Cilostazol protects against cyclophosphamide-induced ovarian toxicity in female rats: role of cAMP and HO-1

Abdel-Aziz, Asmaa Mohamed; mohamed, ahmed; Abdelazem, Osama; Okasha, Ahmed M; Kamel, Maha Yehia

doi:10.1080/15376516.2020.1774829

Cited by 18 publications

(13 citation statements)

References 47 publications

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“…77,78 Different chemotherapeutic drugs have been reported to cause this condition as a negative side effect. 77,79–81 Previous experiments showed that after intraperitoneal administration of 50 mg/kg/day 5FU for 4 days, the ovarian size was remarkably diminished compared to the control group (Table 3). 8 In another research, 5FU caused significant reduction of body weight and ovarian wet weight to body weight ratio in female rats.…”

Section: Fu-induced Female Reproductive Toxicitymentioning

confidence: 96%

5-Fluorouracil-induced toxicity in both male and female reproductive systems: A narrative review

Pirzaman,

Ebrahimi,

Doostmohamadian

et al. 2023

Hum Exp Toxicol

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The chemotherapeutic drug 5-fluorouracil (5FU) is frequently used to treat a wide range of solid malignant tumors, such as colorectal, pancreatic, gastric, breast, and head and neck cancers. Its antitumoral effects are achieved by interfering with the synthesis of RNA and DNA and by inhibiting thymidylate synthase in both malignant and non-malignant cells. Therefore, it can be responsible for severe toxicities in crucial body organs, including heart, liver, kidney, and reproductive system. Given the fact that 5FU-induced reproductive toxicity may limit the clinical application of this drug, in this study, we aimed to discuss the main locations and mechanisms of the 5FU-induced reproductive toxicity. Initially, we discussed the impact of 5FU on the male reproductive system, which leads to damage of the seminiferous epithelial cells and the development of vacuoles in Sertoli cells. Although no noticeable changes occur at the histopathological level, there is a decrease in the weight of the prostate. Additionally, 5FU causes significant abnormalities in spermatogenesis, including germ cell shedding, spermatid halo formation, polynucleated giant cells, and decreased sperm count. Finally, in females, 5FU-induced reproductive toxicity is characterized by the presence of atretic secondary and antral follicles with reduced numbers of growing follicles, ovarian weight, and maturity impairment.

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Section: Fu-induced Female Reproductive Toxicitymentioning

confidence: 96%

5-Fluorouracil-induced toxicity in both male and female reproductive systems: A narrative review

Pirzaman,

Ebrahimi,

Doostmohamadian

et al. 2023

Hum Exp Toxicol

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“…Excess of NO decreased progesterone synthesis and promoted apoptotic cell death in rat granulose cells. [ 71 ] Increased in levels of NO reflected inflammatory response. Furthermore, NO produced in human granulosa luteal cells seemed to decrease estradiol release by inhibiting the aromatase enzymatic activity.…”

Section: Cyclophosphamidementioning

confidence: 99%

“…Histopathological and immunohistochemical investigation revealed ovarian vascular congestion, hemorrhage, leukocyte infiltration, ovarian stromal edema, corpus luteum degeneration, and follicular atresia after in vivo CPA treatment. [ 71 ] In addition, it causes morphological alterations in growing follicles marked by abnormal follicular structures with damaged vasculature and inflammation. [ 69 ] An acute exposure to PM adversely effected granulosa cell viability and resulted in irreversible loss of growing follicles.…”

Section: Cyclophosphamidementioning

confidence: 99%

“…A histological study has revealed the loss of numerous follicles after CPA administration associated with altered antioxidant enzyme activity, indicating oxidative stress‐induced follicular atresia. [ 71 ] Caspase‐3 immunohistochemistry elucidated extensive cytoplasmic immune‐reactivity in the ovarian tissue. As a result of granulosa cell death or proliferation suppression, there is a decrease in follicular number and an increase in follicular atresia.…”

Section: Cyclophosphamidementioning

confidence: 99%

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Chemotherapeutic drugs induced female reproductive toxicity and treatment strategies

Bhardwaj

Bikal

Sachdeva

2023

J Biochem & Molecular Tox

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Increase in success of cancer treatment with advancement in the screening, prognosis and diagnosis protocols have significantly improved the rate of cancer survivorship. With the declining cancer mortality, however, the cancer survivors are also subjected to the adverse consequences of chemotherapy, particularly in the female reproductive system. Recent studies have shown the sensitivity of the ovarian tissue to the chemotherapeutic drugs‐induced toxicity. Several in vitro and in vivo studies have assessed the toxic effects of chemotherapeutic drugs. The most frequently used chemotherapeutic drugs such as doxorubicin, cyclophosphamide, cisplatin and paclitaxel have been reported to cause ovarian damage, diminution of follicular pool reserve, premature ovarian failure and early menopause, resulting into declining fertility potential among females. The chemotherapy often employs combination of drug regimen to increase the efficacy of the treatment. However, the literature mostly consists of clinical data regarding the gonadotoxicity caused by anticancer drugs but there lacks the understanding of toxicity mechanism. Therefore, understanding of the different toxicity mechanisms will be helpful in development of possible therapeutic interventions for preservation of declining female fertility among cancer survivors. The current review comprehends the underlying mechanisms of female reproductive toxicity induced by the most commonly used chemotherapeutic drugs. In addition, the review also summarizes the recent findings related to the use of various protectants to diminish or at least in managing the toxicity induced by different chemotherapeutic drugs in females.

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“…Reactive Oxygen Species (ROS) production impairs ovarian antioxidant defenses, as well as lipid peroxidation and mitochondrial injury, resulting in caspase activation and ovarian follicle apoptosiss [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Empagliflozin Protects against Haloperidol Experimentally-Induced Ovarian Toxicity

et al. 2023

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The present experiment aimed to identify the potential protective role of empagliflozin (EMPA) on haloperidol (HAL)-induced ovarian damage in female rats because of its anti-inflammatory, antioxidant, and antiapoptotic effects. EMPA was administered in the presence and absence of HAL. Thirty-two adult female albino rats were divided into four groups. Control group, EMPA group: received EMPA (10 mg/kg/day) p.o., HAL group: received HAL (2 mg/kg/day) p.o., HAL + EMPA group: HAL (2 mg/kg/day) combined with EMPA for 28 days. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-mullerian hormone (AMH) levels were measured. Ovarian oxidative stress parameters, besides inflammatory and apoptotic biomarkers, and ovarian Sirtuin-1 (Sirt-1) were evaluated. Ovarian histopathological examination and heat shock protein 70 (Hsp70) immunohistochemical study were performed. HAL significantly increased serum levels of FSH, LH, and ovarian inflammatory, apoptotic, and oxidative stress biomarkers and decreased serum AMH levels and Sirt-1 expression. Histopathological findings of ovarian damage and high Hsp70 immunoexpression were detected. EMPA significantly normalized the distributed hormonal levels, oxidative stress, inflammatory, and apoptotic biomarkers with a prompt improvement in the histopathological picture and a decrease in Hsp70 immunoexpression. Accordingly, EMPA protected against HAL-induced ovarian toxicity by modulating the Sirt-1/Hsp70/TNF-α/caspase-3 signaling pathway.

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Cilostazol protects against cyclophosphamide-induced ovarian toxicity in female rats: role of cAMP and HO-1

Cited by 18 publications

References 47 publications

5-Fluorouracil-induced toxicity in both male and female reproductive systems: A narrative review

5-Fluorouracil-induced toxicity in both male and female reproductive systems: A narrative review

Chemotherapeutic drugs induced female reproductive toxicity and treatment strategies

Empagliflozin Protects against Haloperidol Experimentally-Induced Ovarian Toxicity

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