Toxic effects of different doses of cyclophosphamide on the reproductive parameters of male mice

Abstract

The cyclophosphamide is used in cancer treatment. The aim of this study was evaluating the effect of different doses of this drug on male mice reproductive parameters. The cyclophosphamide was administered in the doses 100, 150, 200 e 250 mg.kg -1 , intraperitoneal route, for six weeks. As a result, it was observed a decrease in body mass and a decrease in testicles and kidney's weight, in all animals treated with cyclophosphamide. Only the groups that received the doses 100, 150 mg.kg -1 of cyclophosphamide were able to fertilize their females. There was higher incidence of post-implantation losses, reabsorptions and decrease in fetal viability in the group that received the dose of 150 mg.kg . Based on the methodology used and results obtained, it was concluded that the cyclophosphamide was toxic, considering the decrease in animal's body mass and testicle's weight; promoted hepatotoxicity and nephrotoxic effect; influenced in the animals spermatogenesis taking them to infertility and/or subfertility; decreased fetal viability, despite it didn't cause significant malformations in the offspring.Uniterms: Cyclophosphamide/effects. Cyclophosphamide/toxicity. Spermatogenesis/experimental study. Chemotherapeutics/adverse effects. Fertility/experimental study.A ciclofosfamida é utilizada no tratamento de câncer. Este estudo visa avaliar os efeitos das diferentes doses do fármaco nos parâmetros reprodutivos de camundongos machos. A ciclofosfamida foi administrada nas doses de 100, 150, 200 e 250 mg kg -1 , via intraperitoneal por seis semanas. Como resultado observou-se diminuição de massa corporal, redução no peso de testículos e rins em todos os animais tratados com a ciclofosfamida. Apenas os grupos que receberam as doses de 100 e 150 mg kg -1 do quimioterápico foram capazes de fertilizar as fêmeas. Houve maior incidência de perdas pós-implantação, reabsorção e diminuição da viabilidade fetal no grupo que recebeu a dose de 150 mg kg -1 . Observou-se redução nos pesos dos epidídimos e fígado dos animais tratados com as doses de 150, 200 e 250 mg kg -1 . Espermatozóides anômalos foram encontrados nas doses de 200 e 250mg kg -1 . Com base na metodologia empregada e nos resultados obtidos, conclui-se que a ciclofosfamida foi tóxica considerando-se a redução de massa corporal e o peso dos testículos dos animais; promoveu hepatotoxicidade e efeito nefrotóxico; influenciou na espermatogênese dos animais de forma a levá-los a um estado de infertilidade e/ou subfertilidade; diminuiu viabilidade fetal, entretanto não causou malformações significativas na prole.Unitermos: Ciclofosfamida/efeitos. Ciclofosfamida/toxicidade. Espermatogênese/estudo experimental. Quimioterápicos/efeitos adversos. Fertilidade/ estudo experimental.

Cyclophosphamide-induced male subfertility in mice: An assessment of the potential benefits of Maca supplement

“…Figures 3c and 4c), there was minimal swelling and cellular debris; and the duct epithelium and cells were better preserved, compared to the cyclophosphamide-only group. There was also loss of interstitial space between In this study, administration of cyclophosphamide was associated with significant weight loss, which is consistent with reports of previous studies in rodents (Kanno, Sensiate, Aparecida de Paula, & Salles, 2009;Kumar, Singh, & Reddy, 2013;Latha & Panikkar, 1999;Myers et al, 2017). In the group where Maca alone was administered at 500 mg/kg (Figures 3e and 4e), there was an increase in sperm concentration within the ducts; duct epithelium and cells were normal and well preserved.…”

The effect of melatonin on the testes of rats treated with cyclophosphamide

“…These results have been confirmed by previous studies [1,14], in which a significant reduction in the weight of the testes following CP treatment has been reported. These results have been confirmed by previous studies [1,14], in which a significant reduction in the weight of the testes following CP treatment has been reported.…”

“…Several studies on male rats have confirmed that the administration of CP resulted in oligospermia, azoospermia, and histological alterations in the testes [1,13,14]. A wide range of adverse effects including reproductive toxicity have been found following CP treatment in humans and experimental animals.…”

“…Cyclophosphamide (CP) is used in the treatment of certain malignant tumors such as lymphomas, leukemias, and in some non-neoplastic autoimmune diseases such as lupus erythematosus and glomerulonephritis [1]. Cyclophosphamide (CP) is used in the treatment of certain malignant tumors such as lymphomas, leukemias, and in some non-neoplastic autoimmune diseases such as lupus erythematosus and glomerulonephritis [1].…”

Evolução do estado nutricional de mulheres com cânceres de mama, ovário ou útero e associação com a ingestão alimentar e sintomas gastrintestinais

“…Este é um substrato da enzima aldeído desidrogenase e, em células que contém esta enzima, a maior parte do 4-HOCy é oxidado a carboxifosfamida (um agente citotóxico) e excretado na urina. Consequentemente, células contendo elevada concentração de aldeído desidrogenase são resistentes aos metabólitos da ciclofosfamida (DeVITA; HELLMAN;ROSENBERG, 2000;JENSEN et al, 2008;KANNO et al, 2009) .…”