The Renoprotective Effect of Atorvastatin in a Rat Model of High-Fat High-Fructose Diet-Induced Renal Injury

Abstract

High-fat diets (HFDs) and sedentary lifestyles are associated with obesity, a significant global health issue that affects over 30% of people in industrialized countries. It is associated with metabolic syndrome, type 2 diabetes, high cholesterol levels, and abnormal lipid metabolism. High-fructose diets can lead to type 2 diabetes, insulin resistance, and inflammation in fat tissue. Statins, particularly hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, have been used to treat obesity and diabetes, but their impact on kidney damage in obese rats is limited. This research aimed to investigate the impact of atorvastatin on renal damage resulting from a high-fat, high-fructose diet (HF-HFrD) in rats. This study involved 24 adult male Sprague Dawley rats, divided into four groups: the control group, the atorvastatin (Ator) group, the high-fat-high-fructose diet (HF-HFr) group, and the high-fat-high-fructose diet with atorvastatin (HF-HFr + Ator) group. Rats were anesthetized, weighed, and sacrificed, and blood was collected from the abdominal aorta and kidneys. Biochemical studies were performed to detect serum urea, creatinine, glucose, insulin, lipid profile, malondialdehyde (MDA) levels, and reduced glutathione (GSH) activity. The histopathological evaluation included H&E, Sirius red staining, NF-κB, and caspase-3 immunohistochemical staining. The HF-HFrD group had elevated levels of serum glucose, insulin, HOMA-IR, creatinine, BUN, cholesterol, and triglycerides while showing a reduction in HDL. The renal tissue exhibited increased levels of MDA, decreased levels of GSH, higher collagen accumulation, and increased expression of NF-κB and caspase-3. Atorvastatin therapy effectively improved these alterations in comparison to the HF-HFrD group. In conclusion, atorvastatin improved HF-HFrD-induced renal injury by modulating lipotoxicity, oxidative stress, inflammation, and apoptosis. Atorvastatin may have therapeutic potential for obesity-related kidney damage.