The role of 17β-estradiol metabolites in chromium-induced oxidative stress

Oncological diseases, due to the still increasing morbidity and mortality, are one of the main problems of modern medicine. Cancer of the mammary gland is the most common cancer among women around the world, and is the second cause of cancer deaths in this group, immediately after lung cancer. This kind of cancer belongs to an estrogen-dependent cancer, with proven associations with hormonal disorders in the body, occurring especially in the perimenopausal period and among women using hormone replacement therapy, as well as a result of the action of various xenobiotics that may interact with the estrogen receptor. Hormone steroids are widely used in medicine and their side effects are constantly discussed. The role of these compounds and their metabolites in maintaining hormonal balance is well understood, while many studies indicate the possible contribution of these steroids in the progression of the cancer process, especially in mammary gland tissue. Therefore, the genotoxic action of this group of compounds is still studied. Due to the limited number of scientific reports, the aim of this paper was to review and critically analyze data from the literature regarding the participation of estrogens (17β-estradiol) and their metabolites (2-methoxy estradiol, 4-hydroxy estradiol, 16α-hydroxyestrone) in the induction of carcinogenesis in mammary gland, in particular concerning the genotoxic activity of 17β-estradiol metabolites.

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17β-estradiol improves hepatic mitochondrial biogenesis and function through PGC1B

Journal of Endocrinology ◽

10.1530/joe-16-0350 ◽

2017 ◽

Vol 232 (2) ◽

pp. 297-308 ◽

Cited By ~ 14

Author(s):

Bel M Galmés-Pascual ◽

Antonia Nadal-Casellas ◽

Marco Bauza-Thorbrügge ◽

Miquel Sbert-Roig ◽

Francisco J García-Palmer ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Biogenesis ◽

Oxidative Capacity ◽

Protective Role ◽

Rat Tissues ◽

Peroxisome Proliferator ◽

Ovx Rats ◽

17Β Estradiol ◽

And Function

Sexual dimorphism in mitochondrial biogenesis and function has been described in many rat tissues, with females showing larger and more functional mitochondria. The family of the peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) plays a central role in the regulatory network governing mitochondrial biogenesis and function, but little is known about the different contribution of hepatic PGC1A and PGC1B in these processes. The aim of this study was to elucidate the role of 17β-estradiol (E2) in mitochondrial biogenesis and function in liver and assess the contribution of both hepatic PGC1A and PGC1B as mediators of these effects. In ovariectomized (OVX) rats (half of which were treated with E2) estrogen deficiency led to impaired mitochondrial biogenesis and function, increased oxidative stress, and defective lipid metabolism, but was counteracted by E2 treatment. In HepG2 hepatocytes, the role of E2 in enhancing mitochondrial biogenesis and function was confirmed. These effects were unaffected by the knockdown of PGC1A, but were impaired when PGC1B expression was knocked down by specific siRNA. Our results reveal a widespread protective role of E2 in hepatocytes, which is explained by enhanced mitochondrial content and oxidative capacity, lower hepatic lipid accumulation, and a reduction of oxidative stress. We also suggest a novel hepatic protective role of PGC1B as a modulator of E2 effects on mitochondrial biogenesis and function supporting activation of PGC1B as a therapeutic target for hepatic mitochondrial disorders.

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Oxidative stress parameters induced by exposure to either cadmium or 17β-estradiol on Mytilus galloprovincialis hemocytes. The role of signaling molecules

Aquatic Toxicology ◽

10.1016/j.aquatox.2013.11.005 ◽

2014 ◽

Vol 146 ◽

pp. 186-195 ◽

Cited By ~ 37

Author(s):

Sophia Koutsogiannaki ◽

Silvia Franzellitti ◽

Elena Fabbri ◽

Martha Kaloyianni

Keyword(s):

Oxidative Stress ◽

Mytilus Galloprovincialis ◽

Signaling Molecules ◽

Oxidative Stress Parameters ◽

17Β Estradiol ◽

Stress Parameters

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17-β Estradiol Rescued Immature Rat Brain against Glutamate-Induced Oxidative Stress and Neurodegeneration via Regulating Nrf2/HO-1 and MAP-Kinase Signaling Pathway

Antioxidants ◽

10.3390/antiox10060892 ◽

2021 ◽

Vol 10 (6) ◽

pp. 892

Author(s):

Ibrahim Khan ◽

Kamran Saeed ◽

Min Gi Jo ◽

Myeong Ok Kim

Keyword(s):

Oxidative Stress ◽

Map Kinase ◽

Rat Brain ◽

Biological Activities ◽

Glutamate Excitotoxicity ◽

Glutamate Signaling ◽

Synaptic Markers ◽

17Β Estradiol ◽

Brain Oxidative Stress

Dysregulated glutamate signaling, leading to neuronal excitotoxicity and death, has been associated with neurodegenerative pathologies. 17β-estradiol (E2) is a human steroid hormone having a role in reproduction, sexual maturation, brain health and biological activities. The study aimed to explain the neuroprotective role of E2 against glutamate-induced ROS production, MAP kinase-dependent neuroinflammation, synaptic dysfunction and neurodegeneration in the cortex and hippocampus of postnatal day 7 rat brain. Biochemical and immunofluorescence analyses were applied. Our results showed that a single subcutaneous injection of glutamate (10 mg/kg) induced brain oxidative stress after 4 h by disturbing the homeostasis of glutathione (GSH) and revealed an upsurge in ROS and LPO levels and downregulated the expression of Nrf2 and HO-1 antioxidant protein. The glutamate-exposed P7 pups illustrated increased phosphorylation of stress-activated c-Jun N-terminal kinase (JNK) and p38 kinase (p38) and downregulated expression of P-Erk1/2. This was accompanied by pathological neuroinflammation as revealed by enhanced gliosis with upregulated expression of GFAP and Iba-1, and the activation of proinflammatory cytokines (TNF-α) in glutamate-injected P7 pups. Moreover, exogenous glutamate also reduced the expression of synaptic markers (PSD-95, SYP) and induced apoptotic neurodegeneration in the cortical and hippocampal regions by dysregulating the expression of Bax, Bcl-2 and caspase-3 in the developing rat brain. On the contrary, co-treatment of E2 (10 mg/kg) with glutamate significantly abrogated brain neuroinflammation, neurodegeneration and synapse loss by alleviating brain oxidative stress by upregulating the Nrf2/HO-1 antioxidant pathway and by deactivating pro-apoptotic P-JNK/P-p38 and activation of pro-survival P-Erk1/2 MAP kinase pathways. In brief, the data demonstrate the neuroprotective role of E2 against glutamate excitotoxicity-induced neurodegeneration. The study also encourages future studies investigating if E2 may be a potent neuroprotective and neurotherapeutic agent in different neurodegenerative diseases.

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