The effect of Fenofibrate combined with α-Lipoic acid on creatinine and uric acid in rat model of non-alcoholic fatty liver disease
The effect of Fenofibrate combined with α-Lipoic acid on creatinine and uric acid in rat model of non-alcoholic fatty liver disease
Babak Hassankhan,1,*Parichehreh Yaghmaei,2Kazem Parivar,3Azadeh Ebrahim-Habibi,4
1. Department of Biology, Faculty of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran 2. Department of Biology, Faculty of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran. 3. Department of Biology, Faculty of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran 4. Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Introduction: Background and Aim: Non-alcoholic fatty liver disease (NAFLD) connects to chronic kidney disease (CKD) and the prevalence of CKD was significantly higher in NAFLD patients. NAFLD is associated with insulin resistance and hyperlipidaemia. Insulin resistance plays an important role in metabolic syndrome and CKD. Lipoprotein abnormalities such as high triglycerides (TGs), associate with subsequent decline in kidney function. Hyperlipidemia induce oxidative stress, lipotoxicity and immune activation. Insulin resistance and hyperlipidaemia play potential pathogenic role in the development and progression of CKD. Pathogenesis of NAFLD and CKD are complicate and suggests that combination therapy may be more effective for the treatment of NAFLD and CKD. Fenofibrate is one of the most important drugs for the management of dyslipidemia and α-lipoic acid has antioxidant effect. The present study aimed to investigate the effect of fenofibrate in combination with α-Lipoic acid on kidney function and the prevention of hypertriglyceridemia and oxidative stress in rat model of non-alcoholic fatty liver disease.
Methods: Materials and Methods: Forty male Sprague-Dawley rats were divided into five groups (n=8 in each group): normal control group (NC) to receive a standard chow and four high fat diet fed groups that they received a high fat emulsion diet (HFD) alone, (HF group), and in combination with 100 mg/kg fenofibrate, (Fen group), in combination with 60 mg/kg α-Lipoic acid, (Lip group), and in combination with 50 mg/kg fenofibrate plus 30 mg/kg α-lipoic acid, (Fen+Lip group). Animal model of non-alcoholic fatty liver disease was induced by oral gavage of HFD after six weeks. Rats were simultaneously treated with fenofibrate alone and in combination with α-lipoic acid in each group. After this time, the rats were sacrificed. Blood samples were collected for measurement of biochemical parameters includ serum lipid profile, glucose, insulin, insulin resistance (HOMA-IR), liver enzymes, creatinine, uric acid, adiponectin and tumor necrosis factor α (TNF-α). Liver tissue was homogenized for measurement of lipid profile and hepatic malondialdehyde (MDA). Liver histological tests with hematoxylin-eosin staining were performed to evaluate fat accumulation in liver tissue.
Results: Results: After six weeks, the level of lipid profile, blood glucose, insulin, insulin resistance (HOMA-IR), TNF-α, creatinine, uric acid, in serum and hepatic content of malondialdehyde (MDA), and triglyceride (TG) significantly increased (P<0/05) and serum adiponectin significantly decreased in high fat group compared to the normal control group (P<0/05). Liver sections of high fat group displayed obvious fat droplets and macrovesicular steatosis. Hepatic content of MDA was not decrease by fenofibrate (P>0.05). Fenofibrate in combination with α-lipoic acid significantly decreased the hepatic content of MDA in Fen+Lip group compared to the high fat group (P<0.05). Fenofibrate alone did not alter the serum concentrations of creatinine and uric acid in Fen group compared to the HF group (P>0/05) but fenofibrate combined with α-Lipoic acid significantly decreased the serum concentrations of creatinine and uric acid in Fen+Lip group compared to the HF group (P<0/05).
Conclusion: Conclusion: Our results indicate that fenofibrate in combination with α-lipoic acid showed higher protect effect on oxidative stress compared to the fenofibrate alone and fenofibrate with α-lipoic acid can reduc serum concentrations of creatinine and uric acid compared to the fenofibrate alone. These results suggest that combination therapy with fenofibrate and α-Lipoic might provide a beneficial method for treatment of chronic kidney disease and improvement of kidney function.