Dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.

Salinomycin is used as an antibiotic in animal husbandry. Its implication in cancer therapy has recently been proposed. Present study evaluated the toxic effects of Salinomycin on male reproductive system of mice. Doses of 1, 3 or 5 mg/kg of Salinomycin were administered daily for 28 days. Half of t...

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Autores principales:	Olajumoke Omolara Ojo, Smrati Bhadauria, Srikanta Kumar Rath
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1bce5710c39f427baf381b506291810c
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spelling	oai:doaj.org-article:1bce5710c39f427baf381b506291810c2021-11-18T07:39:13ZDose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.1932-620310.1371/journal.pone.0069086https://doaj.org/article/1bce5710c39f427baf381b506291810c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23840907/?tool=EBIhttps://doaj.org/toc/1932-6203Salinomycin is used as an antibiotic in animal husbandry. Its implication in cancer therapy has recently been proposed. Present study evaluated the toxic effects of Salinomycin on male reproductive system of mice. Doses of 1, 3 or 5 mg/kg of Salinomycin were administered daily for 28 days. Half of the mice were sacrificed after 24 h of the last treatment and other half were sacrificed 28 days after withdrawal of treatment. Effects of SAL on body and reproductive organ weights were studied. Histoarchitecture of testis and epididymis was evaluated along with ultrastructural changes in Leydig cells. Serum and testicular testosterone and luteinizing hormones were estimated. Superoxide dismutase, reduced glutathione, lipid peroxidation, catalase and lactate dehydrogenase activities were measured. Spermatozoa count, morphology, motility and fertility were evaluated. Expression patterns of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage proteins (CYP11A1) were assessed by Western blotting. Salinomycin treatment was lethal to few mice and retarded body growth in others with decreased weight of testes and seminal vesicles in a dose dependent manner. Seminiferous tubules in testes were disrupted and the epithelium of epididymis showed frequent occurrence of vacuolization and necrosis. Leydig cells showed hypertrophied cytoplasm with shrunken nuclei, condensed mitochondria, proliferated endoplasmic reticulum and increased number of lipid droplets. Salinomycin decreased motility and spermatozoa count with increased number of abnormal spermatozoa leading to infertility. The testosterone and luteinizing hormone levels were decreased in testis but increased in serum at higher doses. Depletion of superoxide dismutase and reduced glutathione with increased lipid peroxidation in both testis and epididymis indicated generation of oxidative stress. Suppressed expression of StAR and CYP11A1 proteins indicates inhibition of steroidogenesis. Spermatogenesis was however observed in testis 28 days after Salinomycin withdrawal. The results indicate reversible dose-dependent adverse effects of Salinomycin on male reproductive system of mice.Olajumoke Omolara OjoSmrati BhadauriaSrikanta Kumar RathPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e69086 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Olajumoke Omolara Ojo Smrati Bhadauria Srikanta Kumar Rath Dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.
description	Salinomycin is used as an antibiotic in animal husbandry. Its implication in cancer therapy has recently been proposed. Present study evaluated the toxic effects of Salinomycin on male reproductive system of mice. Doses of 1, 3 or 5 mg/kg of Salinomycin were administered daily for 28 days. Half of the mice were sacrificed after 24 h of the last treatment and other half were sacrificed 28 days after withdrawal of treatment. Effects of SAL on body and reproductive organ weights were studied. Histoarchitecture of testis and epididymis was evaluated along with ultrastructural changes in Leydig cells. Serum and testicular testosterone and luteinizing hormones were estimated. Superoxide dismutase, reduced glutathione, lipid peroxidation, catalase and lactate dehydrogenase activities were measured. Spermatozoa count, morphology, motility and fertility were evaluated. Expression patterns of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage proteins (CYP11A1) were assessed by Western blotting. Salinomycin treatment was lethal to few mice and retarded body growth in others with decreased weight of testes and seminal vesicles in a dose dependent manner. Seminiferous tubules in testes were disrupted and the epithelium of epididymis showed frequent occurrence of vacuolization and necrosis. Leydig cells showed hypertrophied cytoplasm with shrunken nuclei, condensed mitochondria, proliferated endoplasmic reticulum and increased number of lipid droplets. Salinomycin decreased motility and spermatozoa count with increased number of abnormal spermatozoa leading to infertility. The testosterone and luteinizing hormone levels were decreased in testis but increased in serum at higher doses. Depletion of superoxide dismutase and reduced glutathione with increased lipid peroxidation in both testis and epididymis indicated generation of oxidative stress. Suppressed expression of StAR and CYP11A1 proteins indicates inhibition of steroidogenesis. Spermatogenesis was however observed in testis 28 days after Salinomycin withdrawal. The results indicate reversible dose-dependent adverse effects of Salinomycin on male reproductive system of mice.
format	article
author	Olajumoke Omolara Ojo Smrati Bhadauria Srikanta Kumar Rath
author_facet	Olajumoke Omolara Ojo Smrati Bhadauria Srikanta Kumar Rath
author_sort	Olajumoke Omolara Ojo
title	Dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.
title_short	Dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.
title_full	Dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.
title_fullStr	Dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.
title_full_unstemmed	Dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.
title_sort	dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/1bce5710c39f427baf381b506291810c
work_keys_str_mv	AT olajumokeomolaraojo dosedependentadverseeffectsofsalinomycinonmalereproductiveorgansandfertilityinmice AT smratibhadauria dosedependentadverseeffectsofsalinomycinonmalereproductiveorgansandfertilityinmice AT srikantakumarrath dosedependentadverseeffectsofsalinomycinonmalereproductiveorgansandfertilityinmice
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Dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.

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