Rho-kinase inhibition ameliorates non-alcoholic fatty liver disease in type 2 diabetic rats

Non-alcoholic fatty liver disease (NAFLD) is linked to type 2 diabetes mellitus (T2DM), obesity, and insulin resistance. The Rho/ROCK pathway had been involved in the pathophysiology of diabetic complications. This study was designed to assess the possible protective impacts of the Rho/Rho-associate...

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Bibliographic Details
Published in:	Physiological research Vol. 71; no. 5; pp. 615 - 630
Main Authors:	Elkattawy, H A, Elsherbini, D Ma, Ebrahim, H A, Abdullah, D M, Al-Zahaby, S A, Noser, Y, Hassan, A E-S
Format:	Journal Article
Language:	English
Published:	Czech Republic Institute of Physiology 28-11-2022 Institute of Physiology of the Czech Academy of Sciences
Subjects:	Abdomen Animals Apoptosis Body Weight Carbohydrates Caspase-3 Cholesterol Cytokines Diabetes Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Experimental - complications Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - drug therapy Diet Diet, High-Fat - adverse effects Dyslipidemia Enzyme inhibitors Enzymes Fasting Fatty liver Glucose High density lipoprotein High fat diet Inflammation Inflammation - metabolism Insulin Insulin Resistance Kinases Lipids Liver - metabolism Liver diseases Metabolism Mitochondria Non-alcoholic Fatty Liver Disease - drug therapy Non-alcoholic Fatty Liver Disease - pathology Obesity Oxidation Oxidative stress Pathophysiology Protein kinase Proteins Rats Rho-associated kinase rho-Associated Kinases - metabolism Rodents Triglycerides Tumor necrosis factor-TNF Cairo Egypt United States > US China Egypt
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Summary:	Non-alcoholic fatty liver disease (NAFLD) is linked to type 2 diabetes mellitus (T2DM), obesity, and insulin resistance. The Rho/ROCK pathway had been involved in the pathophysiology of diabetic complications. This study was designed to assess the possible protective impacts of the Rho/Rho-associated coiled-coil containing protein kinase (Rho/ROCK) inhibitor fasudil against NAFLD in T2DM rats trying to elucidate the underlying mechanisms. Animals were assigned into control rats, non-treated diabetic rats with NAFLD, and diabetic rats with NAFLD that received fasudil treatment (10 mg/kg per day) for 6 weeks. The anthropometric measures and biochemical analyses were performed to assess metabolic and liver function changes. The inflammatory and oxidative stress markers and the histopathology of rat liver tissues were also investigated. Groups with T2DM showed increased body weight, serum glucose, and insulin resistance. They exhibited disturbed lipid profile, enhancement of inflammatory cytokines, and deterioration of liver function. Fasudil administration reduced body weight, insulin resistance, and raised liver enzymes. It improved the disturbed lipid profile and attenuated liver inflammation. Moreover, it slowed down the progression of high fat diet (HFD)-induced liver injury and reduced the caspase-3 expression. The present study demonstrated beneficial amelioration effect of fasudil on NAFLD in T2DM. The mechanisms underlying these impacts are improving dyslipidemia, attenuating oxidative stress, downregulated inflammation, improving mitochondrial architecture, and inhibiting apoptosis.
ISSN:	0862-8408 1802-9973
DOI:	10.33549/physiolres.934869