RESUMEN
RESEARCH QUESTION: Can melatonin provide non-invasive ovarian protection against damage caused by cis-diamminedichloroplatinum (cisplatin) and preserve fertility in female cancer patients? And if so, what is the possible mechanism? DESIGN: Athymic BALB/c nude tumour-bearing female mice were used to demonstrate whether melatonin affects the antineoplastic effect when co-administrated with cisplatin. Sexually mature and newborn C57BL/6 female mice were used to evaluate the potential effects of melatonin on the ovarian follicle pool, pregnancy rate and litter number in cisplatin-treated mice. The ovaries underwent immunohistochemical, TdT (terminal deoxynucleotidyl transferase)-mediated dUTP nick-end labelling (TUNEL) and gene array analysis to explore the underlying mechanism. In addition, granulosa cells were isolated to investigate the potential protective mechanism of melatonin. RESULTS: Melatonin not only enhanced the anti-cancer effect of cisplatin in tumour-bearing nude mice, but also reduced ovarian toxicity and preserved long-term fertility in cisplatin-treated C57BL/6 female mice. When co-administrated, melatonin was able to reduce the DNA damage and toxic effects on lipid peroxidation in the ovaries caused by cisplatin. Specifically, melatonin was able to largely restore lipid peroxidation in granulosa cells and thus prevent ovarian follicles from being depleted. CONCLUSIONS: Melatonin has the potential to be used as a chemotherapeutic adjuvant to simultaneously improve the outcome of anti-cancer treatment and preserve ovarian function during cisplatin chemotherapy. Notably, its properties of DNA protection and antioxidant effects on follicles may benefit female cancer survivors and prevent premature ovarian failure as well as fertility loss caused by chemotherapy.
Asunto(s)
Antineoplásicos/efectos adversos , Antioxidantes/uso terapéutico , Cisplatino/efectos adversos , Infertilidad Femenina/prevención & control , Melatonina/uso terapéutico , Ovario/efectos de los fármacos , Animales , Animales Recién Nacidos , Evaluación Preclínica de Medicamentos , Femenino , Infertilidad Femenina/inducido químicamente , Ratones DesnudosRESUMEN
Alzheimer's disease (AD) is characterized by the cholinergic neurons loss and impairments of learning and memory. Scopolamine is common used to imitate AD pathological features and also causes an obvious oxidative stress. In this study, we found that intraperitoneal administration of supplementary acetyl-L-carnitine partially reverses the learning and memory defects induced by scopolamine. We also found that acetyl-L-carnitine reverses the impairment of long-term potentiation, dendritic abnormalities, and the impaired recruitment of synaptic protein. The beneficial effects of acetyl-L-carnitine may occur through amelioration of oxidative stress because it effectively decreases the levels of oxidative products and increases the activity of superoxide dismutase; this leads to a recovery in the suppressed activity of p53 caused oxidative stimuli, which in turn restores levels of insulin-like growth factor II, an important hormone for learning and memory. Our study provides the first evidence of the potential utility of acetyl-L-carnitine in treating the synaptic disorders prevalent in AD and other neurodegenerative diseases. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.