Ovarian damage from chemotherapy and current approaches to its protection

BACKGROUND: Anti-cancer therapy is often a cause of premature ovarian insufficiency and infertility since the ovarian follicle reserve is extremely sensitive to the effects of chemotherapy and radiotherapy. While oocyte, embryo and ovarian cortex cryopreservation can help some women with cancer-induced infertility achieve pregnancy, the development of effective methods to protect ovarian function during chemotherapy would be a significant advantage.OBJECTIVE AND RATIONALE: This paper critically discusses the different damaging effects of the most common chemotherapeutic compounds on the ovary, in particular, the ovarian follicles and the molecular pathways that lead to that damage. The mechanisms through which fertility-protective agents might prevent chemotherapy drug-induced follicle loss are then reviewed.SEARCH METHODS: Articles published in English were searched on PubMed up to March 2019 using the following terms: ovary, fertility preservation, chemotherapy, follicle death, adjuvant therapy, cyclophosphamide, cisplatin, doxorubicin. Inclusion and exclusion criteria were applied to the analysis of the protective agents.OUTCOMES: Recent studies reveal how chemotherapeutic drugs can affect the different cellular components of the ovary, causing rapid depletion of the ovarian follicular reserve. The three most commonly used drugs, cyclophosphamide, cisplatin and doxorubicin, cause premature ovarian insufficiency by inducing death and/or accelerated activation of primordial follicles and increased atresia of growing follicles. They also cause an increase in damage to blood vessels and the stromal compartment and increment inflammation. In the past 20 years, many compounds have been investigated as potential protective agents to counteract these adverse effects. The interactions of recently described fertility-protective agents with these damage pathways are discussed.WIDER IMPLICATIONS: Understanding the mechanisms underlying the action of chemotherapy compounds on the various components of the ovary is essential for the development of efficient and targeted pharmacological therapies that could protect and prolong female fertility. While there are increasing preclinical investigations of potential fertility preserving adjuvants, there remains a lack of approaches that are being developed and tested clinically

Effects of lycopene against cisplatin-induced nephrotoxicity and oxidative stress in rats

The aim of this study was to investigate the effects of lycopene on cisplatin-induced nephrotoxicity and oxidative stress in rats. Adult male Sprague-Dawley rats were randomly divided into four groups. The control group (group 1) received physiological saline; animals in group 2 received only cisplatin; a 10 days of lycopene pre-treatment was applied to the animals in group 3 before administration of cisplatin; a 5 days of lycopene treatment was performed following administration of cisplatin for the animals in group 4. Cisplatin (7 mg/kg) was intraperitoneally injected as a single dose and lycopene (4 mg/kg) was administered by gavage in corn oil. Biochemical and histopathological methods were utilised for evaluation of the nephrotoxicity. The concentrations of creatinine, urea, Na+ and K+ in plasma and levels of malondialdehyde and reduced glutathione as well as glutathione peroxidase and catalase activities were deter-mined in kidney tissue. Administration of cisplatin to rats induced a marked renal failure, characterized with a significant increase in plasma creatinine and urea concentrations. Na+ and K+ levels of rats received cisplatin alone were not significantly different compared to control group, but they had higher kidney malondialdehyde, and lower reduce glutathione concentrations, glutathione peroxidase and catalase activities. Lycopene administration produced amelioration in biochemical indices of nephrotoxicity in both plasma and kidney tissues when compared to group 2; pre-treatment with lycopene being more effective. Results from this study indicate that the novel natural antioxidant lycopene might have protective effect against cisplatin-induced nephrotoxicity and oxidative stress in rat. (c) 2005 Elsevier Ireland Ltd. All rights reserved

Protective effect of lycopene on adriamycin-induced cardiotoxicity and nephrotoxicity

The aim of this study was to investigate the possible protective role of lycopene on adriamycin (ADR)-induced heart and kidney toxicity using biochemical and histopathological approaches. Rats were randomly divided into four groups. The first group received no medication and was regarded as the control group; the second group was injected with a single dose of ADR; the third group was treated with lycopene for 10 days before ADR injection and the last group was treated with lycopene for 2 days before and for 3 days after the administration of a single dose of ADR. ADR (10 mg/kg) was intraperitoneally (i.p.) injected as a single dose and lycopene (4 mg/kg) was administered in corn oil by gavage. The levels of malondialdehyde (MDA) and reduced glutathione (GSH) in both the heart and kidneys were higher in the group treated with ADR alone than in the control group, and were lower in the groups administered with lycopene than in the ADR alone group. Although the activity of catalase (CAT) in the heart was higher in the ADR alone group than in the control group, it was lower in the kidneys. In particular, treatment with lycopene post-injection normalized both cardiac and kidney CAT activities. In heart and kidney tissues, glutathione peroxidase (GSH-Px) activities were not significantly different between all groups. Significant increases in the levels of plasma creatinine and urea were observed in the ADR group when compared to the control group, and these increases were normalized by lycopene treatment. Cardiac and renal histopathological changes were observed in the ADR group as compared to the control group. In contrast, these histopathological changes appeared nearly normal in the groups treated with lycopene pre- and post-injection. In conclusion, this study clearly indicated that ADR treatment markedly impaired cardiac and renal function and that treatment with lycopene might prevent this toxicity in rats. (C) 2005 Published by Elsevier Ireland Ltd

Acute effects of methiocarb on oxidative damage and the protective effects of vitamin E and taurine in the liver and kidney of Wistar rats

Methiocarb (MC) is a widely used carbamate pesticide in agriculture and health programs. Although the main molecular mechanism of carbamate toxicity involves acetylcholinesterase inhibition, studies have also implicated the induction of oxidative stress. Therefore, the present study was aimed to evaluate the effect of acute MC exposure on lipid peroxidation, antioxidant defense systems, histological changes in Wistar rats and the protective effect of pretreatment with vitamin E and taurine. A total of 48 rats were randomly divided into six groups. Rats in group I were given corn oil, while those in group III were dosed with vitamin E (100 mg/kg body weight (b.w.)) and in group V were dosed with taurine (50 mg/kg b.w.). Rats in group II were administered with MC only (25 mg/kg b.w., 1/4 of median lethal dose (LD50)), while those in groups IV and VI were pretreated with vitamin E (100 mg/kg b.w.) and taurine (50 mg/kg b.w.) for 20 days, respectively, and then exposed to MC (25 mg/kg b.w.). The rats administered with MC showed significant increase in the levels of malondialdehyde in the liver and kidney as an index of lipid peroxidation. Levels of glutathione and activities of superoxide dismutase, catalase and glutathione peroxidase were significantly increased, while activity of glutathione reductase remained unchanged in both the tissues after MC treatment. Mild degenerative histological changes were observed in liver tissue, while the changes in kidney tissue were more severe then liver after MC treatment. Pretreatment with vitamin E and taurine resulted in a significant decrease in the lipid peroxidation and alleviating effects on antioxidant defense systems in both the tissues, while protective effects on the histological changes were shown only in kidney when compared with liver. In conclusion, the study has demonstrated that the acute MC exposure in Wistar rats caused oxidative damage on liver and kidney, which were partly ameliorated by the pretreatment of vitamin E and taurine