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allied
academies
Joint Event on
S e p t e m b e r 1 0 - 1 1 , 2 0 1 8 | D u b l i n , I r e l a n d
TOXICOLOGY AND PHARMACOLOGY
PHARMACEUTICAL CHEMISTRY & DRUG DISCOVERY
&
Global Congress on
International Conference on
Pharma Chem Congress 2018 & Toxicology Congress 2018
Asian Journal of Biomedical and Pharmaceutical Sciences
|
Volume 8
Asian J Biomed Pharmaceut Sci 2018, Volume 8 | DOI: 10.4066/2249-622X-C2-006
MULTIMECHANISTIC ANTIFIBROTIC EFFECT OF IRON CHELATORS:
IMPLICATIONS OF INFLAMMATORY AND FIBROGENIC MEDIATORS
Ebtehal El Demerdash
Ain Shams University, Egypt
Background & Aim:
Iron overload is one of mechanisms by which HCV causes oxidative stress that may contribute to liver
fibrosis and carcinogenesis. The therapeutic benefit of adding iron chelators to treatment regimen of HCV patients are warranted
because: firstly, clinical data reported that excess iron deposits are found in the liver samples from about 20% of HCV-positive
patients. Secondly, hepatic iron load enhances the levels of eukaryotic initiation factor 3, which is essential for HCV translation.
Through an international joint project entitled investigating the coagulation profiles and the role of iron in patients with hepatitis C
virus (HCV): impact of iron chelators in attenuating thrombosis and liver fibrosis, we investigated the potential antifibrotic effects
of different iron chelators, and the underlying mechanisms through studying different oxidative stress, inflammatory and fibrotic
markers.
Methods:
Liver fibrosis was induced using concanavalin A (Con A; 15 mg/kg/w for six weeks, iv) and rats were treated with iron
chelators (deseferoxamine, defriprone or defrasirox) three times per week for six weeks. Histopathology and iron homeostasis
pathwaywereelucidated.Thendifferent oxidativestress, inflammatoryandfibrosismarkerswereassessedsuchashydroxyproline,
TGF-beta, alpha-SMA, CD4, NF-kB, TNF-alpha, iNOS, COX-2, IL6 and INF-γ.
Results:
Collectively, it was found that iron chelators possess potent antifibrotic effects due to their antioxidant and anti-
inflammatory properties as well as maintenance of iron homeostasis.
Conclusion:
The present project may open a new scenario for the clinical usefulness of iron chelators in treatment of liver fibrosis
associated conditions in the future.