Elucidation of the Secret of How Common Carp Fish Use Zinc to Resist Anoxia Leads to Potential Use of Zinc Supplementation in Anemia Treatment

Significance

The common carp Cyprinus carpio is one of the few species of fish that can tolerate extremely low oxygen levels. Professor Sen-Shyong Jeng and his colleagues found extraordinarily higher zinc levels in the digestive tract tissues (~300 μg/g tissue) of the common carp than in those of other fish (~20 μg/g tissue), as first reported more than 40 years ago (Jeng and Lo, 1974). However, the biological implications of this high level of zinc have only been revealed recently. They found that zinc in the common carp is stored in a specific 43 kDa zinc-specific binding protein present in the digestive tract tissue of the common carp (Jeng and Wang, 2003). When needed, such as under conditions of anoxia, the zinc in the 43-kDa zinc-binding protein is released (Jeng et al., 2008; Lin et al., 2011) and used as a signal to stimulate the formation of new red blood cells (RBCs) in the head kidney of the common carp (Chen et al., 2013, 2015). Other fish lack this specific zinc-binding protein and do not have this mechanism in nature. However, if exogenous zinc is supplied to the fish, zinc may also stimulate erythropoiesis in other fish (Chen et al., 2017).

A decrease in the total amount of RBCs is defined as anemia. Anemia is the most common disorder of the blood, affecting approximately a quarter of people globally. In a recent research paper published in the International Journal of Molecular Science Professor Yen-Hua Chen from Xiamen Medical College, Professor Sen-Shyong Jeng and Miss Hui-Lin Feng from National Taiwan Ocean University hypothesized that if common carp can use zinc to stimulate erythropoiesis, it may be possible to use zinc to stimulate erythropoiesis in humans to treat anemia. Even though humans do not have the specific zinc-binding protein possessed by the common carp, zinc could be supplied exogenously.

Based on the clues from the common carp, authors produced phenylhydrazine (PHZ)-induced anemic rats and injected them with saline or ZnSO4 solution. They found that zinc stimulated red blood formation in rats in vivo. When the rat bone marrow cells were supplemented with ZnCl2, proliferation of new red blood cells (reticulocytes) was observed. In rat bone marrow cells, zinc also stimulated erythropoiesis in vitro.

Anemia results from numerous causes, e.g., iron deficiency, vitamin B12 deficiency, bone marrow failure, chronic disease, and thalassemia. Currently, recombinant human erythropoietin (EPO) is used to treat anemia. In addition to EPO, several erythropoiesis-stimulating agents (ESAs) have been studied and are currently in clinical trials. However, zinc has not been previously reported to be an ESA before this study.

Zinc is considered one of the essential minerals with very little toxicity in humans that plays a vital role in maintaining the normal functioning of the body. Pregnancy, infancy and childhood stages are crucial stages of life when zinc is required for the proper growth and development. It is also known that zinc supplementation might be efficacious for the treatment or prevention of certain diseases. Based on study by National Taiwan Ocean University research group who has been doing extensive zinc research for over four decades, the potential of zinc salts as an inexpensive and effective treatment for anemia is high if the anemia is not derived from bone marrow failure or nutrient deficiency. Zinc is not a foreign compound for humans, and zinc salts are less expensive than other potential ESAs. Indeed the present study might be an important foundation for further studies of zinc salts as a supplement for anemia. The unique process by which common carp use zinc as a tool to defend against low oxygen conditions might offer insights into how zinc salts can be used as an ESA to treat anemia in humans.

 

About the author

Dr. Chen is a professor of Basic Medicine at Xiamen Medical College at Fujian, China. She is currently Director of the Center of Translational Medicine in Xiamen Medical College. She obtained PhD degree from National Taiwan Ocean University at 2008, and completed a postdoctoral fellowship at the Center of Excellence for the Ocean in National Taiwan Ocean University. Her current search is focused on the relationship between zinc and erythropoiesis and its application.

About the author

Hui-Lin Feng is a Ph.D. student in National Taiwan Ocean University. She started her research career in Dr. Sen-Shyong Jeng’s lab in 2015, then graduated from NTOU with M.S. degree in Agriculture in 2017. Now she is working on her PhD thesis in ‘Effect of zinc supplementation on renal anemia and its comparison with EPO treatment’.

About the author

Dr. Sen-Shyong Jeng is currently a Chair Professor at National Taiwan Ocean University (NTOU). He also served as the President of the University (NTOU) from 1981 to 1990. He graduated from Taiwan Provincial Maritime College and received PhD from Kyushu University, Japan. He served as a Research Fellow in Academia Sinica, his main area of research is environmental science and marine biochemistry. Professor Jeng was appointed as the president of Kaohsiung Maritime College in 1976, then appointed as the President of National Taiwan Ocean University in 1981. After his presidency, he continued in studying the ‘Secret of High Zinc in Common Carp’ and extends its application to use zinc supplementation in anemia treatment. Professor Jeng and his colleagues has been doing extensive zinc research for over four decades and published 20 more related papers. In recognition of his research excellence, Professor Jeng was the recipient of Academic Award of Ministry of Education, Republic of China (Taiwan) in 1976.

Reference

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