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Simple Summary: Type 2 diabetes mellitus (T2DM) is a global health burden that adversely affects various organs, including the brain, leading to neurodegeneration. Recent research emphasizes the cerebellum's role in studying the interactions between T2DM, obesity, aging, and brain energy metabolism. This study focused on the cerebellum of Zucker diabetic fatty (ZDF) rats, a model that mirrors the diversity of T2DM in humans. The primary objective was to measure oxidative stress markers and kinetic properties of sodium–potassium ATPase (Na,K-ATPase) in relation to T2DM severity (not documented yet). Na,K-ATPase is an active transport mechanism crucial for maintaining unequal cation distributions across the plasma membrane, and its activity has been shown to be altered by diabetes in various organs. While oxidative stress is well established in the pathogenesis of diabetes, this study confirmed systemic oxidative and carbonyl damage in ZDF rats and provided new evidence of such damage in cerebellar tissue. However, no differences were found in cerebellar oxidative stress markers based on T2DM severity. Additionally, Na,K-ATPase activity was higher in the cerebellum of ZDF rats compared with controls, suggesting the presence of compensatory mechanisms in this brain region in aged ZDF animals. However, further research is needed to confirm and elucidate this phenomenon. Type 2 diabetes mellitus has been referred to as being closely related to oxidative stress, which may affect brain functions and brain glucose metabolism due to its high metabolic activity and lipid-rich content. Na,K-ATPase is an essential enzyme maintaining intracellular homeostasis, with properties that can sensitively mirror various pathophysiological conditions such as diabetes. The goal of this study was to determine oxidative stress markers as well as Na,K-ATPase activities in the cerebellum of Zucker diabetic fatty (ZDF) rats depending on diabetes severity. The following groups of male rats were used: Wistar, ZDF Lean (fa/+), and ZDF (fa/fa) rats, arbitrarily divided according to glycemia into ZDF obese (ZO, less severe diabetes) and ZDF diabetic (ZOD, advanced diabetes) groups. In addition to basic biometry and biochemistry, oxidative stress markers were assessed in plasma and cerebellar tissues. The Na, K-ATPase enzyme activity was measured at varying ATP substrate concentrations. The results indicate significant differences in basic biometric and biochemical parameters within all the studied groups. Furthermore, oxidative damage was greater in the cerebellum of both ZDF (fa/fa) groups compared with the controls. Interestingly, Na,K-ATPase enzyme activity was highest to lowest in the following order: ZOD > ZO > Wistar > ZDF lean rats. In conclusion, an increase in systemic oxidative stress resulting from diabetic conditions has a significant impact on the cerebellar tissue independently of diabetes severity. The increased cerebellar Na,K-ATPase activity may reflect compensatory mechanisms in aged ZDF (fa/fa) animals, rather than indicating cerebellar neurodegeneration: a phenomenon that warrants further investigation. [ABSTRACT FROM AUTHOR]

The study aimed to characterize the consequences of a 15-week intake of 10% fructose on the kidney, with the focus on oxidative stress markers and properties of the Na,K-ATPase enzyme. Various antioxidants naturally occurring in common food were demonstrated to be protective against fructose-induced deterioration of kidneys. Therefore, we also aimed to observe the effect of 6-week quercetin administration (20 mg/kg/day) that was initiated following the 9-week period of higher fructose intake, by determining the concentration of sodium, potassium, creatinine, urea, and glucose in blood plasma and oxidative status directly in the renal tissue. Kinetic studies of renal Na,K-ATPase were utilized for a deeper insight into the molecular principles of expected changes in this enzyme activity under conditions of presumed fructose-induced renal injury. Fructose intake led to increase in body weight gain, plasma glucose and sodium levels, and deterioration of kidney properties, although some compensatory mechanisms were observable. Quercetin administration improved glycemic control in rats exposed to fructose overload. However, an increase in plasma creatinine, a decrease in GSH/GSSG ratio in renal tissue homogenate, and a controversial effect on renal Na,K-ATPase enzyme suggest that quercetin treatment may not be beneficial in the condition of pre-existing renal pathology.