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

Kechiche, Safa; Venditti, Massimo; Knani, Latifa; Jabłońska, Karolina; Dzięgiel, Piotr; Messaoudi, Imed; Reíter, Russel J.; Minucci, Sergio

doi:10.1016/j.envpol.2020.116056

Cited by 32 publications

(24 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since exposure to Cd is unavoidable beyond to expand upon the knowledge concerning its induced reprotoxicity, it is significant to explore strategies that may prevent, alleviate, or counteract Cd effects. In this regard, we previously demonstrated that MLT is capable of counteracting Cd-induced toxicity in rat bone [ 21 ] and ovary [ 22 ], especially because of its antioxidant properties [ 28 ]. To our knowledge, very few papers explored the beneficial role of MLT against testicular Cd toxicity [ 41 , 42 , 43 , 44 , 45 ]; here, we further confirmed the antioxidant and antiapoptotic action of MLT, also documenting the ameliorative effect of MLT on other parameters that have never been analyzed before, i.e., the protein level of steroidogenic enzymes and the expression of the cytoskeleton-associated proteins DAAM1 and PREP.…”

Section: Discussionmentioning

confidence: 99%

“…Groups 1 and 2 received an equivalent amount of ethanol in drinking water. The used concentration of Cd and MLT were chosen according to literature [ 21 , 22 , 30 ]. To protect MLT from light, water bottles were changed twice weekly and covered with aluminum foil.…”

Section: Methodsmentioning

confidence: 99%

“…Considering the remarkable effect of Cd on male fertility, many papers reported the importance of substances that may prevent, counteract, or ameliorate its toxicity to preserve a proper gamete production. Recently, among them, we focused our attention on zinc [ 19 , 20 ] and melatonin (MLT), evaluating their counteractive effects not only in the testis, but also in other tissues targeted by Cd toxicity, such as bone [ 21 ] and ovary [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Altered Expression of DAAM1 and PREP Induced by Cadmium Toxicity Is Counteracted by Melatonin in the Rat Testis

Venditti

Rhouma

Romano

et al. 2021

Genes

Self Cite

View full text Add to dashboard Cite

Cadmium (Cd) is one of the most toxic pollutants for health due to its accumulation in several tissues, including testis. This report confirms that Cd increased oxidative stress and apoptosis of germ and somatic cells and provoked testicular injury, as documented by biomolecular and histological alterations, i.e., CAT and SOD activity, the protein level of steroidogenic enzymes (StAR and 3β-HSD), and morphometric parameters. Additionally, it further documents the melatonin (MLT) coadministration produces affects in mitigating Cd-induced toxicity on adult rat testis, as demonstrated by the reduction of oxidative stress and apoptosis, with reversal of the observed histological changes; moreover, a role of MLT in partially restoring steroidogenic enzymes expression was evidenced. Importantly, the cytoarchitecture of testicular cells was perturbed by Cd exposure, as highlighted by impairment of the expression and localization of two cytoskeleton-associated proteins DAAM1 and PREP, which are involved in the germ cells’ differentiation into spermatozoa, altering the normal spermatogenesis. Here, for the first time, we found that the co-treatment with MLT attenuated the Cd-induced toxicity on the testicular DAAM1 and PREP expression. The combined findings provide additional clues about a protective effect of MLT against Cd-induced testicular toxicity by acting on DAAM1 and PREP expression, encouraging further studies to prove its effectiveness in human health.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Altered Expression of DAAM1 and PREP Induced by Cadmium Toxicity Is Counteracted by Melatonin in the Rat Testis

Venditti

Rhouma

Romano

et al. 2021

Genes

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is well known that the destruction of reproductive organs by environmental pollutants can cause individual reproductive dysfunction. Ovary, as a crucial part of the female reproductive system, its function to maintain fertility was inhibited by environmental pollutants 36,37 . Exposure of mice to 50 mg/kg/d melamine for 56 days impaired the normal growth and development of oocytes and induced infertility 23 .…”

Section: Discussionmentioning

confidence: 99%

Melamine induced changes in histopathology of the main organs and transcriptional levels of MAPK signaling genes in kidneys of female mice

Yang

Liang

Zhang

et al. 2021

Environmental Toxicology

View full text Add to dashboard Cite

Melamine is an important chemical raw material used in industries, which has potential health risks to animals and humans. Current research mainly focuses on the toxic effects of high‐dose melamine ingestion. However, there are few reports on whether melamine at the current limited standard dose has adverse effects on various tissues and organs, and whether there are sensitive target genes for risk evaluation. For this, 24 female Kunming mice were fed 0, 1.8‐, 3.6‐, and 7.2‐ mg/kg/d melamine via drinking water for consecutive 28 days, respectively. The morphological changes of the ovarian, hepatic, and renal tissues were firstly observed. The results demonstrated that the histopathology of ovary, liver, and especially in kidney had been altered by melamine intake in female. And then, the transcriptional levels of MAPK signaling genes including p38, ERK1, ERK2, JNK1, and JNK2 in kidneys were investigated by real‐time PCR. The data showed that ERK1 and p38 mRNAs expressions were up‐regulated significantly by melamine, suggesting that ERK1 and p38 transcriptional levels in the kidney might to be considered as candidate targets for lower‐dose melamine toxicity. This study not only provides potential targets for the diagnosis and prevention of melamine damage, but also helps to assess the health risks of the current minimum allowable levels of melamine in food and environment.

show abstract

“…For the first time (2001), Leung et al found that melatonin via the MAPK pathway regulates progesterone production, LH receptor, GnRH, and GnRH receptor gene expression in human granulosa-luteal cells, which play a direct role in regulating ovarian function (69). Furthermore, melatonin has been shown to enhance follicle growth and proliferation in cadmium-induced injury in rat ovaries via the ERK1/2 and mTOR pathways (70). As the primary female sex hormones, estrogens are responsible for maturing and maintaining the female reproductive system and are also involved in gonadotropin secretion and ovarian follicle maturation.…”

Section: Melatonin's Eight Hub Targets In Dormentioning

confidence: 99%

Melatonin: Multi-Target Mechanism Against Diminished Ovarian Reserve Based on Network Pharmacology

Yang

Chen

et al. 2021

Front. Endocrinol.

View full text Add to dashboard Cite

BackgroundDiminished ovarian reserve (DOR) significantly increases the risk of female infertility and contributes to reproductive technology failure. Recently, the role of melatonin in improving ovarian reserve (OR) has attracted widespread attention. However, details on the pharmacological targets and mechanisms of melatonin-improved OR remain unclear.ObjectiveA systems pharmacology strategy was proposed to elucidate the potential therapeutic mechanism of melatonin on DOR at the molecular, pathway, and network levels.MethodsThe systems pharmacological approach consisted of target identification, data integration, network construction, bioinformatics analysis, and molecular docking.ResultsFrom the molecular perspective, 26 potential therapeutic targets were identified. They participate in biological processes related to DOR development, such as reproductive structure development, epithelial cell proliferation, extrinsic apoptotic signaling pathway, PI3K signaling, among others. Eight hub targets (MAPK1, AKT1, EGFR, HRAS, SRC, ESR1, AR, and ALB) were identified. From the pathway level, 17 significant pathways, including the PI3K-Akt signaling pathway and the estrogen signaling pathway, were identified. In addition, the 17 signaling pathways interacted with the 26 potential therapeutic targets to form 4 functional modules. From the network point of view, by regulating five target subnetworks (aging, cell growth and death, development and regeneration, endocrine and immune systems), melatonin could exhibit anti-aging, anti-apoptosis, endocrine, and immune system regulation effects. The molecular docking results showed that melatonin bound well to all hub targets.ConclusionThis study systematically and intuitively illustrated the possible pharmacological mechanisms of OR improvement by melatonin through anti-aging, anti-apoptosis, endocrine, and immune system regulation effects.

show abstract

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

Cited by 32 publications

References 101 publications

Altered Expression of DAAM1 and PREP Induced by Cadmium Toxicity Is Counteracted by Melatonin in the Rat Testis

Altered Expression of DAAM1 and PREP Induced by Cadmium Toxicity Is Counteracted by Melatonin in the Rat Testis

Melamine induced changes in histopathology of the main organs and transcriptional levels of MAPK signaling genes in kidneys of female mice

Melatonin: Multi-Target Mechanism Against Diminished Ovarian Reserve Based on Network Pharmacology

Contact Info

Product

Resources

About