Published date: Aug 19 2020

Journal Title: International Journal of Reproductive BioMedicine

Issue title: International Journal of Reproductive BioMedicine (IJRM): Volume 18, Issue No. 8

Pages: 611–624

DOI: 10.18502/ijrm.v13i8.7503

Babatunde Ogunladebogunlade@futa.edu.ngDepartment of Human Anatomy, Federal University of Technology, Akure, Ondo State, Nigeria

Sunday AdelakunDepartment of Human Anatomy, Federal University of Technology, Akure, Ondo State, Nigeria

Kingsley IteireDepartment of Human Anatomy, University of Medical Sciences, Ondo city, Ondo State, Nigeria

Background: The exposure of male individual to environmental toxicant is regarded as a channel that results in reduced sperm counts and infertility.

Objective: This study investigated the ameliorative response of Sulforaphane (SFN) on Aluminum trichloride (AlCl3) induced testicular toxicity in adult male Wistar rats.

Materials and Methods: A total of 32 adult male Wistar rats (180-200 gm between 8-10 wk) were divided into four groups (n = 8/each). Group A) received distilled water orally as placebo; Group B) received 100 mg/kgbw AlCl3 only orally; Group C) received 100 mg/kgbw AlCl3 and 100 mg/kgbw SFN orally; and Group D) received 100 mg/kgbw SFN only orally. After 28 days of experiment, animals underwent cervical dislocation, blood serum was obtained for analysis, and testes were harvested for biochemical assays, histology, hormonal profile, and sperm characterization.

Results: The sperm parameters showed a significant difference within the AlCl3 only group compared with the control and SFN only groups (p = 0.02). However, AlCl3 and SFN co-treatment showed improvement in the motility, viability, and sperm count compared with the AlCl3 only group (p = 0.02). Furthermore, there was a significant decline in the levels of hormones profile and antioxidant status in AlCl3 only group compared to the control and SFN only (p = 0.02). The testicular histoarchitecture of the AlCl3 only group showed shrinkage of seminiferous tubules, spermatogenesis disruption, and empty lumen compared to the control and SFN only groups.

Conclusion: The present study revealed the ameliorative response of SFN on AlCl3-induced testicular toxicity on serum hormone profiles, antioxidant status, lipid peroxidation, and histomorphometric analysis through oxidative stress.

Key words: Sulforaphane, Aluminum trichloride, Oxidative stress, Testis, Histology.

[1] Nordkap L, Joensen UN, Blomberg Jensen M, Jørgensen N. Regional differences and temporal trends in male reproductive health disorders: semen quality may be a sensitive marker of environmental exposures. Mol Cell Endocrinol 2012; 355: 221–230.

[2] Mehrpour O, Karrari P, Zamani N, Tsatsakis AM, Abdollahi M. Occupational expxosure to pesticides and consequences on male semen and fertility: A review. Toxicol Lett 2014; 230: 146–156.

[3] Verstraeten SV, Aimo L, Oteiza PI. Aluminum and lead: Molecular mechanism of brain toxicity. Arch Toxicol 2008; 82: 789–802.

[4] Venturini-Soriano M, Berthon G. Aluminum speciation studies in biological fluids. Part 7. A quantitative investigation of aluminum (III)-malate complexequilibria and their potential implications for aluminum metabolism and toxicity. J Inorg Biochem 2001; 85: 143–154.

[5] Yousef MI, Salama AF. Propolis protection from reproductive toxicity caused by aluminium chloride in male rats. Food Chem Toxicol 2009; 47: 1168–1175.

[6] Choi EJ. Antioxidative effects of hesperetin against 7, 12- dimethylbenz (a) anthracene-induced oxidative stress in mice. Life Sci 2008; 82: 1059–1064.

[7] Gurjar M, Baronia AK, Azim A, Sharma K. Managing aluminum phosphide poisonings. J Emerg Trauma Shock 2011; 4: 378–384.

[8] Hirata A, Murakami Y, Shoji M, Kadoma Y, Fujisawa S. Kinetics of radical-Scavenging activity of hesperetin and hesperidin and their inhibitory activity on COX-2 expression. Anticancer Res 2005; 25: 3367–3374.

[9] Anand R, Kumari P, Kaushal A, Bal A, Wani WY, Sunkaria A, et al. Effect of acute aluminum phosphide exposure on rats- A biochemical and histological correlation. Toxicol Lett 2012; 215: 62–69.

[10] Zhao Z, Liao G, Zhao Q, Lv D, Holthfer H, Zou H. Sulforaphane attenuates contrast-induced nephropathy in rats via Nrf2/HO-1 pathway. Oxid Med Cell Longev 2016; 8: 25–32.

[11] Lee JH, Moon MH, Jeong JK, Park YG, Lee YJ, Seol JW, et al. Sulforaphane induced adipolysis via hormone sensitive lipase activation, regulated by AMPK signaling pathway. Biochem Biophys Res Commun 2012; 426: 492–497.

[12] Choi KM, Lee YS, Kim W, Kim SJ, Shin KO, Yu JY, et al. Sulforaphane attenuates obesity by inhibiting adipogenesis and activating the AMPK pathway in obese mice. J Nutr Biochem 2014; 25: 201–207.

[13] Bahadoran Z, Tobidi M, Nazeri P, Mehran M, Azizi F, Mirmiran P. Effect of broccoli sprouts on insulin resistance in type 2 diabetic patients: a randomized double-blind clinical trial. Int J Food Sci Nutr 2012; 63: 767–771.

[14] De Souza CG, Sattler JA, de Assis AM, Rech A, Santos Perry ML, Souza DO. Metabolic effects of sulforaphane oral treatment in streptozotocindiabetic rats. J Med Food 2012; 15: 795–801.

[15] Bai Y, Cui W, Xin Y, Miao X, Barati MT, Zhang C, et al. Prevention by sulforaphane of diabetic cardiomyopathy is associated with upregulation of Nrf2 expression and transcription activation. J Mol Cel Cardiol 2013; 57: 82–95.

[16] Shan Y, Zhao R, Geng W, Lin N, Wang X, Du X, et al. Protective effect of sulforaphane on human vascular endothelial cells against lipopolysaccharideinduced inflammatory damage. Cardiovascular Toxicology 2010; 10: 139–145.

[17] Kensler TW, Chen JG, Egner PA, Fahey JW, Jacobson LP, Stephenson KK, et al. Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin- DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo township, qidong, people’s republic of China. Cancer Epidemiol Biomarkers Prev 2005; 14: 2605–2613.

[18] Ushida Y, Talalay P. Sulforaphane accelerates acetaldehyde metabolism by inducing aldehyde dehydrogenases: Relevance to ethanol intolerance. Alcohol and Alcoholism 2013; 48: 526–534.

[19] Toyama T, Shinkai Y, Yasutake A, Uchida K, Yamamoto M, Kumagai Y. Isothiocyanates reduce mercury accumulation via an Nrf2- dependent mechanism during exposure of mice to methylmercury. Environ Health Perspect 2011; 119: 1117–1122.

[20] Egner PA, Chen JG, Zarth AT, Ng DK, Wang JB, Kensler KH, et al. Rapid and sustainable detoxication of airborne pollutants by broccoli sprout beverage: Results of a randomized clinical trial in China. Cancer Prev Res 2014; 7: 813–823.

[21] Kensler TW, Egner PA, Agyeman AS, Visvanathan K, Groopman JD, Chen JG, et al. Keap1-nrf2 Signaling: A target for cancer prevention by sulforaphane. Top Curr Chem 2013; 329: 163–177.

[22] Gaona-Gaona L, Molina-Jijón E, Tapia E, Zazueta C, Hernández-Pando R, Calderón-Oliver M, et al. Protective effect of sulforaphane pretreatment against cisplatin-induced liver and mitochondrial oxidant damage in rats. Toxicology 2011; 286: 20–27.

[23] Talalay P, Fahey JW, Healy ZR, Wehage SL, Benedict AL, Min C, et al. Sulforaphane mobilizes cellular defenses that protect skin against damage by UV radiation. Proc Nati Acad Sci USA 2007; 104: 17500– 17505.

[24] Singh K, Connors SL, Macklin EA, Smith KD, Fahey JW, Talalay P, et al. Sulforaphane treatment of autism spectrum disorder (ASD). Proc Natl Acad Sci USA 2014; 111: 15550–15555.

[25] Yanaka A, Fahey JW, Fukumoto A, Nakayama M, Inoue S, Zhang S, et al. Dietary sulforaphane-rich broccoli sprouts reduce colonization and attenuate gastritis in helicobacter pylori-infected mice and humans. Cancer Prev Res 2009; 2: 353–360.

[26] Kikuchi M, Ushida Y, Shiozawa H, Umeda R, Tsuruya K, Aoki Y, et al. Sulforaphane-rich broccoli sprout extract improves hepatic abnormalities in male subjects. World J Gastroenterol 2015; 21: 12457– 12467.

[27] Zhang Y, Tang L. Discovery and development of sulforaphane as a cancer chemopreventive phytochemical. Acta Pharmacol Sin 2007; 28: 1343– 1354.

[28] Avwioro OG. Histology and tissue pathology. Principles and techniques. 2nd ed. Ibadan: Claverianum Press; 2010.

[29] Feng R, He W, Ochi H. A new murine oxidative stress model associated with senescence. Mech Ageing Dev 2001; 122: 547–559.

[30] World Health Organization. WHO laboratory manual for the examination of human semen and semencervical mucus interaction. 4th ed. Cambridge: University Press; 1999.

[31] Adelakun SA, Ukwenya VO, Ogunlade BS, Aniah JA, Ibiayo AG. Nitrite-induced testicular toxicity in rats: therapeutic potential of walnut oil. JBRA Assist Reprod 2019; 23: 15–23.

[32] Akang EN, Oremosu AA, Osinubi AA, Dosumu OO, Kusemiju TO, Adelakun SA, et al. Histomorphometric studies of the effects of Telfairiaoccidentalis on alcohol-induced gonado-toxicity in male rats. Toxicol Rep 2015; 2: 968–975.

[33] Howard CV, Reed MG. Unbiased stereology: Threedimensional measurement in microscopy. 2nd Ed. Abingdon: Garland Science/BIOS Scientific; 2005.

[34] Baines H, Nwagwu MO, Hastie GR, Wiles RA, Mayhew TM, Ebling FJ. Effects of estradiol and FSH on maturation of the testis in the hypogonadal (hpg) mouse. Reprod Biol Endocrinol 2008; 6: 4–13.

[35] Jørgensen N, Vierula M, Jacobsen R, Pukkala E, Perheentupa A, Virtanen HE, et al. Recent adverse trends in semen quality and testis cancer incidence among Finnish men. Int J Androl 2011; 34: e37–e48.

[36] Carlsen E, Giwercman A, Keiding N, Skakkebaek NE, et al. Evidence for decresing quality of semen during past 50 years. BMJ 1992; 305: 609–613.

[37] Geoffroy-Siraudin C, Loundou Ad, Romain F, Achard V, Courbiere B, Perrard MH, et al. Decline of semen quality among 10932 males consulting for couple infertility over a 20-year period in Marseille, France. Asian J Androl 2012; 14: 584–590.

[38] Cheraghi E, Golkar A, Roshanaei K, Alani B. Aluminium-induced oxidative stress, apoptosis and alterations in testicular tissue and sperm quality in wistar rats: Ameliorative effects of curcumin. Int J Fertil Steril 2017; 11: 166–175.

[39] Franca LR, Godinho CL. Testis Morphometry, Seminiferous Epithelium Cycle Length, and Daily Sperm Production in Domestic Cats (Felis catus). Biol Reprod 2003; 68: 1554–1561.

[40] Pandey G, Jain GC. Aluminium chloride-induced testicular effects in rats: A histomorphometrical study. Asian Journal of Applied Science and Technology 2017; 1: 46–52.

[41] Trif A, Muselin F, Argherie D, Dumitrescu E, Măcinic I. The consequences of chronic exposure to aluminium on some morphological biomarkers of reproductive function (body, genital organs, sexual accessory glands weight, seminiferous tubules diameter) in male rats. Lucrări Stiinłifice Medicină Veterinară 2007; 40: 652–658.

[42] Saleh RA, Agarwal A. Oxidative stress and male infertility: from research bench to clinical practice. J Androl 2002; 23: 737–752. [43] Bansal AK, Bilaspuri GS. Impacts of oxidative stress and antioxidants on semen functions. Vet Med Int 2010; 2011: 137–143.

[44] Akinloye O, Arowojolu AO, Shittu OB, Anetor JI. Cadmium toxicity: A possible cause of male infertility in Nigeria. Reprod Biol 2006; 6: 17–30.

[45] Isaac JA, Bolanle AM, Oluyemi A. Modulatory effects of kolaviron (Garcina kola extract) on spermogram and reproductive system of adult male wistar rats in lead acetate induced toxicity. J Toxicol Environ Health Sci 2013; 5: 121–130.

[46] Al-Attar AM. Antioxidant effect of vitamin E treatment on some heavymetals-induced renal and testicular injuries inmale mice. Saudi J Biol Sci 2011; 18: 63– 72.

[47] Guo CH, Lin CY, Yeh MS, Wang Hsu GS. Aluminuminduced suppression of testosterone through nitric oxide production in male mice. Environ Toxicol Pharmacol 2005; 19: 33–40.

[48] Yakubu OE, Nwodo OFC, Imo C, Ogwoni HA. Spermatogenic and haematological effects of aqueous and ethanolic extracts of hymenocardiaacida stem bark on aluminiuminduced toxicity in male wistar rats. Insights in Biomedicine 2017; 2: 1–5.

[49] Nuhair RS. Effects of aluminum chloride on some hormones levele and reproductive organs of male rats (Rattusnorvegicus). University of Thi-Qar Journal of Science 2015; 5: 3–9.

[50] Dobashi M, Fujisawa M, Yamazaki T, Okuda Y, Kanzaki M, Tatsumi N, et al. Inhibition of steroidogenesis in Leydig cells by exogenous nitric oxide occurs independently of steroidogenic acute regulatory protein(star) mRNA. Arch Androl 2001; 47: 203–209.

[51] Dobashi M, Fujisawa M, Yamazaki T, Okuda Y, Kanzaki M, Tatsumi N, et al. Inhibition of steroidogenesis in Leydig cells by exogenous nitric oxide occurs independently of steroidogenic acute regulatory protein (star) mRNA. Arch Androl 2001; 47: 203–209.

[52] Shahraki MR, Zahedi Asl S, Sarkaki AR. The effect of aluminum injection in lateral ventricle on sex hormones in male rat. Shiraz E-Medical Journal 2004; 5: 1–10.

[53] Sikka SC, Rajasekaran M, Hellstorm WJ. Role of oxidative stress and antioxidants in male infertility. J Androl 1995; 16: 464–468.

[54] Rao MV, Gangadharan B. Antioxidative potential of melatonin against mercury induced intoxication in spermatozoa in vitro. Toxicol In Vitro 2008; 22: 935– 942.

[55] Anane R, Creppy EE. Lipid peroxidation as pathway of aluminium cytotoxicity in human skin fibroblast cultures: prevention by superoxide dismutase catalase and vitamins E and C. Hum Exp Toxicol 2001; 20: 477–481.

[56] Turner RMO. Pathogenesis, diagnosis, and management of testicular degeneration in stallions. Clinical Techniques in Equine Practice 2007; 6: 278–284.

[57] Khattab FKI. Histological and ultrastructural studies on the testis of rat after treatment with aluminium chloride. Aust J Basic and Appl Sci 2007; 1: 63–72.

[58] Kang IS, Kim C. Taurine chloramine administered in vivo increases NRF2-regulated antioxidant enzyme expression in murine peritoneal macrophages. Adv Exp Med Biol 2013; 775: 259–267.

[59] Kim C, Cha YN. Taurine chloramine produced from taurine under inflammation provides antiinflammatory and cytoprotective effects. Amino Acids 2014; 46: 89–100.

[60] Kim W, Kim HU, Lee HN, Kim SH, Kim C, Cha YN, et al. Taurine chloramine stimulates efferocytosis through upregulation of Nrf2-Mediated heme oxygenase- 1 expression in murine macrophages: Possible involvement of carbon monoxide. Antioxid Redox Signal 2015; 23: 163–177.

[61] Ahmed YF, Mahmoud GHMK, Farghaly AA, Abo- Zeid MA, Ismail EM. Some studies on the toxic effects of prolonged lead exposure in male rabbits: chromosomal and testicular alterations. Global Veterinaria 2012; 8: 360–366.

[62] Aruldhas MM, Subramanian S, Sekar P, Vengatesh G, Chandrahasan G, Govindarajulu P, et al. Chronic chromium exposure-induced changes in testicular histoarchitecture are associated with oxidative stress: study in a non-human primate (Macaca radiate Geoffroy). Hum Reprod 2005; 20: 2801– 2813.

[63] Pires VC, Gollucke APB, Ribeiro DA, Lungato L, Almeida VD, Aguiar Jr O. Grape juice concentrate protects reproductive parameters of male rats against cadmium-induced damage: A chronic assay. Br J Nutr 2013; 110: 2020–2029.