Iron overload intolerance in Balb/c mice
Noriyuki Koibuchi, Suthat Fucharoen in Advances in Biomolecular Medicine, 2017
The iron–diabetes hypothesis has been supported by a number of epidemiological studies showing that body iron deposits are positively associated with blood glucose levels. The underlying pathological interactions between iron and glucose homeostasis are not well understood. A recent study used C57BL/6 mice that were injected with a high dose of iron to establish an iron overload mouse model. However, in Indonesia, most of the experiments involving mouse models use the Balb/c strain instead of C57BL/6. The objective of this study was to validate the effects of iron overload in Balb/c mice. Mice were intraperitoneally injected with iron dextran (10 mg/μL per day, iron overload group). Fasting blood glucose level, body weight, and liver weight were measured after 7 days of treatment. After 7 days, only six out of 12 mice survived. The body weights of the iron overload group were 18.5% lower than that of the control group, with liver enlargement and lower blood glucose levels. In conclusion, our study indicated that Balb/c mice are intolerant to excessive amounts of iron.
Iron-chelating effect of
Noriyuki Koibuchi, Suthat Fucharoen in Advances in Biomolecular Medicine, 2017
This study aims to obtain the effective dose of sappan wood extract ( Caesalpinia sappan L.) that serves as a herbal chelating agent. An experiment with a Completely Randomized Design (CRD) was conducted on 21 male rats of 8 weeks old. The rats were given oral iron dextran and sappan wood extract at different doses for 15 days. Iron-related blood parameters were measured. The result revealed that a sappan wood extract dose of 200 mg/kg body weight had a chelating effect, showing a decline in ferritin levels (55.6%), a reduction in serum iron levels by 60%, and a reduction in transferrin saturation levels (84.7%). We also found an increase in transferrin levels (66.2%), and TIBC levels (62%) compared with rats given iron dextran injection alone. In conclusion, our study showed that a sappan wood extract dose of 200 mg/kg body weight has an ability to chelate excess iron in rats under conditions of iron overload.
HAEMOCHROMATOSIS
S.H.C. Anderson, H.R. Dalton, G. Davies in Key Topics in Gastroenterology, 1998
Genetic haemochromatosis is an autosomal recessive inborn error of metabolism, in which there is excessive inappropriate intestinal iron absorption over many years, causing tissue iron overload and damage. It is one of the commonest singlegene disorders. The genetic defect lies on the short arm of chromosome 6. Recent genetic studies have shown that up to 0.3% of caucasians are homozygous (and are therefore affected clinically) and 8-10% are heterozygous (these are carriers, having only a mild elevation of serum iron indices and not at risk of tissue injury). The mechanism of excessive iron absorption is unknown. Increased alcohol intake is known to increase the accumulation of iron in affected patients.
Evidence that iron-overload promotes 7, 12-dimethylbenz(a)anthracene-induced skin tumorigenesis in mice
Published in Redox Report, 1997
Summary Iron overload is known to occur in West European and American populations due to the consumption of an iron-rich diet. There are also genetic disorders which lead to body iron overload. It has been shown that iron overload predisposes humans to an increased risk of cancer. In experimental animals, iron overload is known to enhance intestinal, colon, hepatic, pulmonary and mammary carcinogenesis. However, the mechanism by which iron overload enhances chemically-induced carcinogenesis is not known. In this study, we show that iron overload acts as a mild tumor promoter in mouse skin. Female albino swiss mice were given 1 mg iron/mouse parenterally for 2 weeks to induce iron overload. These animals showed a three-fold increase in cutaneous iron concentration as compared to normal mice. Tumors were initiated by topically applying 7,12-dimethylbenz(a)anthracene (DMBA). Appearance of the first tumor (latency period), percent tumor incidence and number of tumors/mouse were recorded. When compared to the control group, iron overload mice showed an increased incidence of tumors, from 25%-55% by week 20, and tumors appeared 4 weeks earlier. The number of tumors per mouse was four-fold higher in the iron overload group. The induction of cutaneous ornithine decarboxylase (ODC) activity and [3H]thymidine incorporation in cutaneous DNA were higher in iron overload groups as compared to normal control animals. Similar to other oxidant tumor promoters, iron overload enhanced cutaneous lipid peroxidation and xanthine oxidase activity and decreased catalase activity. Our results indicate that iron overload exerts a mild tumor promoting activity in mouse skin. Our data also show that oxidative stress generated by iron overload plays an important role in the augmentation of cutaneous tumorigenesis. These data may also have implications for the enhanced risk of cancer-induction following UVB exposure of human populations with iron overload.
Evaluation of Hepatic Iron Overload in Chinese Children With β-Thalassemia Major
Published in Pediatric Hematology and Oncology, 2011
Lu-Hong Xu, Jian-Pei Fang, Hong-Gui Xu, Wen-Jun Weng
Patients with β-thalassemia major require long-term blood transfusions, resulting in hepatic iron overload. Thirty-five Chinese children with β-thalassemia major were recruited in the present studies. Hepatic iron overload was evaluated by histological grading. The relationships between hepatic iron overload and both serum biochemical markers and magnetic resonance imaging (MRI) examination were studied. The majority of the patients showed high degrees of hepatic iron overload by histological study. The degree of hepatic iron overload was correlated with serum ferritin (r = .70, P < .01), hyaluronic acid (r = .58, P = .011), and type III precollagen (r = .55, P = .035). Moreover, hepatic iron overload showed a negative correlation with liver to muscle signal intensity ratio (r = −.44, P = .012), and a positive correlation with red marrow area percentage (r = .52, P < .01). These results indicated that hepatic iron overload might be assessed by serum biochemical markers and MRI examination.
Ferroportin-inhibitor salt: patent evaluation WO2018192973
Published in Expert Opinion on Therapeutic Patents, 2021
Snehal Kadam, Megha Khaitan, Paromita Banerjee, Anita Mandhare
ABSTRACT Introduction Iron is a crucial element necessary for blood formation in the body and its normal growth. However, irregular metabolism of iron due to absence of an elimination mechanism may deposit excess iron in the organs (iron overload) leading to metabolic disorders. Interactions between the iron regulatory peptide hormone, hepcidin and the iron exporter ferroportin plays major role in regulating the iron metabolism. Mutations in the ferroportin encoding genes, and dysregulation of hepsidin production often results in iron overload resulting in conditions like hemochromatosis, β-thalassemia, and sickle cell anemia. Until today, there is no efficacious treatment available for managing iron overload targeting ferroportin inhibition via oral administration. Areas Covered Novel salts of substituted benzoimidazole compounds useful for the prophylaxis and/or treatment of iron overload are claimed. These compounds act as hepcidin mimetic and inhibit the ferroportin thereby preventing iron overload. The claimed actives are useful in the treatment of disease conditions such as neurodegenerative and cardiac diseases triggered by iron overload. Preclinical studies of these salts on mouse model are also discussed. Expert Opinion Prevention and/or treatment of iron overload is critical. The claimed compounds are the first oral drug candidate to treat iron overload and reach the pre-clinical development stage.