CRATAEGUS MONOGYNA’NIN, BAKIR KAYNAKLI TOKSİSİTEYE KARŞI SPERM KALİTESİ VE TESTİS OKSİDATİF STRESİ ÜZERİNDEKİ KORUYUCU ROLÜ

Öz

Amaç: Bu çalışmanın amacı, Wistar sıçanlarında, kronik bakır sülfat zehirlenmesine (100mg / Kg bw) karşı yaygın alıç Crataegus monogyna sulu ekstraktının (1.5g / Kg bw/ gün) olası faydalı kullanımını araştırmaktır.

Gereç ve Yöntem: Hayvanlar, tedavi edilmemiş kontrol (C), sırasıyla alıç meyveleri (F) ve yaprakları (L) ile muamele edilmiş 2 pozitif kontrol, bakır (Cu) ile muamele edilmiş grup ve Cu ve alıç meyveleri (CuF) ve Cu ve alıç yaprakları (CuL) ile muamele edilmiş 2 kombine tedavi grubu olmak üzere 6 gruba ayrılmıştır. 30 günlük oral uygulamadan sonra, epididimal sperm konsantrasyonu, motilite, canlılık, hız (VCL, VSL ve VAP), dış yana baş deplasmanının amplitüdü (ALH) ve sperm kuyruğu vuruş sıklığının (BCF) yanısıra testis ağırlığı ve plazma testosteron seviyeleri değerlendirilmiştir. Ayrıca, testis glutatyonu (GSH), malondialdehid (MDA) ve glutatyonperoksidaz (GPx) da değerlendirilmiştir.

Sonuç ve Tartışma: Cu maruziyeti, kontrol gruplarına kıyasla testosteron, sperm konsantrasyonu, canlı sperm, VCL, VSL, VAP, ALH, BCF, GSH ve GPx seviyelerini azaltmıştır. Cu grubunun sıçanlarında ölü sperm ve MDA seviyeleri, tedavi edilmeyen kontrole kıyasla artmıştır. Cu grubuyla karşılaştırıldığında, testosteron seviyeleri, sperm konsantrasyonu, sperm motilitesi, canlı sperm, VCL, VSL, VAP, ALH, BCF, GSH ve GPx seviyeleri CuF ve CuL gruplarında çok daha yüksek ve MDA konsantrasyonları ise anlamlı olarak düşüktür. Sonuç olarak, alıç, Cu ile sulu bir özüt olarak uygulandığında, bakır toksisitesine karşı çoğu biyolojik belirteci korumuş ve sperm konsantrasyonunu ve hızını (VCL ve VAP) artırmıştır

Anahtar Kelimeler

• Bakır
• C. monogyna
• CASA
• sperm
• testosteron

PROTECTIVE ROLE OF CRATAEGUS MONOGYNA ON SPERM QUALITY AND TESTIS OXIDATIVE STRESS AGAINST COPPER-INDUCED TOXICITY

Öz

Objective: The purpose of this study was to investigate the possible beneficial use of common hawthorn Crataegus monogyna aqueous extract at 1.5g/Kg bw/day against chronic copper sulfate intoxication (100mg/Kg bw) in Wistar rats.

Material and Method: Animals were divided into 6 groups; the untreated control (C), 2 positive controls treated respectively with hawthorn fruits (F) and leaves (L), 1 group treated with copper (Cu) and 2 combined treatment groups treated with Cu and hawthorn-fruits (CuF) and Cu and hawthorn-leaves (CuL). After 30 days of oral administration, testis weight and plasma testosterone levels were evaluated, in addition to the epididymal sperm concentration, motility, vitality, velocity (VCL, VSL and VAP), the amplitude of lateral head displacement (ALH), and the beat cross frequency (BCF). Testicular glutathione (GSH), malondialdehyde (MDA), and glutathione peroxidase (GPx) were also evaluated.

Result and Discussion: Cu exposure reduced testosterone, sperm concentration, live sperm, VCL, VSL, VAP, ALH, BCF, GSH, and GPx levels compared to control groups. Dead sperm and MDA levels were increased in rats of Cu group compared to the untreated control. When compared to the Cu group, levels of testosterone, sperm concentration, sperm motility, live sperm, VCL, VSL, VAP, ALH, BCF, GSH, and GPx were much higher in the CuF and CuL groups, along with a significantly lower MDA concentration. In conclusion, hawthorn, when co-administered as an aqueous extract with Cu, protected most biological markers against copper toxicit, while positive control (s) boosted sperm concentration and velocity (VCL and VAP).

Anahtar Kelimeler

• C. monogyna
• CASA
• Copper
• sperm
• testosterone

Kaynakça

1. 1. Badiye, A., Kapoor, N., Khajuria, H. (2013). Copper Toxicity: A Comprehensive Study. Research Journal of Recent Sciences, 2, 58-67.
2. 2. Sinkovic, A., Strdin, A., Svensek F. (2008). Severe acute copper sulphate poisoning: a case report. ArhHig Rada Toksikol, 59(1), 31-5.
3. 3. Blundell, S., Curtin, J., Fitzgerald, D. (2003). Blue lips, coma and haemolysis. Journal of Paediatrics and Child Health, 39(1), 67-8.
4. 4. Mario, M. (2014). Abnormal Copper Homeostasis: Mechanisms and Roles in Neurodegeneration, Toxics, 2, 327-345.
5. 5. Hagai, L., Niel, J., Anderson, M.A., Jaime, M., Dan, W.D., Irina, M., Rachel, P., Swan, H. (2017). Temporal trends in sperm counts: a systematic review and meta-regression analysis. Human reproduction updates, 23(6), 646-659. 6. Bamidele, R., Pelumi, O. (2017). Childlessness and Its Socio-Cultural Implication on Married Couples within Some Selected Yoruba Communities in South-West Nigeria. International Journal of Innovative Social Sciences & Humanities Research, 5(1), 42-54.
6. 7. Chen, L., Shi, G.R., Huang, D.D., Li, Y., Ma, C.C., Shia, M., Su, B.X., Shi, G.J. (2019). Male sexual dysfunction: A review of literature on its pathological mechanisms, potential risk factors, and herbal drug intervention. Biomedicine and Pharmacotherapy, 112, 108-585.
7. 8. Duruibe, J., Ogwuegbu, M.O.C., Egwurugwu, J. (2007). Heavy Metal Pollution and Human Biotoxic Effects. International journal of physical sciences, 2(5), 112–118.
8. 9. Swan, H.S., Elkin, E.P., Fenster, L. (2000). The question of declining sperm density revisited: an analysis of 101 studies published 1934–1996. Environmental Health Perspectives, 108(10), 961–966.

9. 10. Liu, J.Y., Yang, X.F., Sun, X., Zhuang, C., Xu, F., Li, Y. (2016). Suppressive Effects of Copper Sulfate Accumulation on the Spermatogenesis of Rats. Biological Trace Element Research, 174, 356–361.
10. 11. Wong, W.Y., Flik, G., Groenen, P.M.W., Swinkels, D.W., Thomas, C.M.G., Copius-Peereboom, J.H.J., Merkus, H.M.W.M., Steegers-Theunissen, R.P.M. ( 2001). The impact of calcium, magnesium, zinc, and copper in blood and seminal plasma on semen parameters in men. Reproductive Toxicology, 15, 131–136.
11. 12. Moriwaki, H., Osborne, M.R., Phillips, D.H.. (2008). Effect of mixing metal ions on oxidative DNA damage mediated by a Fentom-type reduction. Toxicology in Vitro, 22(1), 36-44.
12. 13. Eidi, M., Eidi, A., Pouyan, O., Shahmohammadi, P., Fazaeli, R., Bahar, M. (2011). Seminal plasma levels of copper and its relationship with seminal parameters. Iranian Journal of Reproductive Medicine, 8(2), 60-65.
13. 14. JibrinBala, Y., Meriçli, A.H. (2016). Pharmacological activities of Crataegus species: A review. International Journal of Multidisciplinary Research and Development, 3, 73-76.
14. 15. Fong, H.H., Bauman, J.L. (2002). Hawthorn. Journal of Cardiovascular Nursing, 16, 1–8.
15. 16. Rice-Evans, C. (2004). Flavonoids and isoflavones: absorption, metabolism, and bioactivity. Free Radical Biology and Medicine, 36(7), 827-8.
16. 17. Jeyendran, R.S., Vander-Van, H.H., Perez-Peleaz, M., Crabo, B.G., Zanevld, L.J.D. (1984). Development of an assay to assess the functional integrity of the human sperm membrane and its relationship to other semen characters. Journal of reproducion and fertility, 70(1), 219-228.
17. 18. Weckbercker, G., Cory, J.G. (1988). Ribonucleotide reductase activity and growth of glutathione depended mouse leukaemia L 1210 cells in vitro. Cancer Letters, 40, 257-264. 19. Bradford, M.M. (1976). Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding. Analytical Biochemistry, 72, 248-254.
18. 20. Ohkawa, H., Ohishi, N., Yagi, K. (1979). Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95, 351-358.
19. 21. Flohe, L., Gunzler, W.A. (1984). Analysis of glutathione peroxidase. Methods of Enzymology, 105, 114-121.
20. 22. Chattopadhyay, A., Sarkar, M., Biswas, N.M. (2005). Dose-dependent effect of copper chloride on male reproductive function in immature rats. Kathmandu University Medical Journal, 3(4), 392-400.
21. 23. Mandil, R., Rahal, A., Parkash, A., Gangwar, S.K. (2016). Ameliorative potential of αtocophenol against flubendiamide and copper-induced testicular-insult in wistar rats. Chemico-bioloical interactions, 260, 91-101.
22. 24. Chang, CS., Choi, J.B., Kim, H.J., Park, S.B. (2011). Correlation between serum testosterone level and concentration of copper and zink in hair tissue. Bioloical Trace Element Research, 144(1-3), 264-271.
23. 25. Bedwal, R.S., Bahuguna, A. (1994). Zinc, copper and selenium in reproduction. Experientia, 50(7), 626–40.
24. 26. Wiebe, J.P., Salhanick, A.I., Myer, K.I. (1983). On the mechanism of action of lead in the testis: in vitro suppression of FSH receptors, cyclic AMP and steroidogenesis. Life Science, 32(17), 1997-2005.
25. 27. Krumschnabel, G., Manzal, C., Berger, C., Hofer, B. (2005). Oxidative stress, mitochondiral permeability transition, and cell death in Cu-exposed trout hepatocytes. ToxicalToxicology and Applied Pharmacology, 209(1), 62-73.
26. 28. Knazicka, Z., Tvrda, E., Bardos, L., Lukac, N. (2012). Dose- and time- dependent effect of copper ions on the viability of bull spermatozoa in different media. Journal of Environmental Science and Health Part A Toxic/Hazardous Substances and Environmental Engineering, 47(9), 1294-300. 9. Zhou, J., Chen, L., Li, J., Li, H., Hong, Z., Xie, M., Chen, S., Yao, B. (2015). The Semen pH Affects Sperm Motility and Capacitation. PLoS ONE, 10(7), e0132974.
27. 30. Jimenez, T., Sanchez, G., Wertheimer, E.V., Blanco, G. (2010). Activity of the Na,K-ATPase alpha4 isoform is impor- tant for membrane potential, intracellular Ca2+, and pH to maintain motility in rat spermatozoa. Reproduction, 139(5), 835–45. 31. Olivari, F.A., Hernẚndez, P.P., Allende, M.L. (2008). Acute copper exposure induces oxidative stress and cell death in lateral line hair cells of zebrafish larvea. Brain research, 1244, 1-12.
28. 32. Sadek, A.S., Abd El Shakour, A., Zaki A., Ibrahim, A.M., Mahmoud, I.S., Mostafa, T.B., (2011). Sperm chromatin condensation in infertile men with varicocele before and after surgical repair. Fertility and sterility, 95(5), 1705-8.
29. 33. Dupont, C.L., Grass, G., Rensing, C. (2011). Copper toxicity and the origin of bacterial resistance-new insights and applications. Metallomics, 3(11), 1109–1118.
30. 34. Witting, P.K., Bowry, V.W., Stocker, R. (1995). Inverse deuterium kinetic isotope effect for peroxidation in human low-density lipoprotein (LDL): a simple test for tocopherol- mediated peroxidation of LDL lipids. FEBS Letters, 375(1-2), 45-49.
31. 35. Sevcikova, M., Modra, H., Slaninova, A., Svobodova, Z. (2011). Metals as a cause of oxidative stress in fish: a review. Veterinárnímedicína, 56(11), 537-546.
32. 36. Jiang, W.D., Liu, Y., Kai, H., Jiang, J., Li, S.H., Feng, L., Zhou, X.Q. (2014). Copper exposure induces oxidative injury, disturbs the antioxidant system and changes the Nrf/ARE (CuZnSOD) signaling in the fish brain: protective effect of myo-inositol. Aquatic toxicology, 155C, 301-313.
33. 37. Danyelle, T.M., Kanneth, T.D. (2003). The role of glutathion S-transferase in anti-cancer drug resistance. Oncogene, 22(47), 7369-75.
34. 38. Miller, A.L. (1998). Botanical influences on cardiovascular disease. Alternative Medicine Review, 3, 422-431.
35. 39. Ju, L.Y. (2005). Crataegus oxyacantha (aubepine) in the use as herb medicine in France. Zhongguo Zhong Yao ZaZhi, 30(8), 634-40.
36. 40. Rosario, G.M., Emmanuel, I.E., Raúl, N.A. (2013). Antioxidant compounds in hawthorn fruits (Crataegus spp.) of Mexico. Revista Mexicana de Biodiversidad, 84(4), 1298-1304.
37. 41. Yousef, M.I., Abdullah, G.A., Kamel, I. (2003). Effect of ascorbic acid and vitamin E supplementation on semen quality and biochemical parameters of male rabbits. Animal Reproduction Science, 76(1-2), 99-111.
38. 42. Agarwal, A., Nallella, K.P., Allamaneni, S.S. (2004). Said TM. Role of antioxidants in treatment of male infertility: an overview of the literature. Reproductive biomedicine online, 8(6), 616-27.
39. 43. Frieden, E. (1986). Perspectives on copper biochemistry. Clinical physiology and biochemistry, 4(1), 11-9.
40. 44. Hu, L., Xiong, C.L. (2006). The influence of medicated serum with root of Crataegus cuneata on human sperm motility parameters in vitro. Zhongguo Zhong Yao ZaZhi. 31(4), 333-5. 45. Keser, S., Celik, S., Turkoglu, S., Yilmaa, Ö., Turkoglu, I. (2015). Vitamin, Sterol and Fatty Acid Contents of Some Edible and Medicinal Plants from East and Southeast Anatolia (Turkey). Turkish Journal of Pharmaceutical Sciences, 12(2), 46-59.
41. 46. Bechkri, S., Berrehal, D., Semra, Z., Bachari, K., Kabouche, A., Kabouche, Z. (2017). Composition and biological activities of seeds oils of two Crataegus species growing in Algeria. . Journal of Materials and Environmental Sciences, 8(3), 1023-1028.
42. 47. Froehlicher, T., Hennebelle, T., Martin-Nizard, F., Cleenewerck, P., Hilbert, J.L., Trotin, F., Grec, S. (2009). Phenolic profiles and antioxidative effect of hawthorn cell suspension, fresh fruits, and medicinal dried parts. Food Chemistry, 115(3), 897-903.
43. 48. Masteikova, R., Muselik, J., Bernatonienė, J., Bernatonienė, R. (2007). Antioxidative activity of Ginkgo, Echinacea, and Ginseng tinctures. Medicina (Kaunas), 43(4), 306-9.
44. 49. Liu, T., Cao, Y., Zhao, M. (2010). Extraction optimization, purification and antioxidant activity of procyanidins from hawthorn (C. pinnatifida Bge. var. major) fruits. Food Chemistry, 119(4), 1656-1662.
45. 50. Hwang, K. and Dolores J.b. (2013). Molecular mechanisms of antioxidants in male infertility. In: S.J. Parekattil and A. Agarwal (eds.), Antioxidants in male infertility: A guide for clinicians and researchers, (pp 93). New York Heidelberg Dordrecht London: springer.
46. 51. Putri, N.D., Lipoeto, N.I., Reza, M. (2018). Effects of Omega 3 on Testosterone Hormone Levels and Quality of Spermatozoa in Obese Rattus Norvegicus Wistar Albino Strai. International Biological and Biomedical Journal Summer, 4(3), 156-163.
47. 52. Kanadaswami, C., Lee, L.T., Lee, P.P.H., Hwang, J.J., Ke, F.C., Huang, Y.T., Lee, M.T. (2005). The antitumor activities of flavonoids. In vivo, 19(5), 895-909.
48. 53. Seddiki, Y., Helena, M., Fernando, M. (2017). Antioxidant Properties of Polyphenols and Their Potential Use in Improvement of Male Fertility: A Review. Biomedical journal of scientific and technical research, 1(3), 2574-1241.
49. 54. Zribi, N., Chakroun, FN., Ben Abdallah, F., Elleuch, H., Sellami, A., Jalel, G., Rebai, T., Fakhfakh, F., Ammar-Keskes, L. (2012). Effect of freezing-thawing process and quercetin on human sperm survival and DNA integrity. Cryobiology, 65(3), 326-331.
50. 55. Taepongsorat, L., Tangpraprutgul, P., Noppadon, K., Malaivijitnond, S. (2008). Stimulating effects of quercetin on sperm quality and reproductive organs in adult male rats, Asian Journal of Androloy, 10(2), 249–258.
51. 56. Nabavi, S.F., Habtemariam, S., Touqeer, A., Antoni, S., Daglia, M., Eduardo, S., Nabavi, S.M. (2015). Polyphenolic Composition of Crataegus monogyna Jacq: From Chemistry to Medical Applications. Nutrients, 7, 7708-7728. 57. Sajid, U., Yingying, H., Lei, Z., Shibin, F., Ibrar, M.K., Jinjie, W., Yu, L., Xichun, W. (2018). Therapeutic Role of Green Tea Polyphenols in Improving Fertility: A Review. Nutrients, 10(7), 834.