indices. Histopathological scores were significantly lower than in HFD (p<0,05). The most pronounced improvement occurred with the MgB+ASI combination: functional tests approached control values most closely, SGLT2 decreased while OAT3 increased toward control levels, and adverse effects on PI3K/AKT and PEPCK were attenuated. Histologically, aside from mild tubulointerstitial "changes, no prominent pathology was observed in the combination group, which exhibited the lowest total injury score. Conclusion: In HFD-induced kidney injury, the renoprotective effects of MgB and ASI were confirmed; combination therapy demonstrated the strongest protective impact at biochemical, molecular, and histopathological levels. These data suggest that MgB+ASI may be a promising adjuvant approach for preventing or mitigating metabolic kidney injury these findings should be supported by further translational studies.