Ameliorating Iron Overload in Intestinal Tissue of Adult Male Rats: Quercetin vs Deferoxamine.

Arwa A El-Sheikh,Shimaa Hamed Ameen,Samaa Salah Abdel-Fatah

doi:10.1155/2018/8023840

Abstract

Objective The aim of our study is to compare the role of the new natural alternative (Quercetin) with the current iron-chelation therapy (Deferoxamine (DFO)) in the effect of iron overload on small intestinal tissues and to investigate the possible underlying molecular mechanisms of such toxicity. Methods Forty-two adult male albino rats were divided into six groups: control groups, DFO, Quercetin, iron overload, iron overload+DFO, and iron overload+Quercetin groups. Animals received daily intraperitoneal injection of Deferoxamine (125 mg /kg), Quercetin (10 mg/kg), and ferric dextran (200 mg/kg) for 2 weeks. Results Iron overloaded group showed significant increase in serum iron, total iron binding capacity (TIBC), transferrin saturation percentage (TS %) hepcidin (HEPC), serum ferritin, nontransferrin bound iron (NTBI), and small intestinal tissues iron levels. Iron overload significantly increased the serum oxidative stress indicator (MDA) and reduced serum total antioxidant capacity (TAC). On the other hand, iron overload increased IL6 and reduced IL10 in small intestinal tissues reflecting inflammatory condition and increased caspase 3 reactivity indicating apoptosis and increased iNOs expressing cell indicting oxidative stress especially in ileum. In addition, it induced small intestinal tissues pathological alterations. The treatment with Quercetin showed nonsignificant differences as compared to treatment with DFO that chelated the serum and tissue iron and improved the oxidative stress and reduced tissue IL6 and increased IL10 and decreased caspase 3 and iNOs expressing cells in small intestinal tissues. Moreover, it ameliorated the iron overload induced pathological alterations. Conclusion Our study showed the potential role of Quercetin as iron chelator like DFO in case of iron overload induced small intestinal toxicity in adult rats because of its serum and tissue iron chelation, improvement of serum, and small intestinal oxidative stress, ameliorating iron induced intestinal inflammation, apoptosis, and histopathological alterations.

Highlights

IntroductionIron is essential element in various physiological processes in the body as erythropoiesis, oxidative energy production, mitochondrial respiration, and oxygen transport [1]. the iron is important metal for the function of cells, its excess accumulation causes iron overload that may result from hereditary hemochromatosis and related disorders, secondary iron overload as Ineffective erythropoiesis, and excess oral or parenteral iron overload [2].The iron metabolism is regulated by many factors such as hepcidin, which is peptide hormone that affects iron absorption in small intestine and systemic iron regulation [3]; transferrin (Tf) that bind iron at physiological iron concentrations and nontransferrin bound iron (NTBI) in iron overload concentrations [4]; serum ferritin (SF) and Hemosiderin that reflect the total body iron stores and act as indicative of iron overload [1].Iron overload produce reactive oxygen species (ROS) leading to impairment of cellular function and multiple disorders as anemia, heart failure, liver cirrhosis, kidney injury, fibrosis, diabetes, arthritis, depression, impotency, infertility, and cancer [5]
Regarding the immunohistochemical staining by caspase-3, the examination of small intestinal tissues sections taken from control, Deferoxamine Mesylate (DFO) and Quercetin groups showed weak proapoptotic caspase3staining in both duodenum and ileum (Figure 3(A) and (A1), respectively)
According to the immunohistochemical expressions of inducible nitric oxide synthase, the examination of small intestinal tissues sections taken from control, DFO and Quercetin groups showed few weak positive iNOS-expressing cells and in both duodenum and ileum (Figure 4(A) and (A1), respectively)

Summary

Introduction

Iron is essential element in various physiological processes in the body as erythropoiesis, oxidative energy production, mitochondrial respiration, and oxygen transport [1]. the iron is important metal for the function of cells, its excess accumulation causes iron overload that may result from hereditary hemochromatosis and related disorders, secondary iron overload as Ineffective erythropoiesis, and excess oral or parenteral iron overload [2].The iron metabolism is regulated by many factors such as hepcidin, which is peptide hormone that affects iron absorption in small intestine and systemic iron regulation [3]; transferrin (Tf) that bind iron at physiological iron concentrations and nontransferrin bound iron (NTBI) in iron overload concentrations [4]; serum ferritin (SF) and Hemosiderin that reflect the total body iron stores and act as indicative of iron overload [1].Iron overload produce reactive oxygen species (ROS) leading to impairment of cellular function and multiple disorders as anemia, heart failure, liver cirrhosis, kidney injury, fibrosis, diabetes, arthritis, depression, impotency, infertility, and cancer [5]. Iron is essential element in various physiological processes in the body as erythropoiesis, oxidative energy production, mitochondrial respiration, and oxygen transport [1]. The iron metabolism is regulated by many factors such as hepcidin, which is peptide hormone that affects iron absorption in small intestine and systemic iron regulation [3]; transferrin (Tf) that bind iron at physiological iron concentrations and nontransferrin bound iron (NTBI) in iron overload concentrations [4]; serum ferritin (SF) and Hemosiderin that reflect the total body iron stores and act as indicative of iron overload [1]. Iron overload produce reactive oxygen species (ROS) leading to impairment of cellular function and multiple disorders as anemia, heart failure, liver cirrhosis, kidney injury, fibrosis, diabetes, arthritis, depression, impotency, infertility, and cancer [5].

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Discussion

Conclusion