Bisphenol A induces testicular oxidative stress in mice leading to ferroptosis / 亚洲男科学杂志(英文版)

Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.

Efficacy of Essential Trace Elements Supplementation on Mineral Composition, Sperm Characteristics, Antioxidant Status, and Genotoxicity in Testis of Tebuconazole-treated Rats / 生物医学与环境科学（英文）

Objective@#This research was performed to evaluate the effect of tebuconazole (TBZ) on reproductive organs of male rats and to assess the protective role of combined essential trace elements in alleviating the detrimental effect of TBZ on male reproductive function.@*Methods@#For this purpose, 48 rats were exposed to 100 mg/kg TBZ, TBZ supplemented with zinc (Zn), selenium (Se), copper (Cu), and iron (Fe), TBZ + (Se + Zn); TBZ + Cu; or TBZ + Fe. The experiment was conducted for 30 consecutive days.@*Results@#TBZ caused a significant perturbation in mineral levels and reduction in reproductive organs weights, plasma testosterone level, and testicular antioxidant enzyme activities. The TBZ-treated group also showed a significant increase in sperm abnormalities (count, motility, and viability percent), plasma follicle-stimulating hormone and luteinizing hormone concentrations, lipid peroxidation, protein oxidation, and severe DNA degradation in comparison with the controls. Histopathologically, TBZ caused testis impairments. Conversely, treatment with trace elements, in combination or alone, improved the reproductive organ weights, sperm characteristics, TBZ-induced toxicity, and histopathological modifications in testis.@*Conclusion@#TBZ exerts significant harmful effects on male reproductive system. The concurrent administration of trace elements reduces testis dysfunction, fertility, and toxicity induced by TBZ.

Screening and bioinformatics analysis of specific microRNAs in testes of rats exposed to cigarette smoke

Objective: To identify effects of cigarette smoke on the male reproductive capacity and to explore the miRNA expression in the testes after cigarette smoke exposure. Methods: Eighty male rats were conducted by factorial analysis of variance designed for cigarette exposure. A microarray was employed to detect the differential expression of miRNA in the testis tissue of smoke-exposed rats. Results: Four miRNAs (miR-138-5p, miR-181d-5p, miR-19a-3p, and miR-3588) were significantly downregulated and one miRNA (miR-155-5p) was upregulated in the testes of smoke-exposed rats compared with control rats. This result was further confirmed by a quantitative RT-PCR assay, and pathological changes were observed in the testes. Bioinformatics analysis showed that the predicted target genes were closely related to the regulation of the apoptosis pathway. Conclusions: miRNA may play an important role in the smoke-exposure-induced testicular toxicity of male rats.

Protective Roles of Melatonin against Acrylamide-induced Testicular Toxicity in Rats / 中山大学学报(医学科学版)

[Objective] The present study aimed to determine the protective role of Melatonin (MT) against Acrylamide (AA)-induced testicular toxicity and the potential molecular mechanism.[Methods] The animals were randomly divided into three groups,the control group (n =12),the AA group (n =12) and the AA+MT group (n =12).The rats in the AA and AA + MT group were gavaged with AA at a dose of 15 mg/(kg · day) for 4 consecutive weeks.After 3 weeks of AA treatment,MT was intraperitoneally injected 30 minutes before AA treatment at 10 mg/(kg· day) for 1 week in the AA + MT rats.Subsequently,the mitochondrial membrane potential measurement,TUNEL assay,Western blot and electron microscopic techniques were applied in the present study.[Results] The results showed that AA could decrease the testis mitochondrial membrane potential (P ＜ 0.05) which could be recovered by MT (P ＜ 0.05).Moreover,MT induced down-regulation of Bax expression and up-regulation of Bcl-2 expression in the testis,compared with AA rats.The amelioration of testicular apoptosis was further confirmed by the TUNEL labeling.Western blot results suggested that the decreased ratios of Bcl-2/Bax and Bcl-xL/Bak in the AA group (both P ＜ 0.05) could be recovered by MT treatment (both P ＜ 0.05).The levels of Cyt-c,Casp-3,p53 and NF-κB in AA group were markedly elevated compared with the control (all P ＜ 0.05),and reduced in MT treatment group (all P ＜ 0.05).MT could relieve abnormal mitochondrial structures in the seminiferous tubule in the electron microscopic level.[Conclusion] MT may exert productive effect through its anti-apoptotic properties associated with mitochondria.

Antioxidant capacity and acute testicular toxicity of Leucaena leucocephala aqueous shoot tips plus young leaves extracts / Capacidad antioxidante y toxicidad testicular aguda de brotes acuosos con extracto de hojas nuevas de Leucaena leucocephala

This study aimed to determine the antioxidant capacity of the Leucaena leucocephala aqueous shoot tips plus young leaves (LL-spl) extracts among three different fractions (LL-spl 10, 20, and 40 min) and to examine its acute toxicity on male reproductive parameters. The amount of the total phenolics in LL-spl extract was determined using a Folin-Ciocalteu reagent method and its antioxidant capacity was analyzed using 1, 1-diphenyl l-2-picrylhydrazyl radical scavenging and ferric reducing antioxidant powder methods. The LL-spl extract fraction with highest antioxidant capacity was used in animal treating. Male rats were divided into three groups (n= 5); control and groups treated with LL-spl 400 and 600 mg/Kg body weight for consecutive 40 days. The results showed that the LL-spl 40 min fraction possessed the highest antioxidant capacity. In addition, the LL-spl 400 and 600 groups showed no differences in weights of body, testis and epididymis, serum testosterone levels, and expression of testicular steroidogenic acute regulatory (StAR) protein. Significantly, LL-spl extract reduced the weight of seminal vesicle, sperm concentration, and seminiferous diameters compared with control. Moreover, LL-spl extract had adverse effect on testicular histology in inducing of seminiferous atrophy and degeneration including dilated blood vessels in interstitial tissue. It was concluded that although LL-spl extract possessing antioxidant capacity, in short term consumptions, it could be toxic to some male reproductive organs especially damaging testicular tissues.

El objetivo fue determinar la capacidad antioxidante del extracto de brotes acuosos con hojas nuevas de Leucaena leucocephala (LL-spl) en tres fracciones diferentes (LL-SPL 10, 20 y 40 min), además de examinar su toxicidad aguda sobre los parámetros reproductivos masculinos. Se determinó la cantidad de los fenoles totales en el extracto de LL-spl utilizando un método reactivo de Folin-Ciocalteu. La capacidad antioxidante se analizó por medio de 1-difenil-2-picrilhidracilo y/o métodos de reducción férrica de la capacidad antioxidante. La fracción de extracto LL-spl con mayor capacidad antioxidante fue utilizada en el tratamiento de los animales. Ratas macho fueron divididas en tres grupos (n= 5): el control y los grupos tratados con LL-spl 400 y 600 mg/kg peso corporal por 40 días consecutivos. El resultado mostró que la fracción LL-spl 40 min poseía la mayor capacidad antioxidante. Además, los grupos 400 y 600 LL-spl no mostraron diferencias según el peso corporal, testículos y epidídimo, niveles de testosterona y la expresión de proteínas testiculares. El extracto de LL-spl redujo de manera significativa el peso de la vesícula seminal, la concentración de espermatozoides y los diámetros de los túbulos seminíferos en comparación con el control. Por otra parte, el extracto de LL-spl tuvo un efecto adverso sobre la histología testicular por la inducción de atrofia y degeneración de los túbulos seminíferos, incluyendo a vasos sanguíneos dilatados en el tejido intersticial. Si bien el extracto LL-spl posee una capacidad antioxidante, ésta podría ser tóxica en el consumo a corto plazo para algunos órganos reproductores masculinos y especialmente dañino para los tejidos testiculares.

Comparison of antioxidant effects of kolaviron and vitamin C interventions on testicular structures following nevirapine administration in Sprague-Dawley rats / Comparación de los efectos antioxidantes en la intervención con kolaviron y vitamina C sobre las estructuras testiculares después de la administración de nevirapina en ratas Sprague-Dawley

Testicular toxicity has been implicated in highly active anti-retroviral therapy (HAART) treatment. Hence there is need to identify an effective antioxidant product that can alleviate testicular necrosis due to HAART administration. Forty eight adult male Sprague-Dawley rats were used in this study. The animals were divided into eight (8) groups: A-H (n= 6). Group A animals received normal saline as the control; Group B was given Nevirapine (Nv); Group C was given Kolaviron (Kv); Group D was given vitamin C; Group E was given Nv and Kv; Group F was given Nv and Vitamin C; Group G was given Nv for 56 d and Kv for 28 d serving as a withdrawal group; Group H was given corn oil. Nv, Kv and Vit. C were given at 1.54, 200 and 250 (mg·kg)/bw respectively while all administrations were through oral gavage. The body weights were taken every other day. Thereafter, they were anaesthetized with halothane. The testes were excised, weighed, fixed in Bouin's fluid and stained with H&E while the epididymes removed for semen fluid analyses. The results showed a significant (P<0.05) decrease in sperm motility in group E (Nevirapine + kolaviron) when compared with group F (Nevirapine + Vitamin C) while Sperm count was not significantly different (P>0.05) across the groups. The testicular histoarchitectural studies revealed indistinct spermatogonia, necrotic interstititial endocrine cells in the altered interstitial space, fragmented spermatids, atrophy of mature spermatocytes, degenerated germ cells, obliterated seminiferous tubules lumen, undifferentiated spermatogonia and cellular debris in the somniferous tubules lumen of nevirapine administered group but normal across the other groups. In the testis, there were no significant reduction in SOD, Catalase and GPx activities but a significant decrease in GST activity (P<0.001) when group E was compared with group F. In conclusion, vitamin C presents a better remediation in nevirapine induced spermiotoxicity compared to kolaviron in Sprague-Dawley rats.

La toxicidad testicular ha sido implicada en la terapia antirretroviral altamente activa (TARAA). Por lo tanto existe la necesidad de identificar un producto antioxidante eficaz que pueda aliviar la necrosis testicular en la administración de la TARAA. Cuarenta y ocho ratas macho Sprague-Dawley adultas fueron utilizadas. Los animales se dividieron en ocho (8) grupos: AH (n= 6). Grupo A, animales recibieron solución salina normal como el control; Grupo B, recibió Nevirapina (Nv); Grupo C, recibió Kolaviron (Kv); Grupo D, recibió vitamina C; Grupo E, recibió Nv y Kv; Grupo F, recibió Nv y vitamina C; Grupo G, recibió Nv durante 56 d y Kv por 28 d como un grupo de retirada; Grupo H, recibió aceite de maíz. Nv, Kv y Vit. C se administraron en dosis de 1, 54, 200 y 250 (mg · kg) de peso corporal respectivamente; todas las administraciones fueron por sonda oral. Los pesos corporales se tomaron cada dos días. A partir de ese momento los animales fueron anestesiados con halotano. Los testículos fueron extirpados, pesados y fijados en solución de Bouin y teñidos con H&E, mientras que el epidídimo se retiró para analizar el semen. Los resultados mostraron un descenso (p<0,05) en la motilidad de los espermatozoides en el grupo E (Nevirapina + Kolaviron) en comparación con el grupo F (Nevirapina + vitamina C), mientras que el recuento espermático no mostró diferencias significativas (P>0,05) entre los grupos. El estudio de la histoarquitectura testicular reveló espermatogonias indiferenciadas, con células intersticiales necróticas en el espacio intersticial y espermátidas fragmentadas. Además, en el grupo que recibió Nevirapina mostró espermatocitos maduros atrofiados, degeneración de células germinales, lumen de los túbulos seminíferos obliterados, espermatogonias indiferenciadas y restos celulares en el lumen de los tubulos seminíferos. En el resto de los grupos los resultados fueron normales. En el testículo hubo una reducción significativa en las actividades de la superóxido dismutasa, catalasa y glutatión peroxidasa, pero una disminución significativa en la actividad glutatión S-transferasa (P <0,001) al comparar los grupo E y F.

Ameliorative Effect of Punica Granatum Ethanolic Extract in Cyclophosphamide Induced Testicular Toxicity in Male Wistar Rats.

Aim: To explore the potential role of Punica granatum ethanolic extract (PGEE) in Cyclophosphamide (CP) induced testicular toxicity. Methods: Healthy male Wistar rats were allotted to 4 groups (N=6, each) Group I: Control, Group II: CP 15mg/kg twice a week, Group III: PGEE 100mg/kg, Group IV: CP and PGEE for 28 days. At the end of the treatment period, organ weight, body weight, epididymal sperm count, motility, morphology, SOD, catalase, GSH, ACP & testosterone level in the testis were evaluated. Results: The CP treated rats showed toxicity evidenced by decreased organ and body weight, decreased sperm quality and testosterone level also increase in MDA and decrease in antioxidants SOD, GSH indicating oxidative stress. In contrast PGEE co-treatment with CP resulted in significant restoration of the above mentioned parameters. Conclusion: These results indicate that PGEE attenuates CP induced testicular toxicity through its ROS scavenging activity.

Lead Nitrate Induced Testicular Toxicity in Diabetic and Non-Diabetic Rats: Protective Role of Sodium Selenite

Among heavy met als, lead is one of the common pollutants found in the environment and biological system. In the present study, streptozotocin-induced diabetic and normal non-diabetic male Wistar rats were given sodium selenite (1.0 mg/kg bw), lead nitrate (22.5 mg/kg bw) and sodium selenite plus lead nitrate (1.0 mg/kg+22.5 mg/kg bw, respectively) through gavage. At the end of 4th week, malondialdehyde (MDA) levels, antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST)], and histopathological changes of testes were investigated compared to the control group. No significant differences were observed between the control and sodium selenite treated groups. However, lead nitrate increased the levels of MDA, SOD, CAT, GPx and GST activities compared with the control group in diabetic and non-diabetic rats. Light microscopic analyses revealed that lead nitrate induced numerous histopathological changes in testis tissues of diabetic and non-diabetic rats. In the diabetic and non-diabetic sodium selenite plus lead nitrate treated groups, there were statistically significantly decreased MDA levels and antioxidant enzymes activities and mild pathological changes. As a result, sodium selenite significantly reduced lead nitrate induced testicular toxicity for both diabetic and non-diabetic rats.

The Hepatotoxicity and Testicular Toxicity Induced by Arecoline in Mice and Protective Effects of Vitamins C and E

Arecoline is a major alkaloid of areca nuts which are widely chewed by southeast Asian and it manifests various toxic effects in different organs of human and animals. In this work, mature mice were treated by vitamins C plus E, arecoline, or both daily for four weeks. The results showed that arecoline significantly increased the levels of serum alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and significantly decreased the levels of reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) in the liver tissues. Additionally, the body weight, testis weight, sperm counts, motility and normal sperms also were significantly decreased. The supplement of vitamins C and E can bring the activities of ALP and GPT to normal levels and partially restore the sperm counts compared to the arecoline-treated group but have no other positive effects. In conclusion, the vitamins C and E partially attenuated the arecoline-induced hepatotoxiciy but basically had on protective effects against the arecoline-induced testicular toxicity.

Protective effect of diallyl disulfide on cyclophosphamide-induced testicular toxicity in rats / 한국실험동물학회지

This study investigated the protective effects of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced testicular toxicity in male rats. DADS was gavaged to rats once daily for 3 days at 100 mg/kg/day. One hour after the final DADS treatment, the rats were given a single intraperitoneal dose of 150 mg/kg CP. All rats were killed and necropsied on day 56 after CP treatment. Parameters of testicular toxicity included reproductive organ weight, testicular sperm head count, epididymal sperm motility and morphology, epididymal index, and histopathologic examinations. The CP treatment caused a decrease in body weight, testicular sperm head count, epididymal sperm motility, and epididymal index. The histopathological examination revealed various morphological alterations, characterized by degeneration of spermatogonia/spermatocytes, vacuolization, and decreased number of spermatids/spermatocytes in the testis, and cell debris and mild oligospermia in the ductus epididymis. In contrast, DADS pretreatment effectively attenuated the testicular toxicity caused by CP, including decreased sperm head count, epididymal sperm motility, and epididymal index and increased histopathological alterations in the testis and epididymis. These results indicate that DADS attenuates testicular toxicity induced by CP in rats.

Testicular toxicity evaluation of two antimony compounds, antimony trioxide and antimony potassium tartrate, in rats and mice

<p><b>OBJECTIVES</b>Testicular toxicities of antimony compounds were evaluated in rats and mice. The slightly water-soluble antimony compound antimony trioxide (ATO) and the highly water-soluble antimony compound antimony potassium tartrate (APT) were examined.</p><p><b>METHODS</b>Daily doses of the compounds were 27.4, 12.0 and 1,200 mg/kg body weight in the APT group, low-ATO group and high-ATO group, respectively. The corresponding daily doses of antimony were 10, 10 and 1,000 mg/kg body weight, in the APT group, low-ATO group and high-ATO group, respectively. Both compounds were administered by gavage: rats, 3 days per week for 4 weeks; mice, 5 days per week for 4 weeks.</p><p><b>RESULTS</b>Neither compound reduced the weights of reproductive organs or accessory sex organs nor affected sperm parameters. Few marked histopathologic changes were found in the testes of the treated animals. Even at 1,200 mg/kg body weight, which is greater than the LD(50) of APT, ATO produced no effects.</p><p><b>CONCLUSIONS</b>In this study, it was found that ATO and APT are not toxic to testes in rodents.</p>

Age-dependent Effect of Metabolism and Testicular Toxicity to di(2-ethylhexyl) Phthalate / 대한산업의학회지

OBJECTIVES: The purpose of this study was to evaluate the age-dependent response of testicular toxicity and the mechanism of di(2-ethylhexyl) phthalate (DEHP) induced testicular toxicity. METHODS: DEHP was administered orally in doses of 0, 1.0 and 2.0 g/kg/day, for 7 days, to 3, 6 and 9 week-old Sprague-Dawley rats. Testicular weight and sperm head counts, plasma level of DEHP, mono(2-ethylhexyl) phthalate (MEHP) and testicular lipid peroxidation were measured. Histopathological changes in the testis were observed. RESULTS: Reductions in weight gains, and relative testis weights, were observed in the 3 week-old rats in a dose-dependent manner, but not in the 6 and 9 week-old rats, compared to those of the control rats. Sperm head counts were decreased in the 6 week-old rats exposed to 2.0 g/kg/day, but not in the 9 week-old rats. Testicular atrophy and significant size reduction of the seminiferous tubule were observed in a dose-dependent manner in the 3 week-old rats. The plasma concentrations of MEHP were higher than those of DEHP, with these levels being most elevated in the younger rats. Lipid peroxidation, following exposed to DEHP, was increased in a dose-dependent manner in the 3 week-old, but with no changes in the 6 and 9 week-old rats. CONCLUSIONS: Our results suggest the age related difference observed in the testicular response to the oral administration of DEHP may be due to the metabolism, and that oxidative stress may be related to the mechanism of DEHP induced testicular toxicity.

Age-dependent Effect of Metabolism and Testicular Toxicity to di(2-ethylhexyl) Phthalate / 대한산업의학회지

OBJECTIVES: The purpose of this study was to evaluate the age-dependent response of testicular toxicity and the mechanism of di(2-ethylhexyl) phthalate (DEHP) induced testicular toxicity. METHODS: DEHP was administered orally in doses of 0, 1.0 and 2.0 g/kg/day, for 7 days, to 3, 6 and 9 week-old Sprague-Dawley rats. Testicular weight and sperm head counts, plasma level of DEHP, mono(2-ethylhexyl) phthalate (MEHP) and testicular lipid peroxidation were measured. Histopathological changes in the testis were observed. RESULTS: Reductions in weight gains, and relative testis weights, were observed in the 3 week-old rats in a dose-dependent manner, but not in the 6 and 9 week-old rats, compared to those of the control rats. Sperm head counts were decreased in the 6 week-old rats exposed to 2.0 g/kg/day, but not in the 9 week-old rats. Testicular atrophy and significant size reduction of the seminiferous tubule were observed in a dose-dependent manner in the 3 week-old rats. The plasma concentrations of MEHP were higher than those of DEHP, with these levels being most elevated in the younger rats. Lipid peroxidation, following exposed to DEHP, was increased in a dose-dependent manner in the 3 week-old, but with no changes in the 6 and 9 week-old rats. CONCLUSIONS: Our results suggest the age related difference observed in the testicular response to the oral administration of DEHP may be due to the metabolism, and that oxidative stress may be related to the mechanism of DEHP induced testicular toxicity.

Testicular Toxicity Evaluation of Two Antimony Compounds, Antimony Trioxide and Antimony Potassium Tartrate, in Rats and Mice

Objectives: Testicular toxicities of antimony compounds were evaluated in rats and mice. The slightly water-soluble antimony compound antimony trioxide (ATO) and the highly water-soluble antimony compound antimony potassium tartrate (APT) were examined. Methods: Daily doses of the compounds were 27.4, 12.0 and 1,200 mg/kg body weight in the APT group, low-ATO group and high-ATO group, respectively. The corresponding daily doses of antimony were 10, 10 and 1,000 mg/kg body weight, in the APT group, low-ATO group and high-ATO group, respectively. Both compounds were administered by gavage: rats, 3 days per week for 4 weeks; mice, 5 days per week for 4 weeks. Results: Neither compound reduced the weights of reproductive organs or accessory sex organs nor affected sperm parameters. Few marked histopathologic changes were found in the testes of the treated animals. Even at 1,200 mg/kg body weight, which is greater than the LD50 of APT, ATO produced no effects. Conclusions: In this study, it was found that ATO and APT are not toxic to testes in rodents.

The effects of cyclosporin A on testes of rats / 대한비뇨기과학회지

The goals of the immunosuppressive agent are the development of simple, reproducible means of effecting donor-specific recipient tolerance. For these purposes, cyclosporin A has proved to be effective in supporting engraftment of kidney. heart liver. and bone marrow transplantation. But it has some side effects. Nephrotoxicity and hepatotoxicity are among the more common side effects. Others are the endocrinological side effects, such as hirsutism, gynecomastia, infertility and impotence. This gonadal dysfunction may be 1 the result of defects in the hypothalamic-pituitary-gonadal axis ;2 caused by the direct cytotoxic effects on testis ,or secondary to uremic state. The aim of this study was to evaluate the effects of cyclosporin A on testes of rats, and to study for pathogenesis of gonadal dysfunction by exogenous testosterone administration for the supplement of defected testosterone. 1. In comparison to the control group, body weight was decreased significantly in the other groups. The degree of weight loss in group VII was not significant when compared to group IV 2. The sperm head count was significantly reduced with cyclosporin A administration in all experimental groups that compared with the control group (p0.05). 3. The repopulation index was significantly reduced with cyclosporin A administration in all experimental groups as compared with the control group. The repopulation index in group VII was significant as compared with group W (p<0.05). 4. The LDH-X activities in cytosol of testes were decreased significantly with the administration or cyclosporin A. The activity of LDH-X in group VII did not decrease as much as group IV(p<0.05). The exogenous supplement of testosterone could reduce the toxic effects of cyclosporin A on testes. The results of this experiment suggest that harmful effects of cyclosporin A on testes of rats are due to a defect of hypothalamic-pituitary-gonadal axis.

Protective Effects of Medroxyprogesterone Acetate on Testicular Cytotoxicity of Doxorubicin in Rats / 대한비뇨기과학회지

As the number of long-term survivors is increasing with recent advances of anticancer chemotherapeutics, the late toxic effects of anticancer agents are assuming increased importance. Many young men who have been successfully treated with antineoplastic agents develop azoospermia which persist long after cessation of treatment. Post-pubertal sexual development and spermatogenesis are often unaffected in males who have received chemotherapy before puberty. On the basis of this observation and from animal studies it has been suggested that chemotherapy-induced damage to spermatogenesis can be avoided or at least reduced by the induction of a "resting state" of the testes. This can be achieved by analogues of LH-RH or medroxyprogesterone acetate. The aim of present study was to evaluate protective effect from doxorubicin-induced testicular damage with medroxyprogesterone acetate in rats. 1. Comparing with control group, body weight was not changed in medroxyprogesterone acetate treated group. The rats which received doxorubicin displayed significant weight loss. Body weight was decreased more significantly in group III (doxorubicin only administration) than in group IV (medroxyprogesterone acetate and doxorubicin administrational(p <0.001) 2. Testicular weight was markedly decreased by medroxyprogesterone acetate injection but the weight was increased gradually after cessation of administration. In group III and group IV, testicular weights were also decreased markedly, but there was no difference between two groups(p <0.5 ). 3. Sperm head count was reduced with medroxyprogesterone acetate administration but the count was increased gradually after cessation of administration. In group III and group IV sperm head counts were also decreased but more significantly reduced in group III.( <0.005). 4. Repopulation index was diminished with medroxyprogesterone acetate administration up to medical castration level but repopulation index was returned to nearly normal after cessation of administration. In group III and group IV, repopulation indices were also diminished but more significantly diminished in group III.( p <0.005) With above results we can suggest that temporary interruption of the pituitary gonadal axis with medroxyprogesterone acetate may ameliorate the gonadal toxicity of doxorubicin therapy.