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Research Article

Effect of Visnagin on Altered Steroidogenesis and Spermatogenesis, and Testicular Injury Induced by the Heavy Metal Lead

Author(s): Jamaan S. Ajarem*, Ahmad K. Hegazy, Gamal A. Allam, Ahmed A. Allam, Saleh N. Maodaa and Ayman M. Mahmoud*

Volume 24, Issue 6, 2021

Published on: 18 September, 2020

Page: [758 - 766] Pages: 9

DOI: 10.2174/1386207323999200918124639

Price: $65

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Abstract

Background: Lead (Pb) is an environmental pollutant causing serious health problems, including impairment of reproduction. Visnagin (VIS) is a furanochromone with promising antioxidant and anti-inflammatory effects; however, its protective efficacy against Pb toxicity has not been investigated.

Objective: This study evaluated the protective effect of VIS on Pb reproductive toxicity, impaired steroidogenesis and spermatogenesis, oxidative stress and inflammation.

Methods: Rats received VIS (30 or 60 mg/kg) and 50 mg/kg lead acetate for 3 weeks and blood and testes samples were collected.

Results: Pb intoxication impaired the pituitary-testicular axis (PTA) manifested by the decreased serum levels of gonadotropins and testosterone. Pb decreased sperm count, motility and viability, increased sperm abnormalities, and downregulated the steroidogenesis markers StAR, CYP17A1, 3β-HSD and 17β-HSD in the testis of rats. VIS significantly increased serum gonadotropins and testosterone, alleviated sperm parameters and upregulated steroidogenesis. In addition, VIS decreased pro-inflammatory cytokines, testicular lipid peroxidation and DNA fragmentation, downregulated Bax, and enhanced antioxidants and Bcl-2.

Conclusion: These results demonstrate the protective effect of VIS against Pb reproductive toxicity in rats. VIS improved serum gonadotropins and testosterone, enhanced steroidogenesis and spermatogenesis, and attenuated oxidative injury, inflammation and apoptosis. Therefore, VIS is a promising candidate for the protection against Pb-induced reproduction impairment.

Keywords: Pituitary-gonadal axis, lead, ROS, coumarins, cytokines, DNA damage, apoptosis.

« Previous Next »
[1]
Organization, W.H. Lead poisoning and health 2019 https://www.who.int/en/news-room/fact-sheets/detail/lead-poisoning-and-health2020.
[2]
Almalki, A.M.; Ajarem, J.; Altoom, N.; Al-Otaibi, F.S.; Maodaa, S.N.; Allam, A.A.; Mahmoud, A.M. Effects of mining activities on Gerbillus nanus in Saudi Arabia: a biochemical and histological study. Animals (Basel), 2019, 9(9), 664.
[http://dx.doi.org/10.3390/ani9090664] [PMID: 31500235]
[3]
Almalki, A.; Ajarem, J.; Allam, A. A.; A El-Serehy, H.; N Maodaa, S.; M Mahmoud, A., Use of Spilopelia senegalensis as a biomonitor of heavy metal contamination from mining activities in Riyadh (Saudi Arabia). Animals (Basel), 2019, 9(12), 1046.
[http://dx.doi.org/10.3390/ani9121046]
[4]
Al-Otaibi, F.S.; Ajarem, J.S.; Abdel-Maksoud, M.A.; Maodaa, S.; Allam, A.A.; Al-Basher, G.I.; Mahmoud, A.M. Stone quarrying induces organ dysfunction and oxidative stress in Meriones libycus. Toxicol. Ind. Health, 2018, 34(10), 679-692.
[http://dx.doi.org/10.1177/0748233718781290] [PMID: 30003843]
[5]
Ghorbe, F.; Boujelbene, M.; Makni-Ayadi, F.; Guermazi, F.; Kammoun, A.; Murat, J.; Croute, F.; Soleilhavoup, J.P.; El-Feki, A. Effect of chronic lead exposure on kidney function in male and female rats: determination of a lead exposure biomarker. Arch. Physiol. Biochem., 2001, 109(5), 457-463.
[http://dx.doi.org/10.1076/apab.109.5.457.8035] [PMID: 11935388]
[6]
Patrick, L. Lead toxicity part II: the role of free radical damage and the use of antioxidants in the pathology and treatment of lead toxicity. Altern. Med. Rev., 2006, 11(2), 114-127.
[PMID: 16813461]
[7]
Kasperczyk, A.; Kasperczyk, S.; Horak, S.; Ostałowska, A.; Grucka-Mamczar, E.; Romuk, E.; Olejek, A.; Birkner, E. Assessment of semen function and lipid peroxidation among lead exposed men. Toxicol. Appl. Pharmacol., 2008, 228(3), 378-384.
[http://dx.doi.org/10.1016/j.taap.2007.12.024] [PMID: 18252257]
[8]
Naha, N.; Bhar, R.B.; Mukherjee, A.; Chowdhury, A.R. Structural alteration of spermatozoa in the persons employed in lead acid battery factory. Indian J. Physiol. Pharmacol., 2005, 49(2), 153-162.
[PMID: 16170983]
[9]
Li, C.; Zhao, K.; Zhang, H.; Liu, L.; Xiong, F.; Wang, K.; Chen, B. Lead exposure reduces sperm quality and DNA integrity in mice. Environ. Toxicol., 2018, 33(5), 594-602.
[http://dx.doi.org/10.1002/tox.22545] [PMID: 29446210]
[10]
Offor, S.J.; Mbagwu, H.O.C.; Orisakwe, O.E. Lack of beneficial effect of activated charcoal in lead induced testicular toxicity in male albino rats. Middle East Fertil. Soc. J., 2017, 22(3), 189-192.
[http://dx.doi.org/10.1016/j.mefs.2017.02.001]
[11]
Anjum, M.R.; Madhu, P.; Reddy, K.P.; Reddy, P.S. The protective effects of zinc in lead-induced testicular and epididymal toxicity in Wistar rats. Toxicol. Ind. Health, 2017, 33(3), 265-276.
[http://dx.doi.org/10.1177/0748233716637543] [PMID: 27102426]
[12]
Dorostghoal, M.; Seyyednejad, S.M.; Jabari, A. Protective effects of Fumaria parviflora L. on lead-induced testicular toxicity in male rats. Andrologia, 2014, 46(4), 437-446.
[http://dx.doi.org/10.1111/and.12100] [PMID: 23611729]
[13]
Silbergeld, E.K.; Waalkes, M.; Rice, J.M. Lead as a carcinogen: experimental evidence and mechanisms of action. Am. J. Ind. Med., 2000, 38(3), 316-323.
[http://dx.doi.org/10.1002/1097-0274(200009)38:3<316::AID-AJIM11>3.0.CO;2-P] [PMID: 10940970]
[14]
Metryka, E.; Chibowska, K.; Gutowska, I.; Falkowska, A.; Kupnicka, P.; Barczak, K.; Chlubek, D.; Baranowska-Bosiacka, I. Lead (Pb) exposure enhances expression of factors associated with inflammation. Int. J. Mol. Sci., 2018, 19(6), 1813.
[http://dx.doi.org/10.3390/ijms19061813] [PMID: 29925772]
[15]
Alhusaini, A.; Fadda, L.; Hasan, I.H.; Zakaria, E.; Alenazi, A.M.; Mahmoud, A.M. Curcumin ameliorates lead-induced hepatotoxicity by suppressing oxidative stress and inflammation, and modulating Akt/GSK-3β signaling pathway. Biomolecules, 2019, 9(11), 703.
[http://dx.doi.org/10.3390/biom9110703] [PMID: 31694300]
[16]
Aladaileh, S.H.; Saghir, S.A.M.; Murugesu, K.; Sadikun, A.; Ahmad, A.; Kaur, G.; Mahmoud, A.M.; Murugaiyah, V. Antihyperlipidemic and antioxidant effects of Averrhoa Carambola extract in high-fat diet-fed rats. Biomedicines, 2019, 7(3), 72.
[http://dx.doi.org/10.3390/biomedicines7030072] [PMID: 31527433]
[17]
Abukhalil, M.H.; Hussein, O.E.; Bin-Jumah, M.; Saghir, S.A.M.; Germoush, M.O.; Elgebaly, H.A.; Mosa, N.M.; Hamad, I.; Qarmush, M.M.; Hassanein, E.M.H.; Kamel, E.M.; Hernandez-Bautista, R.; Mahmoud, A.M. Farnesol attenuates oxidative stress and liver injury and modulates fatty acid synthase and acetyl-CoA carboxylase in high cholesterol-fed rats. Environ. Sci. Pollut. Res. Int., 2020, 27(24), 30118-30132.
[http://dx.doi.org/10.1007/s11356-020-09296-w] [PMID: 32449150]
[18]
Elsayed, R. H.; Kamel, E. M.; Mahmoud, A. M.; El-Bassuony, A. A.; Bin-Jumah, M.; Lamsabhi, A. M.; Ahmed, S. A. Rumex dentatus L. phenolics ameliorate hyperglycemia by modulating hepatic key enzymes of carbohydrate metabolism, oxidative stress and PPARγ in diabetic rats Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2020, 138, 111202.
[19]
Alhusaini, A.; Fadda, L.; Hasan, I.H.; Ali, H.M.; El Orabi, N.F.; Badr, A.M.; Zakaria, E.; Alenazi, A.M.; Mahmoud, A.M. Arctium lappa root extract prevents lead-induced liver injury by attenuating oxidative stress and inflammation, and activating Akt/GSK-3β signaling. Antioxidants (Basel, Switzerland), 2019, 8(12)
[20]
Abubakar, K.; Muhammad Mailafiya, M.; Danmaigoro, A.; Musa Chiroma, S.; Abdul Rahim, E.B.; Abu Bakar Zakaria, M.Z. Curcumin attenuates lead-induced cerebellar toxicity in rats via chelating activity and inhibition of oxidative stress. Biomolecules, 2019, 9(9), E453.
[http://dx.doi.org/10.3390/biom9090453] [PMID: 31489882]
[21]
Elsheikh, N. A. H.; Omer, N. A.; Yi-Ru, W.; Mei-Qian, K.; Ilyas, A.; Abdurahim, Y.; Wang, G.-L. Protective effect of betaine against lead-induced testicular toxicity in male mice Andrologia, 2020.
[22]
Hassanein, E.H.M.; Sayed, A.M.; Hussein, O.E.; Mahmoud, A.M. Coumarins as modulators of the Keap1/Nrf2/ARE signaling pathway. Oxid. Med. Cell. Longev., 2020, 2020, 1675957.
[http://dx.doi.org/10.1155/2020/1675957] [PMID: 32377290]
[23]
Khalil, H.S.; Sedky, N.K.; Amin, K.M.; Abd Elhafez, O.M.; Arafa, R.K. Visnagin and benzofuran scaffold-based molecules as selective cyclooxygenase-2 inhibitors with anti-inflammatory and analgesic properties: design, synthesis and molecular docking. Future Med. Chem., 2019, 11(7), 659-676.
[http://dx.doi.org/10.4155/fmc-2018-0398] [PMID: 30958028]
[24]
Pasari, L. P.; Khurana, A.; Anchi, P.; Aslam Saifi, M.; Annaldas, S.; Godugu, C. Visnagin attenuates acute pancreatitis via Nrf2/NFkappaB pathway and abrogates associated multiple organ dysfunction. Biomed. Pharmacother., 2019, 112, 108629.
[25]
Asnani, A.; Zheng, B.; Liu, Y.; Wang, Y.; Chen, H.H.; Vohra, A.; Chi, A.; Cornella-Taracido, I.; Wang, H.; Johns, D.G.; Sosnovik, D.E.; Peterson, R.T. Highly potent visnagin derivatives inhibit Cyp1 and prevent doxorubicin cardiotoxicity. JCI Insight, 2018, 3(1), e96753.
[http://dx.doi.org/10.1172/jci.insight.96753] [PMID: 29321375]
[26]
Lee, J.K.; Jung, J.S.; Park, S.H.; Park, S.H.; Sim, Y.B.; Kim, S.M.; Ha, T.S.; Suh, H.W. Anti-inflammatory effect of visnagin in lipopolysaccharide-stimulated BV-2 microglial cells. Arch. Pharm. Res., 2010, 33(11), 1843-1850.
[http://dx.doi.org/10.1007/s12272-010-1117-1] [PMID: 21116788]
[27]
Vanachayangkul, P.; Byer, K.; Khan, S.; Butterweck, V. An aqueous extract of Ammi visnaga fruits and its constituents khellin and visnagin prevent cell damage caused by oxalate in renal epithelial cells. Phytomedicine, 2010, 17(8-9), 653-658.
[http://dx.doi.org/10.1016/j.phymed.2009.10.011] [PMID: 20036111]
[28]
Batra, N.; Nehru, B.; Bansal, M.P. The effect of zinc supplementation on the effects of lead on the rat testis. Reprod. Toxicol., 1998, 12(5), 535-540.
[http://dx.doi.org/10.1016/S0890-6238(98)00030-6] [PMID: 9763245]
[29]
Björndahl, L.; Söderlund, I.; Kvist, U. Evaluation of the one-step eosin-nigrosin staining technique for human sperm vitality assessment. Hum. Reprod., 2003, 18(4), 813-816.
[http://dx.doi.org/10.1093/humrep/deg199] [PMID: 12660276]
[30]
Nna, V.U.; Osim, E.E. Testicular toxicity following separate and combined administration of PDE5 inhibitors and opioid: assessment of recovery following their withdrawal. Andrologia, 2017, 49(6)
[http://dx.doi.org/10.1111/and.12669] [PMID: 27484363]
[31]
Ohkawa, H.; Ohishi, N.; Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem., 1979, 95(2), 351-358.
[http://dx.doi.org/10.1016/0003-2697(79)90738-3] [PMID: 36810]
[32]
Beutler, E.; Duron, O.; Kelly, B.M. Improved method for the determination of blood glutathione. J. Lab. Clin. Med., 1963, 61, 882-888.
[PMID: 13967893]
[33]
Marklund, S.; Marklund, G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur. J. Biochem., 1974, 47(3), 469-474.
[http://dx.doi.org/10.1111/j.1432-1033.1974.tb03714.x] [PMID: 4215654]
[34]
Cohen, G.; Dembiec, D.; Marcus, J. Measurement of catalase activity in tissue extracts. Anal. Biochem., 1970, 34, 30-38.
[http://dx.doi.org/10.1016/0003-2697(70)90083-7] [PMID: 5440916]
[35]
Hickey, E.J.; Raje, R.R.; Reid, V.E.; Gross, S.M.; Ray, S.D. Diclofenac induced in vivo nephrotoxicity may involve oxidative stress-mediated massive genomic DNA fragmentation and apoptotic cell death. Free Radic. Biol. Med., 2001, 31(2), 139-152.
[http://dx.doi.org/10.1016/S0891-5849(01)00560-3] [PMID: 11440826]
[36]
Kim, C.Y.; Chung, K.S.; Cheon, S.Y.; Lee, K.; Ham, I.; Choi, H.Y.; Cho, Y.B.; Cho, B.H.; Mok, S.Y.; An, H.J. Hypolipidemic effects of HVC1 in a high cholesterol diet‑induced rat model of hyperlipidemia. Mol. Med. Rep., 2016, 14(4), 3152-3158.
[http://dx.doi.org/10.3892/mmr.2016.5615] [PMID: 27510839]
[37]
Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 2001, 25(4), 402-408.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[38]
Biswas, N.M.; Ghosh, P. Effect of lead on male gonadal activity in albino rats. Kathmandu Univ Med J (KUMJ), 2004, 2(1), 43-46.
[PMID: 19780287]
[39]
Mabrouk, A.; Ben Cheikh, H. Thymoquinone supplementation ameliorates lead-induced testis function impairment in adult rats. Toxicol. Ind. Health, 2016, 32(6), 1114-1121.
[http://dx.doi.org/10.1177/0748233714548474] [PMID: 25216800]
[40]
Oduwole, O.O.; Peltoketo, H.; Huhtaniemi, I.T. Role of Follicle-Stimulating Hormone in Spermatogenesis. Front. Endocrinol. (Lausanne), 2018, 9(763), 763.
[http://dx.doi.org/10.3389/fendo.2018.00763] [PMID: 30619093]
[41]
Bremer, A.A.; Miller, W.L. Regulation of Steroidogenesis.Cellular Endocrinology in Health and Disease; Ulloa-Aguirre, A.; Conn, P.M., Eds.; Academic Press: Boston, 2014, pp. 207-227.
[http://dx.doi.org/10.1016/B978-0-12-408134-5.00013-5]
[42]
Hassan, E.; Kahilo, K.; Kamal, T.; Hassan, M.; Saleh Elgawish, M. The protective effect of epigallocatechin-3-gallate on testicular oxidative stress in lead-induced toxicity mediated by Cyp19 gene / estradiol level. Toxicology, 2019, 422, 76-83.
[http://dx.doi.org/10.1016/j.tox.2019.04.015] [PMID: 31054310]
[43]
El-Magd, M.A.; Kahilo, K.A.; Nasr, N.E.; Kamal, T.; Shukry, M.; Saleh, A.A. A potential mechanism associated with lead-induced testicular toxicity in rats. Andrologia, 2017, 49(9), e12750.
[http://dx.doi.org/10.1111/and.12750] [PMID: 28000947]
[44]
Smathers, R.L.; Galligan, J.J.; Stewart, B.J.; Petersen, D.R. Overview of lipid peroxidation products and hepatic protein modification in alcoholic liver disease. Chem. Biol. Interact., 2011, 192(1-2), 107-112.
[http://dx.doi.org/10.1016/j.cbi.2011.02.021] [PMID: 21354120]
[45]
Linseman, D.A.; Butts, B.D.; Precht, T.A.; Phelps, R.A.; Le, S.S.; Laessig, T.A.; Bouchard, R.J.; Florez-McClure, M.L.; Heidenreich, K.A. Glycogen synthase kinase-3beta phosphorylates Bax and promotes its mitochondrial localization during neuronal apoptosis. J. Neurosci., 2004, 24(44), 9993-10002.
[http://dx.doi.org/10.1523/JNEUROSCI.2057-04.2004] [PMID: 15525785]

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