Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

06 February 2020 : Animal Research  

The Effects of RKI-1447 in a Mouse Model of Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet and in HepG2 Human Hepatocellular Carcinoma Cells Treated with Oleic Acid

Jinshan Wang1ABCDEF, Wentao Jiang1ABCDEFG*

DOI: 10.12659/MSM.919220

Med Sci Monit 2020; 26:e919220


BACKGROUND: This study aimed to investigate the effects of RKI-1447, a selective inhibitor of Rho-associated ROCK kinases, in a mouse model of nonalcoholic fatty liver disease (NAFLD) induced by a high-fat diet, and in oleic acid-treated HepG2 human hepatocellular carcinoma cells in vitro.

MATERIAL AND METHODS: Four study groups of mice included: the control group; the high-fat diet (HFD) group; the HFD+RKI-1447 (2 mg/kg) group; and the HFD+RKI-1447 (8 mg/kg) group. Mice were fed a high-fat diet for 12 weeks. Mice in the HFD+RKI-1447 groups were fed a high-fat diet for 12 weeks and treated with RKI-1447 twice weekly for three weeks. The HepG2 human hepatocellular carcinoma cells were treated with or without RKI-1447 for 2 h and treated with oleic acid for 24 h.

RESULTS: In the mouse model of NAFLD, RKI-1447 reduced insulin resistance and the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total cholesterol, triglyceride, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), and superoxide dismutase (SOD). RKI-1447 reduced the histological changes in the mouse model of NAFLD in mice fed a high-fat diet and significantly inhibited the generations of triglyceride, IL-6, and TNF-α. RKI-1447 reduced the levels of oxidative stress in HepG2 cells treated with oleic acid and significantly down-regulated the expression of RhoA, ROCK1, ROCK2, toll-like receptor 4 (TLR4), p-TBK1, and p-IRF3. RKI-1447 treatment also inhibited RhoA expression.

CONCLUSIONS: In a mouse model of NAFLD, RKI-1447 inhibited ROCK and modulated insulin resistance, oxidative stress, and inflammation through the ROCK/TLR4/TBK1/IRF3 pathway.

Keywords: Diet, High-Fat, Liver Diseases, rho-Associated Kinases, Alanine Transaminase, Aspartate Aminotransferases, Carcinoma, Hepatocellular, Cholesterol, Glucose Tolerance Test, Hep G2 Cells, Insulin Resistance, Interleukin-6, Liver, Liver Neoplasms, Malondialdehyde, Mice, Inbred ICR, Models, Biological, Non-alcoholic fatty liver disease, Oleic Acid, Thiazoles, Triglycerides, Urea, rhoA GTP-Binding Protein



01 March 2023 : Editorial  

Editorial: Global Surveillance of Highly Pathogenic Avian Influenza Viruses in Poultry, Wild Birds, and Mammals to Prevent a Human Influenza Pandemic

Dinah V. Parums

DOI: 10.12659/MSM.939968

Med Sci Monit 2023; 29:e939968


03 March 2023 : Database Analysis  

Reinfections from SARS-CoV-2: A Retrospective Study from the Gyncentrum Genetic Laboratory in Sosnowiec, Po...

Med Sci Monit In Press; DOI: 10.12659/MSM.939452  

09 February 2023 : Clinical Research  

Evaluation of Health-Related Quality of Life and Mental Health in 729 Medical Students in Indonesia During ...

Med Sci Monit 2023; 29:e938892

27 December 2022 : Clinical Research  

Effect of Physiotherapy to Correct Rounded Shoulder Posture in 30 Patients During the COVID-19 Pandemic in ...

Med Sci Monit 2022; 28:e938926

In Press

20 Mar 2023 : Clinical Research  

Management of Unstable C1 Fractures Involving the Lateral Mass: Posterior C1-C2 Screw-Rod Fixation and Fusion

Med Sci Monit In Press; DOI: 10.12659/MSM.938600  

17 Mar 2023 : Clinical Research  

Relationship Between Autonomic Nervous System Activity and Axial Length in Children

Med Sci Monit In Press; DOI: 10.12659/MSM.939451  

15 Mar 2023 : Clinical Research  

Relationship Between Psychological Symptoms and Self-Esteem Levels Before and After Stomach Botox Treatment

Med Sci Monit In Press; DOI: 10.12659/MSM.939618  

15 Mar 2023 : Clinical Research  

Short-Term Patient Outcomes Using the Interlaminar Endoscopic Surgical System Ilessys® Delta System versus ...

Med Sci Monit In Press; DOI: 10.12659/MSM.938477  

Most Viewed Current Articles

13 Nov 2021 : Clinical Research  

Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...

DOI :10.12659/MSM.932788

Med Sci Monit 2021; 27:e932788

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

01 Jan 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750