Effects of Curcumin on Iron Overload in Rats

Background: Iron overload, common in patients with hematological disorders, is a key target in drug development. This study investigated the effects of curcumin on iron overload in rats. Methods: Forty male Wistar rats weighing 139.78 ± 11.95 gm (Mean ± SD) were divided into three equal groups: (i) controls; (ii) iron overload group that received six doses of iron dextran 1000 mg/kg–1 by intraperitoneal injections (i.p.); and (iii) iron overload curcumin group that received six doses of curcumin (1000 mg/kg BW by i.p.). In addition to six doses of iron dextran 1000 mg/kg–1 by i.p., we studied the effects of curcumin on liver function enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]); antioxidant enzymes (malondialdehyde [MDA], total oxidant status [TOS], total antioxidant status [TAS]); hematological parameters (hemoglobin [Hb], hematocrit [Hct], red blood cells [RBC], white blood cells [WBC], mean corpus volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC]); and iron parameters (serum iron profile, transferrin, total iron-binding capacity [TIBC], ferritin, and transferrin saturation [TS%]). Results: Curcumin caused a significant decrease in the Hct and Hb concentrations in Group III (P < 0.05). It also significantly reduced the serum levels of ALT (52.45 ± 4.51 vs 89.58 ± 4.65 U/L) and AST (148.03 ± 6.47 vs 265.27 ± 13.02 U/L) at the end of the study (P < 0.05). The TIBC, transferrin levels, and TS significantly decreased when the rats were administered curcumin serum iron (P < 0.05). The TAS level significantly increased in Group III in comparison to Group I (the control group) (P < 0.05). At the end of the study, curcumin significantly reduced the serum levels of TOS (12.03 ± 2.8 vs 16.95 ± 5.05 mmol H2O2/L) while the TAS (1.98 ± 0.42 vs 1.06 ± 0.33 mmol Trolox equiv./L) was increased. Conclusion: The findings of the present study suggest the therapeutic potential of curcumin against iron overload.

The effect of iron dextran injection on oral candidiasis symptoms in experimental iron deficiency anemia of laboratory rats

Iron deficiency anemia (IDA) is the most common type of anemia that causes various health problems and is commonly companied by oral symptoms, including oral thrush from Candida infection. The study assessed the role of iron status in the pathogenicity of oral candidiasis in an animal model. IDA in rats was produced by feeding on iron-free diet (five weeks), followed by inducing oral candidiasis by Candida albicans suspension. After the infection, animal subgroups were treated by intramuscular injection (IM) of iron dextran (ID) at 2 and 4 mg/kg once a week for three weeks and normal saline injection for comparison. Blood parameters test and tongue histopathological study were conducted. The IDA parameters and the oral thrush lesions were detected in experimental rats. IM of 2 mg ID diminished oral white patches and improved blood hemoglobin (14.533 g/dl), serum iron (109.177 μg/dl), and serum ferritin (5.276 ng/ml) and decreased total iron-binding capacity (377.000 μg/dl). Tongue sections showed normal tongue papillae, reduced inflammation and regular keratin deposition on papillae. At a 4 mg dose, despite the improvement in the blood parameters, a mild reduction was found in tongue thrush by less normal appearance of tongue papillae sections, mild inflammatory cells and hyperplasia of squamous epithelium. The study findings indicate that iron status plays a critical role in the treatment of oral thrush infection.

Effect of Oral Iron Therapy in Moderately Affected Anemianic Pregnant Women

In India, Iron deficiency anemia is one of the major causes of maternal deaths, over the past years, various oral and intra muscular & intravenous preparations of iron have been used for correction of iron muscular are associated with significant side effects; Intramuscular (Iron dextran) was used as an alternative to oral iron therapy for those who were not compliant to oral therapy. Iron dextran has a lot of side effects such as fever, arthralgia, even anaphylactic reactions extending to pulmonary edema and even death. Further it is not possible to achieve the target rise in Hemoglobin level in a limited time period, when the patient is approaching term. Whereas Intravenous (Iron sucrose complex) is a relatively new drug which is a BOON to medical therapy and is the BEST OPTION of iron therapy when used as an alternative to oral therapy as it restores iron stores more promptly and is able to raise the hemoglobin to satisfactory level .

Hepcidin inhibition improves iron homeostasis in ferrous sulfate and LPS treatment model in mice

Background Hepcidin, a liver-derived peptide, regulates the absorption, distribution, and circulation of iron in the body. Inflammation or iron overload stimulates hepcidin release, which causes the accumulation of iron in tissues. The inadequate levels of iron in circulation impair erythropoiesis. Inhibition of hepcidin may increase iron in circulation and improve efficient erythropoiesis. Activin-like kinase (ALK) inhibitors decrease hepcidin. Methods In this work, we have investigated an ALK inhibitor LDN193189 for its efficacy in iron homeostasis. The effect of LDN193189 treatment was assessed in C57BL6/J mice, in which hepcidin was induced by either ferrous sulfate or lipopolysaccharide (LPS) injection. Results After two hours of treatment, ferrous sulfate increased serum and liver iron, serum hepcidin, and liver hepcidin expression. On the other hand, LPS reduced serum iron in a dose-related manner after six hours of treatment. LDN193189 treatment increased serum iron, decreased spleen and liver iron, decreased serum hepcidin and liver hepcidin expression in ferrous sulfate-treated mice, and increased serum iron in LPS-induced hypoferremia. We observed that ferrous sulfate caused a significantly higher increase in liver iron, serum hepcidin, and liver hepcidin than turpentine oil or LPS in mice. Iron dextran (intraperitoneal or intravenous) increased serum iron, but LDN193189 did not show hyperferremia with iron dextran stimulus. Conclusion Ferrous sulfate-induced hyperferremia can be a valuable and rapid screening model for assessing the efficacy of hepcidin inhibitors.

Comparative effectiveness of iron-containing drugs for the prevention of iron deficiency anemia in piglets

Prevention of iron deficiency anemia in piglets is an important preventive measure to ensure the health of pigs, as mortality from this pathology is quite high, and animals that recover from treatment do not realize their own potential productivity. The aim of our study was to evaluate the effectiveness of the use of iron (IV) clatrochelate in combination with cyanocobalamin for the prevention of iron deficiency anemia in piglets compared to the traditional scheme of prevention of this disease. To achieve this goal, 2 groups of newborn piglets-analogues were formed during their retention with suckling sows – control and experimental, 15 animals in each. The experiment lasted 30 days. Piglets in the experimental group were selected from sows given 10 ml of 10 % iron (IV) clatrochelate solution and cyanocobalamin solution twice intramuscularly during pregnancy. Piglets of the control group according to the traditional scheme of prevention of iron deficiency anemia on the second day of life were administered iron dextran drug (at the rate of 200 mg of iron (III) per injection). The results of the study show that the body weight of piglets from 1 to 9 days of their life who are born from sows which used iron (IV) clatrochelate and cyanocobalamin during pregnancy was less (P < 0.001) than the body weight of piglets which used iron dextran on the 2nd day after birth; did not differ on the 12 day of life, but on the 30 day was higher than the body weight of piglets in the control group 1.15 times (P < 0.001). The level of protein in the serum of piglets of the experimental group from birth to 30 day of life was probably higher compared to the control, which indicates that iron (IV) clatrochelate stimulates protein synthesis in the body. Therefore, double injection of 10 % solution of iron (IV) clatrochelate in a dose of 10 ml in combination with injections of cyanocobalamin at a dose of 500 mcg of active substance to pregnant sows pregnant sows 14 and 7 days before the expected farrowing provides a preventive effect of iron deficiency anemia in piglets born to them.

The hypoferremic response to acute inflammation is maintained in thalassemia mice even under parenteral iron loading

Background Hepcidin controls iron homeostasis by inducing the degradation of the iron efflux protein, ferroportin (FPN1), and subsequently reducing serum iron levels. Hepcidin expression is influenced by multiple factors, including iron stores, ineffective erythropoiesis, and inflammation. However, the interactions between these factors under thalassemic condition remain unclear. This study aimed to determine the hypoferremic and transcriptional responses of iron homeostasis to acute inflammatory induction by lipopolysaccharide (LPS) in thalassemic (Hbbth3/+) mice with/without parenteral iron loading with iron dextran. Methods Wild type and Hbbth3/+ mice were intramuscularly injected with 5 mg of iron dextran once daily for two consecutive days. After a 2-week equilibration, acute inflammation was induced by an intraperitoneal injection of a single dose of 1 µg/g body weight of LPS. Control groups for both iron loading and acute inflammation received equal volume(s) of saline solution. Blood and tissue samples were collected at 6 hours after LPS (or saline) injection. Iron parameters and mRNA expression of hepcidin as well as genes involved in iron transport and metabolism in wild type and Hbbth3/+ mice were analyzed and compared by Kruskal–Wallis test with pairwise Mann–Whitney U test. Results We found the inductive effects of LPS on liver IL-6 mRNA expression to be more pronounced under parenteral iron loading. Upon LPS administration, splenic erythroferrone (ERFE) mRNA levels were reduced only in iron-treated mice, whereas, liver bone morphogenetic protein 6 (BMP6) mRNA levels were decreased under both control and parenteral iron loading conditions. Despite the altered expression of the aforementioned hepcidin regulators, the stimulatory effect of LPS on hepcidin mRNA expression was blunt in iron-treated Hbbth3/+ mice. Contrary to the blunted hepcidin response, LPS treatment suppressed FPN1 mRNA expression in the liver, spleen, and duodenum, as well as reduced serum iron levels of Hbbth3/+ mice with parenteral iron loading. Conclusion Our study suggests that a hypoferremic response to LPS-induced acute inflammation is maintained in thalassemic mice with parenteral iron loading in a hepcidin-independent manner.