Sustained-release mitochondrial protonophore reverses nonalcoholic fatty liver disease in rats
Abstract
As a mitochondrial uncoupler, 2,4-dinitrophenol (DNP) is proven therapeutically effective against nonalcoholic fatty liver disease (NAFLD) by uncoupling oxidation and phosphorylation. However, a major factor that impedes the clinical application of DNP is the significant side effects derived from its frequent hyperthermia and even death. In this study, we developed an injectable liquid crystal gel (DNP-LC-gel) to reduce the toxicity of DNP. DNP-LC-gel achieved sustained release and maintained DNP plasma concentration at an effective drug level. In a rat model of NAFLD, DNP-LC-gel treated rats reduced hepatic steatosis, liver triglyceride content, plasma triacylglycerol (TG) and total cholesterol (TC) content. Compared with DNP solution (DNP-soln), rats after DNP-LC-gel treatment showed no body temperature toxicity and local irritation. All results above indicated that DNP-LC-gel has a great potential for NAFLD therapy.
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Injectable crystal gel of DNP (DNP-LC-gel) reduces hepatic steatosis development and lowers TAG liver levels and total cholesterol content in rats, while body temperature is not increased.
“When used in rats, the treatment reduces hepatic steatosis development and lowers TAG liver levels as well as total cholesterol content, while body temperature is not increased [279].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [279]
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Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases
Demine, S., Renard, P., & Arnould, T. (2019) · Cells · doi:10.3390/cells8080795 · Cited by 476 · see citing works
“When used in rats, the treatment reduces hepatic steatosis development and lowers TAG liver levels as well as total cholesterol content, while body temperature is not increased [279].”
Background
- Authors
- Wei, G., Song, X., Fu, Y., Gong, T., & Zhang, Q.
- Affiliations
- Sichuan University (CN)
- Chengdu Medical College (CN)
- Corresponding author
- Zhang, Quan
- Venue
- International Journal of Pharmaceutics
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 530
- Issue
- 1-2
- Pages
- 230-238
- ISSN
- 0378-5173 (ISSN-L)
- OpenAlex
- W2737430749
- Cited by
- 19
- References
- 31
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 6 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 3
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81690261, 81673359)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- non-alcoholic fatty liver disease, 2,4-dinitrophenol, mitochondrial uncouplers, sustained drug release, liquid crystal gels, hepatic steatosis, plasma drug concentration, triglycerides, total cholesterol
- MeSH terms
- Animals, Delayed-Action Preparations, Gels, Liver, Male, Triglycerides, Rats, Sprague-Dawley, 2,4-Dinitrophenol, Rats, Drug Liberation, Non-alcoholic Fatty Liver Disease
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