The Ameliorative Effects of L-Carnitine against Cisplatin-Induced Gonadal Toxicity in Rats

Cisplatin (CP) is a highly efficient remedy in cancer treatment, but it adversely affects the testicular tissue. This work assessed the ameliorative efficacy of Lcarnitine (LC) against CP induced oxidative stress in rat testis, via investigating testosterone level and tissue oxidative/antioxidant parameters, histological alterations, and immunohistochemical expressions of intermediate filaments (IFs) proteins; vimentin (VIM) and cytokeratin 18 (CK18). Twenty-eight rats were assigned into four groups (7 rats each) as follows; groups I and II received saline and LC (100 mg/kg b.wt.) respectively orally once daily for 30 days; group III were injected with a single dose of CP (7.5 mg/kg, IP), 27 days after starting the experiment. Group IV received both LC and CP. Injection of CP significantly decreased serum testosterone and glutathione reductase and catalase in the testicular tissues and elevated malondialdehyde. Histologically, testes of the CP treated group revealed marked degenerative changes. Also, overexpression of both VIM and CK18 in testicular tissues were recorded. However, the administration of LC with CP restored the biochemical parameters, histological and immunohistochemical pictures towards the normalcy. Accordingly, LC is recommended as a supplement with chemotherapy to ameliorate its oxidative stress. This is the first study investigating the immunohistochemical expressions of IFs proteins, VIM and CK18, following administration of LC as a protective agent against CP induced testicular toxicity in rats

AN UPDATE ON TOXICITY OF THERAPEUTIC RADIONUCLIDES

Targeted radiotherapy is an evolving and promising modality of cancer treatment. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. A number of radionuclides, such as iodine-131 (131I), phosphorus-32 (32P), strontium-90 (90Sr), and yttrium-90 (90Y), have been used successfully for the treatment of many benign and malignant disorders. The toxicity to radionuclides has come into vogue with its increasing utilization for multiple indications. Short term hematological toxicities include cytopenias and long term hematological toxicities include myeloid neoplasms. Non hematological toxicities commonly include renal and hepatotoxicity and long term toxicities like gonadal toxicity. This review focuses on the toxicities which need to be monitored during use of therapeutic radionuclides.

Knowledge of iatrogenic premature ovarian insufficiency among Chinese obstetricians and gynaecologists: a national questionnaire survey

Background With increasing cases of iatrogenic premature ovarian insufficiency (POI), more clinicians are required to counsel patients regarding the gonadotoxic effects of iatrogenic treatments. This survey aimed to explore obstetricians and gynaecologists’ knowledge regarding iatrogenic POI. A national online questionnaire survey was conducted across China. Respondents were asked to select the iatrogenic condition(s) that can cause POI based on their experience and knowledge. Results Of the 5523 returned questionnaires, 4995 were analysed. Among tumour therapies causing POI, most respondents agreed that radiotherapy (73.5% of respondents) and chemotherapy (64.1%) are risk factors for POI. While only 6.5 and 7.8% of the gynaecological oncologists believed that tumour immunotherapy and tumour-targeting therapy, respectively, may cause ovarian impairment, 31.8 and 22.2% of the non-gynaecologic oncologists believed that these therapies could affect ovarian health. Most respondents believed that ovarian cystectomy (54.4%) was a risk factor for POI. In contrast, only a few respondents believed that hysterectomy with bilateral salpingectomy (39.6%) and uterine artery embolisation (33.5%) could cause ovarian impairment. Only 30.5% of respondents believed that immunosuppressants (ISs) increased the risk of POI. Views differed with experience and hospital setting. Conclusions The knowledge of gonadal toxicity due to traditional tumour treatments is generally high among Chinese obstetricians and gynaecologists. A misunderstanding may exist in primary care hospitals and general gynaecologists regarding a link between novel tumour treatments and POI, owing to the lack of convincing evidence. Knowledge of POI caused by hysterectomy and ISs should be improved.

Effects of Maternal Exposure to Lamotrigine during Pregnancy on Gonadal Toxicity in Fetus Rats

Background: Lamotrigine is one of the newest antiepileptic drugs that is used as one of the most common treatments in pregnancy. Since the investigation of the teratogenic effects of lamotrigine is very limited and there is no report of its teratogenic effects on fetal gonads, we aimed to investigate the teratogenic effects of lamotrigine on embryonic gonads. Materials and Methods: This study was performed on nine female Wistar female rats (8 weeks, weighing 180-200 mg). At first, the animals were inspected regularly by the preparation of vaginal smear and in the estrus phase in separate cages of mating, and after observing the vaginal plaque, were randomly divided into three groups (n=3). Control group did not receive any treatment. In the lamotrigine group (20mg/kg), and the vehicle group (same volume of normal saline) were injected intraperitoneally from days 8 to 13 of pregnancy. On day 20, animals were anesthetized by sodium pentobarbital (40 mg/kg), and embryos were extracted through laparotomy. First, fetuses were weighed, and their height (crown-rump length) was measured. Then the gonads of the fetuses were removed and, stained with H & E, and examined by optical microscope. Results: Our results showed that in the lamotrigine group, the number of seminiferous tubules and Sertoli cells in the male embryos and the number of oocytes in the female embryos decreased significantly compared to the control and vehicle groups (P≤0.05). Conclusion: The results of this study showed that treatment with 20 mg/kg lamotrigine in mothers during pregnancy could cause damage to fetal gonads. [GMJ.2020;9:e1557]

Knowledge of Iatrogenic Premature Ovarian Insufficiency Among Chinese Obstetricians and Gynecologists: A National Questionnaire Survey

Background: With increasing cases of iatrogenic premature ovarian insufficiency (POI), more clinicians are required to counsel patients regarding the gonadotoxic effects of iatrogenic treatments. This survey aims to explore obstetricians and gynecologists’ knowledge regarding iatrogenic POI. A national online questionnaire survey was conducted across China. Respondents were asked to select the iatrogenic condition(s) that can cause POI based on their experience and knowledge.Results: Of the 5,523 returned questionnaires, 4,995 were analyzed. Among tumor therapies causing POI, most respondents agreed that radiotherapy (73.5% of respondents) and chemotherapy (64.1%) are risk factors for POI. While only 6.5% and 7.8% of the gynecological oncologists believed tumor immunotherapy and tumor-targeting therapy, respectively, may cause ovarian impairment, 31.8% and 22.2% of the non-gynecologic oncologists believed that these therapies could affect ovarian health. Most respondents believed that ovarian cystectomy (54.4%) was a risk factor for POI, while only a few respondents believed that hysterectomy with bilateral salpingectomy (39.6%) and uterine artery embolization (33.5%) could cause ovarian impairment. Only 30.5% respondents believed that immunosuppressants increased the risk of POI. Views differed with experience and hospital setting.Conclusions: The knowledge of gonadal toxicity due to traditional tumor treatments is generally high among Chinese obstetricians and gynecologists. A misunderstanding may exist in primary care hospitals and general gynecologists regarding a link between novel tumor treatments and POI, owing to the lack of convincing evidence. Knowledge of POI caused by hysterectomy and immunosuppressants should be improved.

Safety Profile and Toxicity Amelioration Strategies of Common Adverse Effects Associated with Anticancer Medications

More than half the cancer patients undergoing cancer chemotherapy develop adverse drug reactions (ADRs). Cancer chemotherapeutic agents have a lower risk-benefit ratio than other drug therapy and kill cancerous as well as the normal rapidly dividing cells including bone marrow cells, gastrointestinal epithelium, hair follicles, etc. Their main ADRs are nausea and vomiting, mucositis, constipation, diarrhea, hematological toxicities, cardiac toxicity, alopecia, gonadal toxicity, pulmonary toxicity, neurotoxicity, nephrotoxicity, etc. The severity of the adverse effects may range from mild nausea to life-threatening neutropenia. Administering premedication and antidotes are very vital in these patients. Upon the occurrence of adverse effects, immediate steps should be taken to manage them. Though the ADRs due to anticancer medications are not avoidable, careful monitoring of the patients and modulating the drug schedules/dosages can help in minimizing them. Healthcare professionals should also develop strategies to minimize the occupational hazards associated with these drugs.

Preservation of fertility in patients with hematological malignancies

Oncofertility is the medical field that bridges oncology and reproduction that seeks to give healthcare providers and patients the opportunity to optimize residual fertility. The treatment for hematological malignancies carries gonadal toxicity, so that the preservation of fertility should be considered in all patients in childhood, adolescence and young adulthood. Most patients who receive only chemotherapy remain fertile, whereas those who receive regimens consisting of high-dose alkylating agents or total body irradiation can develop permanent infertility. In postpubertal patients, there are established methods for preserving fertility, such as the cryopreservation of sperm, oocytes and embryos. Although ideally performed before the initiation of gonadotoxic treatment, these procedures for fertility preservation can be performed any time prior to the loss of gonadal function. In contrast, a standard option is not available in prepubertal patients, and the preservation of fertility must be sought through experimental methods. Future advances in reproductive medicine may overcome this limitation. Gonadal tissue cryopreservation might be performed in the hope that sperm or mature oocytes could later be extracted from cryopreserved tissue. Healthcare providers, including hematologists, reproductive endocrinologists, nurses, clinical psychotherapists and embryologists, need to optimize the patient’s fertility through shared decision-making while always remaining aware of the rapidly progressing developments in reproductive medicine.