Serkan YILDIRIM, Fatih Çağlar ÇELİKEZEN, Saadet BELHAN, Gökhan OTO, Gizem ESER, Emin ŞENGÜL, Dursunali ÇINAR

Investigation of protective effects of lithium borate on spermatogenesis and testes histopathology against cadmium-induced acute toxicity in rats

In this study, protective effects of lithium borate LTB on spermatogenesis as well as histopathological and immunohistochemical findings of testes in experimentally induced acute Cadmium Cd toxicity in rats were determined. Twenty-eight male Wistar albino rats, were used, weighing 200-220 g. Rats were randomly divided into 4 groups: Control, Cd, LTB, and LTB + Cd. Rats were anesthetized with ketamine at the end of the sixth day, blood was taken from their hearts, and the rats were decapitated. Typically, the control and LTB groups exhibited similar values. Compared with those observed for the control group, the sperm morphology i.e. abnormal sperm count increased for the Cd group, while the FSH, LH, total testosterone levels, sperm motility, and density decreased in a statistically significant manner. Clearly, no adverse effects of LTB on the sperm motility, density, and sperm morphology i.e. abnormal sperm count were observed, but LTB decreased the negative effects of Cd toxicity. Abnormal disturbances in the head and tail areas of the sperms increased; thus, the total abnormal sperm rate increases, leading to the decreased fertilization capacity. The histopathological examination of testicular tissues revealed severe haemorrhage and hyperaemia in intertubular intervals, tubule atrophy, severe degenerative and necrotic changes in spermatocytes, tubule wall thinning, and necrosis in basal germ cells. In immunohistochemically Caspase-3, 8-OHdG, and COX-2 staining, changes in the control and LTB groups were not detected, while the Cd toxicity group exhibited severe expression in the testis tissue. Histopathological and immunohistochemical changes were significantly decreased in the LTB + Cd group compared to the Cd group. In conclusion, in this study it was determined that LTB has protective effects on Cd-induced testicular toxicity in rats.

Keywords:

Acute cadmium toxicity, hormones, spermatogenesis, histopathological findings, lithium borate, rat,

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Acharya UR, Mishra M, Patro J, Panda MK (2008). Effect of vitamins C and E on spermatogenesis in mice exposed to cadmium. Reproductive Toxicology 25: 84-88. doi: 10.1016/j. reprotox.2007.10.004
Akinloye O, Arowojolu AO, Shittu OB, Anetor JI (2006). Cadmium toxicity: a possible cause of male infertility in Nigeria. Reproductive Biology 6: 17-30.
Baldwin DR, Marshall WJ (1999). Heavy metal poisoning and it’s laboratory Investigation. Annals of Clinical Biochemistry 36: 267-300. doi: 10.1177/000456329903600301
Barranco WT, Kim DH, Stella Jr-SL, Eckhert CD (2009). Boric acid inhibits stored Ca (2+) release in DU - 145 prostate cancer cells. Cell Biology and Toxicology 25: 309-320. doi: 10.1007/ s10565 - 008 - 9085 - 7
Becker K, Müssig - Zufika M, Hoffmann K, Krause C, Meyer E et al. (1997). Umwelt - survey 1990/92 band V: Trinkwasser.
Deskription der Spurenelementgehalte im Haushaltsund Wasserwerks Trinkwasser der Bevölkerung in der Bundesrepublik Deutschland. Berlin, Germany: Institute for Water, Soil and Air Hygiene of the Federal Environmental Agency (in German).
Belhan S, Özkaraca M, Kandemir FM, Yildirim S, Gülyüz F et al. (2017). Ratlarda metoraksat kaynaklı testiküler toksisite üzerine hesperidinin etkisi. Kafkas Üniversitesi Veteriner Fakultesi Dergisi 23: 789-796. doi: 10.9775/kvfd.2017.17752
Belhan S, Çomaklı S, Küçükler S, Gülyüz, F, Yıldırım S et al. (2019). Effect of chrysin on methotrexate‐induced testicular damage in rats. Andrologia 51: e13145. doi: 10.1111/and.13145
Bernhoft RA (2013). Cadmium toxicity and treatment. The Scientific World Journal 2013: 394652. doi: 10.1155/2013/394652
Bustos - Obregón E, Poblete D, Catriao R, Fernandes FH (2013). Protective role of melatonin in mouse spermatogenesis induced by sodium arsenite. International Journal of Morphology 27: 849-856. doi:10.4067/S0717 - 95022013000300012
Cannino G, Ferruggıa E, Luparello C, Rinaldi AM (2009). Cadmium and mitochondria. Mitochondrion 9: 377-384. doi: 10.1016/j. mito.2009.08.009
Celikezen FÇ, Turkez H., Başak T, İzgi MS (2014). DNA damaging and biochemical effects of potassium tetraborate. Experimental and Clinical Sciences Journal 13: 446-450.
De Souza Predes F, Diamante MAS, Foglio MA, Dolder H (2016). Effects of Arctium lappa on cadmium - induced damage to the testes and epididymis of adult wistar rats. Biological Trace Element Research 173: 362-371. doi: 10.1007/s12011 - 016 - 0663 - x
Devirian TA, Volpe SL (2003). The physiological effects of dietary boron. Critical Reviews in Food Science and Nutrition 43: 219-231. doi: 10.1080/10408690390826491
Dixon RL, Lee IP, Sherins RJ (1976). Methods to assess reproductive effects of environmental chemicals: studies of cadmium and boron administered orally. Environmental Health Perspectives 13: 59-67. doi: 10.1289/ehp.761359
Gökalp O, Özer MK, Koyu A, Çiçek E, Sütçü R et al. (2005). Ratlarda kadmiyumun pankreasa etkileri. SDÜ Tıp Fakültesi Dergisi 12: 27-30.
Gupta RK, Barnes GW, Skelton FR (1967). Light microscopic and immunopathologic observations on cadmium chloride induced injury in the mature rat testes. The American Journal of Pathology 51: 191-204.
Himeno S, Aoshima K (2019). Cadmium Toxicity: New Aspects in Human Disease, Rice Contamination, and Cytotoxicity. New York, NY, USA: Springer.
Joe MH, Sun WJ, Seong H, Sang YL, Hyun PS et al (2011). Genomewide response of Deinococcus radiodurans on cadmium toxicity. Microbiol Biotechnol 21: 438-447.
Kay J, Thomas DG, Brown MW, Cryer A, Shurben D et al. (1986) Cadmium accumulation and protein binding patterns in tissues of rainbow trout, Salmo Gairdneri. Environmental Health Perspectives 65: 133-139. doi: 10.1289/ehp.8665133
Kim DH, Que Hee S, Norris A, Faull KF, Eckhert CD (2006). Boric acid inhibits ADP - ribosyl cyclase non - competitively. Journal of Chromatography A 1115: 246-252 doi: 10.1016/j. chroma.2006.02.066
Liu X, Jia Y, Chong L, Jiang J, Yang Y et al. (2018). Effects of oral cimetidine on the reproductive system of male rats. Experimental and Therapeutic Medicine 15: 4643- 4650. doi: 10.3892/etm.2018.6065
Marcano LBC, Carruyo IM, Montiel XM, Morales CB, Soto PM (2009). Effect of cadmium on cellular viability in two species of microalgae (Scenedesmus sp. and Dunaliella viridis). Biological Trace Element Research 130: 86-93. doi: 10.1007/s12011 - 009 - 8316 - y
Mason K, Brown J, Young J, Nesbit R (1964). Cadmium - induced injury of the rat testes. The Anatomical Record 149: 135-148.
Meeker JD, Rossano MG, Protas B, Diamond MP, Puscheck E et al. (2008). Cadmium, lead, and other metals in relation to semen quality: human evidence for molybdenum as a male reproductive toxicant. Environmental Health Perspectives 116: 1473-1479. doi: 10.1289/ehp.11490
Méndez - Armenta M, Rios C (2007). Cadmium neurotoxicity. Environmental Toxicology and Pharmacology 23: 350-358. doi: 10.1016/j.etap.2006.11.009
Modi V, Akst S, Davison D (2019). 1715: Acute cadmium toxicity causing multisystem organ failure. Critical Care Medicine 47(1): 831. doi: 10.22088/cjim.8.3.135
Moore JA (1997). Expert scientific committee, an assessment of boric acid and borax using the IEHR evaluative process for assessing human developmental and reproductive toxicity of agents. Reproductive Toxicology 11: 123-160.
Naghii MR, Saman S (1996). The effect of boron supplementation on the distribution of boron in selected tissues and on testosterone synthesis in rats. The Journal of Nutritional Biochemistry 7: 507-512. doi: 10.1007/BF02785299
Oto G, Yildirim S, Dede S, Ozdemir H, Yener Z et al. (2017). Therapeutic potential of boric acid and borax: dietary approaches for cancer prevention. Fresenius Environmental Bulletin 26: 2260-2268.
Rahim F, Jalali A, Tangestani R (2013). Breast cancer frequency and exposure to cadmium: a meta - analysis and systematic review. Asian Pacific Journal of Cancer Prevention 14: 4283- 4287. doi: 10.7314/apjcp.2013.14.7.4283
Saripinar Aksu D, Saglam YS, Yildirim S, Aksu T (2017). Effect of pomegranate (Punica granatum L.) juice on kidney, liver, heart, and testes histopathological changes, and the tissues lipid peroxidation and antioxidant status in lead acetate - treated rats. Cellular and Molecular Biology 63: 33-42. doi: 10.14715/ cmb/2017.63.10.5
Sarkar A, Ravindran G, Krishnamurthy V (2013). A brief review on the effect of cadmium toxicity: from cellular to organ level. International Journal of Advanced Biotechnology and Research 3: 17-36. doi: 10.1177/1179561117726090
Schwartz GG, Reis IM (2000). Is cadmium a cause of human pancreatic cancer? Cancer Epidemiology, Biomarkers & Prevention 9: 139-145.
Sonmez M, Türk G, Yüce A (2005). The effect of ascorbic acid supplementation on sperm quality, lipid peroxidation and testosterone levels of male Wistar rats. Theriogenology 63: 2063-2072. doi: 10.1016/j.theriogenology.2004.10.003
Thompson J, Bannıgan J (2008) Cadmium: Toxic Effects on the Reproductive System and the Embryo. Reproductive Toxicology 25: 304-315. doi: 10.1016/j.reprotox.2008.02.001
Turk G, Sönmez M, Aydin M, Yüce A, Gür S et al. (2008). Effects of pomegranate juice consumption on sperm quality, spermatogenic cell density, antioxidant activity and testosterone level in male rats. Clinical Nutrition 27: 289-296. doi: 10.1016/j.clnu.2007.12.006
Türkez H, Geyikoglu F, Tatar A, Keles MS, Kaplan I (2012) The effects of some boron compounds against heavy metal toxicity in human blood. Experimental and Toxicologic Pathology 64: 93-101. doi: 10.1016/j.etp.2010.06.011
Usuda K, Koichi K, Orita Y, Dote T, Iguchi K et al. (1998) Serum andurinary boronlevels in rats after single administration of sodium tetraborate. Archives of Toxicology 72: 468 - 474.
Weir Jr RJ, Fisher RS (1972). Toxicologic studies on borax and boric acid. Toxicology and Applied Pharmacology 23: 351-364. doi: 10.1016/0041 - 008x(72)90037 - 3
Yang HS, Han DK, Kim JR, Sim JC (2006). Effects of alpha - tocopherol on cadmium - induced toxicity in rat testes and spermatogenesis. Journal of Korean Medical Science 21: 445- 451. doi: 10.3346/jkms.2006.21.3.445
Yari A, Asadi MH, Bahadoran H, Dashtnavard H, Imani Het al. (2010). Cadmium Toxicity in Spermatogenesis and Protective Effects of L - Carnitine in Adult Male Rats. Biological Trace Element Research 137: 216-225. doi: 10.1007/s12011 - 009 - 8577 - 5
Yildirim S, Belhan S, Uyar H, Huyut Z, Oto G et al. (2018a). Kronik Olarak Flor ve 7, 12 - Dimetilbenzantrasene (DMBA) Maruz Kalmanın Ratlarda Spermatogenezis ve Testisin Histopatolojisine Etkileri. Atatürk Üniversitesi Veteriner Bilimleri Dergisi 13: 141-148. doi: 10.17094/ataunivbd.345511
Yildirim S, Celikezen FC, Oto G, Sengul E, Bulduk M et al. (2018b). An investigation of protective effects of litium borate on blood and histopathological parameters in acute cadmium - induced rats. Biological Trace Element Research 182: 287-294. doi: 10.1007/s12011 - 017 - 1089 - 9