Intense Endurance Running Training and Supplementation with the Aqueous Extract of Ajwain Seed: Effect on the Levels of Zinc and Some zinc Transporters in the Liver Tissue of Male Wistar Rats
Subject Areas : Journal of Animal BiologyABBAS Ghanbari Niaki 1 , Araz Nazari 2 , Khadije Nasiri 3
1 - Department of Exercise Physiology, Faculty of Sports Sciences, University of Mazandaran, Mazandaran, Babolsar, Iran
2 - Faculty member of Higher educational complex of Saravan, Saravan, Iran
3 - Department of Exercise Physiology, Faculty of Sports Sciences, University of Mazandaran, Mazandaran, Babolsar, Iran
Keywords: High intensity exercise, Supplementation, aqueous extract of Ajwain seed, Slc30a (ZnT), Slc39a (Zip),
Abstract :
Zinc, an essential trace element, plays a crucial role in cellular metabolism. By interacting with numerous proteins, it is essential for a wide range of biological processes, including normal growth, reproduction, DNA synthesis, cell division, gene expression, cell signaling, wound healing, bone formation, and immune system enhancement. The liver plays a central role in zinc metabolism and homeostasis in the body. Zinc concentrations in cells are tightly regulated by two families of zinc transporter proteins, Slc30a (Znt) and Slc39a (Zip), which are known to decrease and increase cytosolic zinc concentration, respectively. Forty male Wistar rats (4-5 weeks old, 189 ± 7.8 g) were randomly assigned to four groups: saline-control (SC), saline-exercise (ST), Ajwain-control (AC), and Ajwain-exercise (AT). Mice in the training group ran on a treadmill at 32 m/min for 60 minutes per session, 5 days a week, for 8 weeks. Mice were received orally (2 g in 10 ml water/kg body weight) and saline groups were treated in the same way. Data analysis was performed using SPSS version 27 software with a two-way ANOVA and Tukey's post hoc test. Ajwain supplementation significantly increased Znt5 and Zip8 gene expression compared to saline groups. Zinc levels and Znt6 and Zip7 gene expression did not show significant changes. Simultaneous implementation of exercise and supplementation with aqueous extract of fennel seeds may modulate zinc levels as well as the gene expression of some zinc transporters in the liver. These findings may provide novel insights into the underlying mechanisms of exercise and nutrition effects on liver tissue.
1. Asif H.M., Sultana S., Akhtar N. 2014. A panoramic view on phytochemical, nutritional, ethanobotanical uses and pharmacological values of Trachyspermum ammi Linn. Asian Pacific Journal of Tropical Biomedicine, 4:S545-S553.
2. Aydemir T.B., Liuzzi J.P., McClellan S., Cousins R.J. 2009. Zinc transporter ZIP8 (SLC39A8) and zinc influence IFN-γ expression in activated human T cells. Journal of leukocyte biology, 86(2):337-348.
3. Barman S., Pradeep S.R., Srinivasan K. 2017. Zinc supplementation mitigates its dyshomeostasis in experimental diabetic rats by regulating the expression of zinc transporters and metallothionein. Metallomics, 9(12):1765-1777.
4. Begum N.A., Kobayashi M., Moriwaki Y., Matsumoto M., Toyoshima K., Seya T. 2002. Mycobacterium bovis BCG cell wall and lipopolysaccharide induce a novel gene, BIGM103, encoding a 7-TM protein: identification of a new protein family having Zn-transporter and Zn-metalloprotease signatures. Genomics, 80(6):630-645.
5. Bellomo E.A., Meur G., Rutter G.A. 2011. Glucose regulates free cytosolic Zn2+ concentration, Slc39 (ZiP), and metallothionein gene expression in primary pancreatic islet β-cells. Journal of Biological Chemistry, 286(29):25778-25789.
6. Boughammoura S., Ben Mimouna S., Chemek M., Ostertag A., Cohen-Solal M., Messaoudi I. 2020. Disruption of bone zinc metabolism during postnatal development of rats after early life exposure to cadmium. International Journal of Molecular Sciences, 21(4):1218-1239.
7. Cemek M., Büyükokuroğlu M.E., Sertkaya F., Alpdağtaş S., Hazini A., Önül A., Göneş S. 2014. Effects of food color additives on antioxidant functions and bioelement contents of liver, kidney and brain tissues in rats. Journal of Food and Nutrition Research, 2(10):686-691.
8. Cherasse Y., Urade Y. 2017. Dietary zinc acts as a sleep modulator. International Journal of Molecular Sciences, 18(11):2334-2346.
9. Chu A., Petocz P., Samman S. 2018. Zinc status at baseline is not related to acute changes in serum zinc concentration following bouts of running or cycling. Journal of Trace Elements in Medicine and Biology, 50:105-110.
10. Dashti A., Ghanbari-Niaki A., Nasiri K., Dashty H. 2024. Zinc Transporters in the Livers of Healthy Male Wistar Rats: An Investigation of the Effects of Aerobic Exercise and Supplementation with Pumpkin Seed and White Pea. Zahedan Journal of Research in Medical Sciences, 26(1):e137982.
11. Foster M., Petocz P., Samman S. 2013. Inflammation markers predict zinc transporter gene expression in women with type 2 diabetes mellitus. The Journal of Nutritional Biochemistry, 24(9):1655-1661.
12. Fukunaka A., Kurokawa Y., Teranishi F., Sekler I., Oda K., Ackland M.L., Faundez V., Hiromura M., Masuda S., Nagao M. 2011. Tissue nonspecific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway. Journal of Biological Chemistry, 286(18):16363-16373.
13. Ganapathy S., Volpe S.L. 1999. Zinc, exercise, and thyroid hormone function. Critical Reviews in Food Science and Nutrition, 39(4):369-390.
14. Ghanbari-Niaki A., Ghanbari-Abarghooi S., Rahbarizadeh F., Zare-Kookandeh N., Gholizadeh M., Roudbari F., Zare-Kookandeh A. 2013. Heart ABCA1 and PPAR-α genes expression responses in male rats: effects of high intensity treadmill running training and aqueous extraction of black crataegus-pentaegyna. Research in Cardiovascular Medicine, 2(4):153-167.
15. Ghanbari-Niaki A., Rahmati-Ahmadabad S. 2013. Effects of a fixed-intensity of endurance training and pistacia atlantica supplementation on ATP-binding cassette G4 expression. Chinese Medicine, 8(1):1-9.
16. Ghio A.J., Soukup J.M., Ghio C., Gordon C.J., Richards J.E., Schladweiler M.C., Snow S.J., Kodavanti U.P. 2021. Iron and zinc homeostases in female rats with physically active and sedentary lifestyles. Biometals, 34:97-105.
17. Gholizade A. 2022. The effect of aerobic exercise and supplementation with pumpkin seed and white pea oil on the expression of zinc transporter genes (ZnT8, ZIP8) and antioxidant enzyme genes in liver and muscle tissue of male rats. PhD Theses, Bobolsar: Mazandaran Univercity. [In Persian].
18. Grüngreiff K., Reinhold D., Wedemeyer H. 2016. The role of zinc in liver cirrhosis. Annals of Hepatology, 15(1):7-16.
19. Huang L., Kirschke C.P., Gitschier J. 2002. Functional characterization of a novel mammalian zinc transporter, ZnT6. Journal of Biological Chemistry, 277(29):26389-26395.
20. Huang L., Kirschke C.P., Zhang Y., Yu Y.Y. 2005. The ZIP7 gene (Slc39a7) encodes a zinc transporter involved in zinc homeostasis of the Golgi apparatus. Journal of Biological Chemistry, 280(15):15456-1563.
21. Jackson M.A., Slininger P.J., Bothast R. 1989. Effects of zinc, iron, cobalt, and manganese on Fusarium moniliforme NRRL 13616 growth and fusarin C biosynthesis in submerged cultures. Applied and Environmental Microbiology, 55(3):649-655.
22. Kambe T. 2012. Molecular architecture and function of ZnT transporters. Current topics in membranes, 69:199-220.
23. Kambe T. 2016. Regulation of zinc transport. Encyclopedia of Inorganic and Bioinorganic Chemistry; Culotta, V, Scott, RA, Eds:301-309.
24. Kambe T., Narita H., Yamaguchi-Iwai Y., Hirose J., Amano T., Sugiura N., Sasaki R., Mori K., Iwanaga T., Nagao M. 2002. Cloning and characterization of a novel mammalian zinc transporter, zinc transporter 5, abundantly expressed in pancreatic β cells. Journal of Biological Chemistry, 277(21):19049-19055.
25. Kambe T., Suzuki E., Komori T. 2019. Zinc Transporter Proteins: A Review and a New View from Biochemistry. In: Fukada, T., Kambe, T. (eds) Zinc Signaling. Springer, Singapore, pp:23-56.
26. Kusakabe T., Nakajima K., Suzuki K., Nakazato K., Takada H., Satoh T., Oikawa M., Kobayashi K., Koyama H., Arakawa K. 2008. The changes of heavy metal and metallothionein distribution in testis induced by cadmium exposure. Biometals, 21:71-81.
27. Lasry I., Golan Y., Berman B., Amram N., Glaser F., Assaraf Y.G., 2014. In situ dimerization of multiple wild type and mutant zinc transporters in live cells using bimolecular fluorescence complementation. Journal of Biological Chemistry, 289(11):7275-7292.
28. Liu M.-J., Bao S., Gálvez-Peralta M., Pyle C.J., Rudawsky A.C., Pavlovicz R.E., Killilea D.W., Li C., Nebert D.W., Wewers M.D. 2013. ZIP8 regulates host defense through zinc-mediated inhibition of NF-κB. Cell Reports, 3(2):386-400.
29. Mashreghi S. 2022. The effect of running exercise at two different intensities with and without red safflower extract supplementation on the expression of zinc transporter genes (ZnT5 and ZIP8) in heart and liver tissue and zinc and iron levels in selected tissues in male rats. MCs Theses. Babolsar: Mazandaran Univercity. [In Persian].
30. Myers S.A., Nield A., Chew G.S., Myers M.A. 2013. The zinc transporter, Slc39a7 (Zip7) is implicated in glycaemic control in skeletal muscle cells. PLoS One, 8(11):e79316.
31. Ni H., Li C., Feng X., Cen J. 2011. Effects of forced running exercise on cognitive function and its relation to zinc homeostasis-related gene expression in rat hippocampus. Biological Trace Element Research, 142:704-712.
32. Noh H., Paik H.Y., Kim J., Chung J. 2014. The changes of zinc transporter ZnT gene expression in response to zinc supplementation in obese women. Biological Trace Element Research, 162:38-45.
33. Handa S.S. 2008. An overview of extraction techniques for medicinal and aromatic plants. Extraction Technologies for Medicinal and Aromatic Plants, 1(1):21-40.
34. Qin Y., Dittmer P.J., Park J.G., Jansen K.B., Palmer A.E. 2011. Measuring steady-state and dynamic endoplasmic reticulum and Golgi Zn2+ with genetically encoded sensors. Proceedings of the National Academy of Sciences, 108(18):7351-7356.
35. Rasmussen S.E., Andersen N.L., Dragsted L.O., Larsen J.C. 2006. A safe strategy for addition of vitamins and minerals to foods. European Journal of Nutrition, 45:123-135.
36. Sauer A.K., Malijauskaite S., Meleady P., Boeckers T.M., McGourty K., Grabrucker A.M. 2022. Zinc is a key regulator of gastrointestinal development, microbiota composition and inflammation with relevance for autism spectrum disorders. Cellular and Molecular Life Sciences, 79(1):46.
37. Soleimantabar Z. 2023. The effect of 8 weeks of running on a treadmill and Yari supplementation with aqueous extract of fennel seeds on the expression of selected mucin genes and the level of glycogen in the digestive tract in male rats. MCs Theses. Babolsar: Mazandaran Univercity. [In Persian].
38. Suzuki T., Ishihara K., Migaki H., Matsuura W., Kohda A., Okumura K., Nagao M., Yamaguchi-Iwai Y., Kambe T. 2005. Zinc transporters, ZnT5 and ZnT7, are required for the activation of alkaline phosphatases, zinc-requiring enzymes that are glycosylphosphatidylinositol-anchored to the cytoplasmic membrane. Journal of Biological Chemistry, 280(1):637-643.
39. Taylor K.M., Hiscox S., Nicholson R.I., Hogstrand C., Kille P. 2012. Protein kinase CK2 triggers cytosolic zinc signaling pathways by phosphorylation of zinc channel ZIP7. Science Signaling, 5(210):ra11.
40. Wang X., Zhang M., Ma J., Tie Y., Wang S. 2024. Biochemical Markers of Zinc Nutrition. Biological Trace Element Research, doi: 10.1007/s12011-024-04091-x.
41. Xiong L., Zhou B., Young J.L., Wintergerst K., Cai L. 2022. Exposure to low-dose cadmium induces testicular ferroptosis. Ecotoxicology and Environmental Safety, 234:113373.
42. Zhang X., Guan T., Yang B., Chi Z., Wang Z.Y., Gu H.F. 2018. A novel role for zinc transporter 8 in the facilitation of zinc accumulation and regulation of testosterone synthesis in Leydig cells of human and mouse testicles. Metabolism, 88:40-50.