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Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is also known as nonalcoholic fatty liver disease (NAFLD). It is characterized by the increasing fat deposition in the liver and has become a prominent health issue in the world. Here at Protheragen, we work at the forefront of research as a service provider for diseases concerning iron metabolism, including MASLD. Our services span diagnostics, therapeutics, developing disease models, and conducting preclinical studies, thus streamlining and accelerating the work of researchers and scientists.

Overview of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition characterized by excessive fat deposition in the liver.

It is often associated with metabolic syndromes like obesity, diabetes, hypertension, and hypercholesterolemia. MASLD continues to represent the most prevalent form of chronic liver disease, which includes simple steatosis as well as steatohepatitis capable of progression to cirrhosis and hepatocellular carcinoma. There is compelling evidence linking dysregulation of iron homeostasis to the progression of MASLD.

How oxidative stress and ferroptosis promote liver disease. Fig.1 Oxidative stress, ferroptosis, and liver disease progression. (Gensluckner, S., et al., 2024)

Iron Homeostasis Abnormalities in MASLD

Around one out of three adult individuals with MASLD exhibit some form of abnormality of iron metabolism, which is termed "dysmetabolic iron overload syndrome." Excessive iron in the liver can induce hepatocyte injury and liver dysfunctions by increasing the levels of reactive oxygen species through the Fenton reaction. These reactive oxygen species, including peroxides and free radicals, can harm cellular proteins, lipids, and DNA. Increased hepatic iron overload is further reported to correlate with the severity of hepatic histological features of MASLD, including NASH and hepatic fibrosis.

Intervening in NAFLD by targeting iron metabolism. Fig.2 Modulating iron metabolism for NAFLD intervention. (Chen H., 2022)

Therapeutics Development for MASLD

Drug Name	Mechanism of Action	Targets	NCT Number	Research Phase
Deferoxamine	Chelating excess iron within the liver reduces oxidative stress, inflammation, and fibrosis, thus improving hepatic steatosis and providing protection to liver cells.	Iron chelator	NCT03652467	Phase I
Deferasirox	Excess iron is chelated, thus alleviating iron-induced oxidative stress, inflammation, and liver damage associated with MASLD.	Iron chelator	NCT01033747	Phase II/III
rPR-DFO	Allowing for a safe, prolonged circulation of DFO, while more rapidly eliminating iron chelates from the liver.	Nanochelator	/	Preclinical

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a therapy plan recommendation. For guidance on therapy options, please visit a regular hospital.

Our Services

At Protheragen, we prioritize speeding up the research and development processes concerning MASLD. Using our background knowledge in iron metabolism, we provide one-stop drug development services for MASLD so that researchers and scientists can advance their therapeutic pipelines. We provide one-stop services for diagnostic development, therapeutic development, and disease model development. Our strong preclinical services include pharmacokinetics and drug safety evaluation of your drug candidates prior to commercialization.

Therapeutic Development Services

Animal Model Development Services for MASLD

Our services in developing animal models are tailored to deliver comprehensive models pertaining to the preclinical studies of researchers. We specialize in the generation and characterization of animal models profoundly resembling human MASLD and iron metabolic disorders to ensure the production of dependable data for drug discovery and development processes.

Induced Animal Models

High-fat diet (HFD) induced MASLD model
High-fat, high-carbohydrate diet (HFHCD) induced MASLD model
Methionine choline-deficient (MCD) diet-induced MASLD model
High-iron diet (HID)-induced iron overload model
And more

Genetically Engineered Models

ob/ob mouse model
db/db mouse model
Zucker Fatty rat model
LDLR^-/- model
ApoE^-/- model
Foz^-/- model
Hepatocyte-specific Sirt6 knockout model
ALR knockout model
And more

Pharmacokinetics and Drug Safety Evaluation Services

Pharmacokinetic Research Services
Physiochemical Studies	Bioavailability Studies
In Vitro Metabolism Studies	Metabolite Profiling and Identification Studies
In Vitro Permeability and Transporter Studies	Mass Balance Studies
Drug Absorption Studies	Biliary Excretion Studies
Quantitative Tissue Distribution Studies
Drug Safety Evaluation Services
General Toxicology Evaluation	Phototoxicity Evaluation
Genetic Toxicology Evaluation	Tissue Cross-Reactivity Evaluation
Developmental and Reproductive Toxicity Evaluation	Immunogenicity and Immunotoxicity Evaluation
Safety Pharmacology Evaluation	Toxicokinetics Evaluation
Local Toxicity Evaluation

Collaborate with Protheragen to accelerate your research involving MASLD and take advantage of our specialized knowledge in iron metabolism. Reach out to us now to discover how our complete solutions can aid in meeting your milestones for developing diagnostics and therapeutics.

References

Gensluckner, Sophie et al. "Iron, Oxidative Stress, and Metabolic Dysfunction-Associated Steatotic Liver Disease." Antioxidants (Basel, Switzerland) 13.2 (2024): 208.
Chen, Hanqing. "Iron metabolism in non-alcoholic fatty liver disease: A promising therapeutic target." Liver research 6.4 (2022): 203-213.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

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