Long-term melatonin treatment reduces ovarian mass and enhances tissue antioxidant defenses during ovulation in the rat

Chuffa, Luiz Gustavo de Almeida; Amorim, João Paulo de Arruda; Teixeira, Giovana Rampazzo; Mendes, Leonardo O.; Fioruci, Beatriz Aparecida; Pinheiro, Patrícia Fernanda Felipe; Seiva, Fábio Rodrigues Ferreira; Novelli, Ethel L. B.; Júnior, W. Mello; Martinez, Marcelo; Martinez, Francisco Eduardo

doi:10.1590/s0100-879x2011007500018

Cited by 34 publications

(33 citation statements)

References 40 publications

(40 reference statements)

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“…On the other hand, the lack of a significant increase of sperm lipid peroxidation at 32 days pi suggests that a fraction of the germ cells of the seminiferous epithelium is possibly eliminated by apoptosis. The results of this study support the importance of melatonin as a protective agent on the biological processes in vivo, especially in reproductive and seminal patterns (Reiter et al, 2009;Chuffa et al, 2011).…”

Section: Sarabia L; Espinoza-navarro O; Maurer I; Ponce C and Bsupporting

confidence: 79%

Protective Effect of Melatonin on Damage in the Sperm Parameters of Mice Exposed to Diazinon

et al. 2011

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SUMMARY:Since normal sperm parameters can be altered by organophosphorous pesticides, this study intended to determine if melatonin is able to prevent the damage on sperm quality after an acute exposure to diazinon. Adult male mice were injected intraperitoneally with melatonin, diazinon (1/3 or 2/3 LD50) or both, and sperm parameters were evaluated on days 1 or 32 post injection. Groups treated with diazinon showed elevated lipid peroxidation levels on day 1 post treatment, while groups pretreated with melatonin before diazinon showed no difference compared to control. Sperm count showed a significant decrease in both diazinontreated groups only on day 32 post injection; no differences were observed in groups pretreated with melatonin prior to diazinon compared to control. The percentage of abnormal sperm morphology increased in the diazinon-treated groups only on day 32 postinjection. The administration of melatonin prior to exposure to diazinon prevents the alteration of sperm parameters commonly caused by organophosphates, possibly due to its antioxidant properties.

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Section: Sarabia L; Espinoza-navarro O; Maurer I; Ponce C and Bsupporting

confidence: 79%

Protective Effect of Melatonin on Damage in the Sperm Parameters of Mice Exposed to Diazinon

et al. 2011

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“…The relationship between oxidative stress and the antioxidative properties of Mel have been well documented 21,36, and high production of reactive oxygen species (ROS) is strongly associated to cell damage and cancer. Notably, Mel treatment has prevented many of the H 2 O 2 -induced alterations in the MAPK and mTOR signaling pathways in H4IIE hepatoma cells 18.…”

Section: Discussionmentioning

confidence: 99%

“…dissolved in 0.04 mL of 95% EtOH and then diluted in 0.3 mL of 0.9% NaCl (vehicle) at a steady-state concentration of 0.3 mg/mL. The daily injections were administered nocturnally (between 18:30 - 19:00 h) over the period of 60 consecutive days 21.…”

Section: Methodsmentioning

confidence: 99%

Melatonin Attenuates Her-2, p38 MAPK, p-AKT, and mTOR Levels in Ovarian Carcinoma of Ethanol-Preferring Rats

Ferreira¹,

Martinez²,

Camargo³

et al. 2014

J. Cancer

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Epidermal growth factor receptors 2 (Her-2) and 4 (Her-4) are closely associated with ovarian cancer (OC) progression and metastasis, and a more complete understanding of these signaling pathways allow the development of new therapeutic strategies. Melatonin (Mel) is recognized as having several anticancer properties and has been reported to modulate Her-2 system in aggressive tumors. Here, we investigated OC and the role of Mel therapy on the Her-2- and Her-4-signaling pathway related to downstream molecules in an ethanol-preferring rat model. To induce OC, the left ovary was injected directly with a single dose of 100 µg 7,12-dimethylbenz(a)anthracene (DMBA) dissolved in 10 µL of sesame oil under the bursa. Right ovaries were used as sham-surgery controls. After developing OC, half of the animals received i.p. injections of Mel (200 µg/100 g b.w./day) for 60 days. While Mel therapy was unable to reduce Her-4 and phosphoinositide 3-kinase (PI3K) levels, it was able to suppress the OC-related increase in the levels of the Her-2, p38 mitogen-activated protein kinases (p38 MAPK), protein kinase B (phospho-AKT), and mammalian target of rapamycin (mTOR). In addition, Mel significantly attenuated the expression of Her-2, p38 MAPK, and p-AKT, which are involved in OC signaling during ethanol intake. Collectively, our results suggest that Mel attenuates the Her-2-signaling pathway in OC of ethanol-preferring rats, providing an effective contribution for further development of adjuvant therapies.

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“…doses of 200 mg/100 g BW dissolved in 0.04 ml of 95% EtOH and then diluted in 0.3 ml of 0.9% NaCl (vehicle) at a final concentration of 0.3 mg/ml. The daily injections were administered at night (between 1830 and 1900 h) for 60 consecutive days (Chuffa et al 2011b). This protocol relies on previous works in which long-term Mel therapy was able to reduce tumor size and tumor cell survival.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

Apoptosis is triggered by melatonin in an in vivo model of ovarian carcinoma

Chuffa¹,

Alves²,

Martinez³

et al. 2015

Endocrine-Related Cancer

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Apoptosis plays an important role in the treatment of cancer, and targeting apoptosis-related molecules in ovarian cancer (OC) is of great therapeutic value. Melatonin (Mel) is an indoleamine displaying several anti-cancer properties and has been reported to modulate apoptosis signaling in multiple tumor subtypes. We investigated OC and the role of Mel therapy on the pro-apoptotic (p53, BAX, caspase-3, and cleaved caspase-3) and anti-apoptotic (Bcl-2 and survivin) proteins in an ethanol (EtOH)-preferring rat model. To induce OC, the left ovary was injected directly with a single dose of 100 mg 7,12-dimethylbenz(a)anthracene dissolved in 10 ml of sesame oil under the bursa. Right ovaries were used as sham-surgery controls. After developing OC, half of the animals received i.p. injections of Mel (200 mg/100 g BW per day) for 60 days. Body weight gain, EtOH consumption, and energy intake were unaffected by the treatments. Interestingly, absolute and relative OC masses showed a significant reduction after Mel therapy, regardless of EtOH consumption. To accomplish OC-related apoptosis, we first observed that p53, BAX, caspase-3, and cleaved caspase-3 were downregulated in OC tissue while Bcl-2 and survivin were overexpressed. Notably, Mel therapy and EtOH intake promoted apoptosis along with the upregulation of p53, BAX, and cleaved caspase-3. Fragmentation of DNA observed by TUNEL-positive nuclei was also enhanced following Mel treatment. In addition, Bcl-2 was downregulated by the EtOH intake and lower survivin levels were observed after Mel therapy. Taken together, these results suggest that Mel induce apoptosis in OC cells of EtOH-preferring animals.Key Words " ovarian cancer " melatonin " pro-apoptotic protein " anti-apoptotic protein

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Long-term melatonin treatment reduces ovarian mass and enhances tissue antioxidant defenses during ovulation in the rat

Cited by 34 publications

References 40 publications

Protective Effect of Melatonin on Damage in the Sperm Parameters of Mice Exposed to Diazinon

Protective Effect of Melatonin on Damage in the Sperm Parameters of Mice Exposed to Diazinon

Melatonin Attenuates Her-2, p38 MAPK, p-AKT, and mTOR Levels in Ovarian Carcinoma of Ethanol-Preferring Rats

Apoptosis is triggered by melatonin in an in vivo model of ovarian carcinoma

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