First evidence of the protective role of melatonin in counteracting cadmium toxicity in the rat ovary via the mTOR pathway

• Published in: Environmental pollution (1987) Vol. 270; p. 116056
• Main Authors: Kechiche, Safa, Venditti, Massimo, Knani, Latifa, Jabłońska, Karolina, Dzięgiel, Piotr, Messaoudi, Imed, Reiter, Russel J., Minucci, Sergio
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-02-2021
• Subjects: Animals; Autophagy; Cadmium - metabolism; Cadmium - toxicity; Endocrine disruptor; Female; Melatonin; Melatonin - metabolism; Melatonin - pharmacology; mTOR pathway; Ovary - metabolism; Oxidative Stress; Rats; TOR Serine-Threonine Kinases - metabolism; mTOR pathway; Oxidative stress; Melatonin; Endocrine disruptor; Autophagy; Cadmium toxicity
• ISSN: 0269-7491; 1873-6424
• DOI: 10.1016/j.envpol.2020.116056

Herein, the first evidence of the ability of melatonin (MLT) to counteract cadmium (Cd) toxic effects on the rat ovary is reported. Cd treatment, enhancing oxidative stress, provoked clear morphological, histological and biomolecular alterations, i.e. in the estrous cycle duration, in the ovarian and serum E2 concentration other than in the steroidogenic and folliculogenic genes expression. Results demonstrated that the use of MLT, in combination with Cd, avoided the changes, strongly suggesting that it is an efficient antioxidant for preventing oxidative stress in the rat ovary. Moreover, to explore the underlying mechanism involved, at molecular level, in the effects of Cd-MLT interaction, the study focused on the mTOR and ERK1/2 pathways. Interestingly, data showed that Cd influenced the phosphorylation status of mTOR, of its downstream effectors and of ERK1/2, inducing autophagy and apoptosis, while cotreatment with MLT nullified these changes. This work highlights the beneficial role exerted by MLT in preventing Cd-induced toxicity in the rat ovary, encouraging further studies to confirm its action on human ovarian health with the aim to use this indolamine to ameliorate oocyte quality in women with fertility disorders.
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•Cadmium induces oxidative stress, reducing SOD and CAT activity in the rat ovary.•Cadmium acts on morphology and biochemical parameters, altering ovarian physiology.•Cadmium toxicity acts via mTOR pathway, leading to autophagy.•Melatonin, as antioxidant, prevents the cadmium toxicity.•Melatonin can be used to improve oocyte quality in women with fertility disorders.
Cadmium toxicity enhances oxidative stress in the rat ovary, altering its physiology. Melatonin protects against these effects, acting on antioxidant defenses.