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.
Chen Y-H, Feng H-L, Jeng S-S. 2018. Zinc Supplementation Stimulates Red Blood Cell Formation in Rats. International journal of molecular sciences. 19(9): 2824. doi:10.3390/ijms19092824 [Google Scholar] [CrossRef] [PubMed]
Jeng, S.S.; Lo, H.W. High zinc concentration in common carp viscera. Bull. Jpn. Soc. Sci. Fish. 1974, 40, 509. [Google Scholar] [CrossRef]
Jeng, S.S.; Wang, M.S. Isolation of a Zn-binding protein mediating cell adhesion from common carp. Biochem. Biophys. Res. Commun. 2003, 309, 733–742. [Google Scholar] [CrossRef] [PubMed]
Jeng, S.S.; Lin, T.Y.; Wang, M.S.; Chang, Y.Y.; Chen, C.Y.; Chang, C.C. Anoxia survival in common carp and crucian carp is related to high zinc concentration in tissues. Fish. Sci. 2008, 74, 627–634. [Google Scholar] [CrossRef]
Lin, T.Y.; Chen, Y.H.; Liu, C.L.; Jeng, S.S. Role of high zinc levels in the stress defense of common carp. Fish. Sci. 2011, 77, 557–574. [Google Scholar] [CrossRef]
Chen, Y.H.; Fang, S.W.; Jeng, S.S. Zinc transferrin stimulates red blood cell formation in the head kidney of common carp (Cyprinus carpio). Comp. Biochem. Physiol. A Mol. Integr. Physiol. 2013, 166, 1–7. [Google Scholar] [CrossRef] [PubMed]
Chen, Y.H.; Chen, H.H.; Jeng, S.S. Rapid renewal of red blood cells in the common carp following prolonged exposure to air. Fish. Sci. 2015, 81, 255–265. [Google Scholar] [CrossRef]
Chen, Y.H.; Shiu, J.R.; Ho, C.L.; Jeng, S.S. Zinc as a Signal to Stimulate Red Blood Cell Formation in Fish. J. Mol. Sci. 2018 (1)138 doi:10.3390/ijms18010138 [Google Scholar] [CrossRef] [PubMed]