Gastrointestinal Diseases
The dysregulation of iron metabolism, be it deficiency or overload, is commonly seen in individuals with gastrointestinal disorders and can markedly affect the course and intensity of the disease. Protheragen, as one of the foremost research service providers in iron metabolism, offers in-depth and comprehensive solutions in drug development for gastrointestinal diseases, concentrating on the complex relationship involving iron metabolism.
Overview of Gastrointestinal Diseases
Diseases of the gastrointestinal system include all the disorders of the tract, liver, pancreas, and gallbladder. Such illnesses pose a considerable problem in public health, even with commonly occurring disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), as well as more serious illnesses like liver cirrhosis and gastrointestinal cancers.
Iron Metabolism Abnormalities in Gastrointestinal Diseases
Individuals with gastrointestinal disorders often exhibit symptoms of both iron deficiency and iron overload. For example, iron deficiency anemia can arise due to chronic blood loss from the gastrointestinal tract in conditions such as peptic ulcer disease and colorectal cancer. On the other hand, iron overload is also a problem, as it can lead to liver damage, which can lead to cirrhosis and hepatocellular carcinoma. In addition to these more pronounced effects, contributing changes in gastrointestinal cells' iron transport, iron storage, and iron utilization are also important to disease progression and severity.
Fig.1 Iron homeostasis in the intestines. (Sousa Gerós, A., et al., 2020)
Excess iron in the body can initiate ferroptosis, which exacerbates inflammation in the intestine. This is because the liver hormone hepcidin causes ferroportin degradation in the enterocytes, leading to iron accumulation. Excess labile iron in cells can lead to inflammation; in addition, it can cause the peroxidation of lipids, which leads to cell death. The gut microbiota can influence levels of hepcidin and, in turn, also the uptake of iron. In addition, excess iron in the body can disrupt the microbiome, which promotes pathogenic bacteria and dysbiosis, which enhances ferroptosis in intestinal cells.
Therapeutics Development for Gastrointestinal Diseases
| Diseases | Drug Name | Mechanism of Action | Targets | Research Phase |
| Acute Liver Injury | Ferrostatin-1 | Radical-trapping antioxidant; prevents the accumulation of reactive oxygen species within membrane lipids and ferroptosis. | Lipid peroxidation | Preclinical |
| Acute Liver Failure (ALF) | Ulinastatin | Activates Nrf2 signaling pathway and reduces lipid peroxidation and iron overload. | SIRT1/Nrf2/HO-1 pathway | Preclinical |
| Fatty Liver | FerroTerminator1 | New chelator of iron; also, prevents lipid peroxidation and ferroptosis mediated by ACSL4. | c-Myc/ACSL4 axis | Preclinical |
| Inflammatory Bowel Disease | Deferasirox | Restoring intestinal microbiota and inhibiting ferroptosis. | Mucosal iron overload | 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
Utilizing advanced technologies and specialized knowledge in iron metabolism, we offer services from discovery to preclinical validation, thereby expediting your drug R & D processes. We offer services relating to the development of advanced diagnostics, innovative therapeutics, and disease models. Our extensive preclinical services also include pharmacokinetics and safety evaluation of your drug candidates prior to application.
- Small Molecule Drug Development
- Cell Therapy Development
- Gene Therapy Development
- Therapeutic Antibody Development
- Therapeutic Peptide Development
- Therapeutic Protein Development
Types of Gastrointestinal Diseases
- Acute and Chronic Liver Injury
- Fatty Liver
- Acute Liver Failure (ALF)
- Hepatic Fibrosis
- Celiac Disease
- Inflammatory Bowel Disease
- Chronic Hepatitis C
- Liver Cirrhosis
Animal Model Development Services for Gastrointestinal Diseases
The animal model development services of our company address the needs of researchers by providing relevant in vivo platforms for the study of diseases of the digestive system and iron metabolism. We apply our knowledge and experience to develop and validate the animal models that achieve the best possible alignment with disease processes and model the necessary therapy responses for high data quality.
| Animal Models | Diseases | Types |
| DSS-induced colitis model | Inflammatory Bowel Disease | Chemical-induced model |
| IL-10 knockout model | Inflammatory Bowel Disease | Genetically engineered model |
| CD4+ T-cell transfer model | Inflammatory Bowel Disease | T-Cell adoptive transfer model |
| High iron diet-induced colitis model | Colitis | Diet-induced model |
| HLA-DQ8 transgenic model | Celiac Disease | Genetically engineered model |
| Gliadin-immunized mouse model | Celiac Disease | Immunologically-induced model |
| CCl4-induced model | Hepatic Fibrosis, Liver Cirrhosis | Chemical-induced model |
| Thioacetamide (TAA)-induced model | Hepatic Fibrosis | Chemical-induced model |
| Bile duct ligation (BDL) model | Hepatic Fibrosis | Surgical animal model |
| Lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced model | Acute Liver Failure (ALF) | Chemical-induced model |
| High-fat diet (HFD)-induced model | Fatty Liver | Diet-induced model |
| Methionine and choline-deficient (MCD) diet-induced model | Fatty Liver | Diet-induced model |
Pharmacokinetics and Drug Safety Evaluation Services
Protheragen stands out with our one-stop service strategy, which ensures tailored service customization for individual clients' requirements. This customized method simplifies research processes and improves the timelines for drug development, enabling us to help you achieve the scientific goals with enhanced efficiency. If you're curious to explore the potential of our expertise in augmenting your research on gastrointestinal disorders and iron metabolism, do reach out to us.
Reference
- Sousa Gerós, Ana et al. "The battle for iron in enteric infections." Immunology 161.3 (2020): 186-199.