Cisplatin-Induced Germ Cell Apoptosis in Mouse Testes

Zhang, X.; Yamamoto, Naoyuki; Soramoto, S.; Takenaka, Ikumasa

doi:10.1080/01485010150211146

Cited by 50 publications

(44 citation statements)

References 20 publications

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“…Mathews [54] reported that the damage occurred in the cell membrane by hydroxyl radicals induced oxidation. This could also explain the marked degeneration, atrophied ovary and decrease number of viable follicles reported in this study which are in line with several reports [23,25,[55][56][57].…”

Section: The Biochemical Effectssupporting

confidence: 82%

Cisplatin-Induced Ovarian Cytotoxicity and the Modulating Role of Aqueous Zest Extract of Citrus limonium (AZECL) in Rat Models

Gg¹,

Oa²,

Uk³

et al. 2017

J Tradi Med Clin Natur

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Cisplatin is a prominent member of the effective broad-spectrum antitumor drugs. However, its clinical usage is restricted due to some adverse side effects, such as testiculototoxicity, hepatotoxicity and nephrotoxicity. The aim of this study is to evaluate the effect of Aqueous Zest Extract of Citrus limonium (AZECL) on the ovary of female Wistar rat treated with Cisplatin. Twenty adult female Wistar rats were divided into four groups (A-D) containing five rats each. Group A rats served as negative control and were treated orally with 2.5 ml/kg body weight of normal saline, group B rats served as positive control group and were treated intraperitoneally with a single dose of 10 mg/kg body weight of Cisplatin, group C rats were treated orally with 50 mg/kg body weight of AZECL and group D rats were treated intraperitoneally with a single dose of 10 mg/kg body weight of Cisplatin and two weeks later treated orally with 50 mg/kg body weight of AZECL. Result showed a significant (p<0.01) decrease in primary follicles, secondary follicles, graafian follicles and a significant (p<0.01) increase in atretic follicles, PAS positive reaction and reduction in the total carbohydrate contents of the stromal cells in the positive control group. Also there was a significant (p<0.05) decrease in the activity level of FSH, LH and a significant (p<0.05) increase in Malondialdehyde when compared to rats in group A and C. The group post-treated with the extract had remarkable normalization of the histo-morphometric, histochemical and biochemical parameters when compared to the positive control group. Aqueous zests extract of C. limonium has a curative effect on cisplatin-induced cytotoxicity on the ovary.

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Section: The Biochemical Effectssupporting

confidence: 82%

Cisplatin-Induced Ovarian Cytotoxicity and the Modulating Role of Aqueous Zest Extract of Citrus limonium (AZECL) in Rat Models

Gg¹,

Oa²,

Uk³

et al. 2017

J Tradi Med Clin Natur

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“…Experimental studies have reported that germ cell apoptosis is induced by treatment with cisplatin (9). The anti-apoptotic effect(s) of carnitine in the testes may also contribute to this apoptosis, but such an effect remains speculative and requires further investigation.…”

Section: Introductionmentioning

confidence: 99%

“…Gonadotoxicity is one of the most important dose-limiting side effects (4)(5)(6)(7). It directly affects the spermatogonia, inhibiting spermatogenesis or impairing the cellular functions of Sertoli cells, which leads to permanent infertility (8)(9)(10). Therefore, it has become important to supplement with antioxidants to reduce the damage created by anti-tumoural drugs (11).…”

Section: Introductionmentioning

confidence: 99%

The Protective Effects of Acetyl L-Carnitine on Testis Gonadotoxicity Induced by Cisplatin in Rats

Coşkun¹,

Hatipoğlu²,

Özoğul³

et al. 2013

Balkan Med J

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Background: Cisplatin, an effective antineoplastic agent, damages normal cells in a manner related to chemotherapy. Acetyl L-carnitine protects cells against mitochondrial and nuclear damage induced by chemotherapy. Aims: Animal experimentStudy Design: The aim of this study was to examine the protective effects of acetyl L-carnitine on cisplatin-induced gonadotoxicity in testicular structures. Twenty-four male Wistar albino rats were divided into four Groups (n=6): Group 1 (control) was administered saline; Group 2 was administered acetyl Lcarnitine; Group 3 was administered cisplatin; and Group 4 was pre-treated with acetyl L-carnitine before cisplatin administration.Methods: After 72hr of treatment with cisplatin, the rats were sacrificed, and the testicular tissues were removed. Morphometric, histomorphologic and immunohistochemical analyses were conducted.Results: At the end of the experiment, Group 3 was characterised by statistically significant weight loss, a degenerative appearance of the seminiferous tubules in the peripheral region, separation of spermatogenic cell series from the tubular wall, cellular debris in the lumen and central interstitial oedema. Sperm morphology appeared to be abnormal. Tubular diameter and wall thickness decreased, and the number of TUNEL-and active caspase-positive cells increased compared with the other Groups. The histological findings in Group 4 were better than those in Group 3. Conclusion:It was concluded that the prophylactic use of acetyl L-carnitine protects against cisplatin-induced testicular tissue damage.

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“…In male rats there is evidence that cisplatin induces apoptosis in the germ cells, early spermatocytes, and spermatogonia. 36,37 Amifostine, another FDA approved drug used to reduce systemic side effects of chemotherapy, has been demonstrated to reduce the levels of apoptosis in the rat testis.…”

Section: 27-29mentioning

confidence: 99%

Reproductive Toxic Effects of Cisplatin and Its Modulation by the Antioxidant Sodium 2-Mercaptoethanesulfonate (Mesna) in Female Rats

Yeh¹,

Kim²,

Peresie³

2011

Reproductive Biology Insights

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Study Objective: Chemical protection against cisplatin, which is a commonly used cancer chemotherapeutic agent, is not well defined. We tested the hypothesis that the antioxidant mesna might protect against the cisplatin-induced repoductive effects in female rats. Design & Setting: Adult female rats were injected with saline, cisplatin alone, or mesna + cisplatin, mated with males, and euthanized on gestational day 17. Patients: Animal Model. Interventions: The administration of either cisplatin or mesna + cisplatin (two injections one week apart, mesna 30 minute pretreatment) followed by mating one week after treatment. Main Outcomes Measured:The number corpora lutea, implantation and resorptions sites, viable and non-viable fetuses, fetal weights, and the level of progesterone per corpus luteum. Results: The administration of cisplatin caused an increase in pre-and post-implantation loss, an increase in the number of resorptions and a decrease in the number of viable fetuses. Mesna administered prior to cisplatin resulted in a decrease in the rate of the pre-and post implantation loss, along with a decrease in the number of resorptions and an increase in the number of live fetuses. Conclusions: Prior exposure to cisplatin caused significant adverse effects on fertility as evidenced by the decreased implantation due to increased fetal loss. The administration of mesna appeared to temper cisplatin damage by lessening the cisplatin effects on fetal resorption.

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Cisplatin-Induced Germ Cell Apoptosis in Mouse Testes

Cited by 50 publications

References 20 publications

Cisplatin-Induced Ovarian Cytotoxicity and the Modulating Role of Aqueous Zest Extract of Citrus limonium (AZECL) in Rat Models

Cisplatin-Induced Ovarian Cytotoxicity and the Modulating Role of Aqueous Zest Extract of Citrus limonium (AZECL) in Rat Models

The Protective Effects of Acetyl L-Carnitine on Testis Gonadotoxicity Induced by Cisplatin in Rats

Reproductive Toxic Effects of Cisplatin and Its Modulation by the Antioxidant Sodium 2-Mercaptoethanesulfonate (Mesna) in Female Rats

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