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1.
Sci Adv ; 8(18): eabm4131, 2022 May 06.
Article in English | MEDLINE | ID: mdl-35507667

ABSTRACT

Understanding variability in the size and location of large earthquakes along subduction margins is crucial for evaluating seismic and tsunami hazards. We present a coseismic slip model for the 2021 M8.2 Chignik earthquake and investigate the relationship of this earthquake to previous major events in the Alaska Peninsula region and to interseismic coupling. Stress changes from the 2020 M7.8 Simeonof event triggered the Chignik event, and together, the earthquakes partially filled an unruptured section along a 3000-km subduction margin that has experienced a series of ruptures along almost its entire length over the past century. Variations in coupling and structural characteristics may make the region more prone to nucleating M7 to M8 events rather than larger M > 8.5 earthquakes. Stress changes and rupture areas suggest that the two recent earthquakes may be part of an 80-year-long rupture cascade and may have advanced seismic hazard in the region.

2.
J Nutr ; 148(8): 1209-1216, 2018 08 01.
Article in English | MEDLINE | ID: mdl-30137478

ABSTRACT

Background: Zearalenone (ZEN) can cause serious defects in development and reproduction in humans and animals. Silymarin shows antioxidant and estrogenic effects. Objective: This study was conducted to determine if silymarin can antagonize ZEN-induced hepatic and reproductive toxicities. Methods: Thirty-five 21-d-old female Sprague-Dawley rats (n = 7/diet) were fed a control diet (Ctrl) or Ctrl plus 20 mg ZEN/kg or Ctrl plus 20 mg ZEN/kg with 100, 200, or 500 mg silymarin/kg for 6 wk. Serum, livers, ovaries, and uterus were collected at week 6 for biochemistry, hormone, and redox status and selected gene and protein assays. Results: The consumption of ZEN decreased (P < 0.05) the final body weight by 17.9%, induced liver injury, increased (P < 0.05) aspartate aminotransferase and alkaline phosphatase activities, and decreased (P < 0.05) total protein and albumin concentrations in serum by 16.7-40.6%. ZEN also caused reproductive toxicity, including decreased (P < 0.05) 17ß-estradiol and increased (P < 0.05) follicle-stimulating hormone concentrations in serum by 12.7-46.3% and induced histopathologic alterations in the liver, ovaries, and uterus. Interestingly, these alterations induced by ZEN were alleviated (P < 0.05) by silymarin supplementation at 100, 200, and 500 mg/kg. Moreover, silymarin supplementation at the 3 doses mitigated (P < 0.05) ZEN-induced impairment in hepatic glutathione peroxidase activity, total antioxidant capacity, and malondialdehyde concentration by 17.6-100%. Meanwhile, silymarin supplementation at all doses upregulated (P < 0.05) phospho-ribosomal protein S6 kinase 1 (p-RPS6KB1) and 3ß-hydroxysteroid dehydrogenase (HSD3B) by 43.0-121% but downregulated (P < 0.05) AMP-activated protein kinase (AMPK) and 3α-hydroxysteroid dehydrogenase (HSD3A) in the liver relative to the ZEN group by 11.2-40.6%. In addition, silymarin supplementation at all doses elevated (P < 0.05) HSD3B by 1.8- to 2.5-fold and decreased (P < 0.05) estrogen receptor 1 (ESR1), ATP binding cassette (ABC) c1, and Abcc5 in ovaries and the uterus by 10.7-63.2%. Conclusion: Dietary silymarin supplementation at 100, 200, and 500 mg/kg protected rats from ZEN-induced hepatotoxicity and reproductive toxicity, potentially through improvement in the antioxidant capacity and regulation in the genes related to protein synthesis, ZEN metabolism, hormone synthesis, and ABC transporters in the tissues.


Subject(s)
Antioxidants/therapeutic use , Chemical and Drug Induced Liver Injury/prevention & control , Liver/drug effects , Reproduction/drug effects , Silybum marianum/chemistry , Silymarin/therapeutic use , Zearalenone/toxicity , AMP-Activated Protein Kinases/metabolism , ATP-Binding Cassette Transporters/metabolism , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Blood Proteins/metabolism , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Dietary Supplements , Estrogen Receptor alpha/blood , Female , Glutathione Peroxidase/metabolism , Hormones/blood , Hydroxysteroid Dehydrogenases/metabolism , Liver/enzymology , Liver/pathology , Malondialdehyde/blood , Multidrug Resistance-Associated Proteins/metabolism , Ovary/drug effects , Ovary/pathology , Phytotherapy , Rats, Sprague-Dawley , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , Silymarin/pharmacology , Uterus/drug effects , Uterus/pathology
3.
Food Chem Toxicol ; 116(Pt B): 11-19, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29627501

ABSTRACT

The present study investigated the reproductive and developmental toxicity of male offspring induced by prenatal ZEN exposure and explored the possible mechanism. 64 pregnant rats were allocated into four groups and fed with ZEN contaminated (0, 5, 10 and 20 mg/kg) diet during the whole gestation period. The results showed that, F1 male foetal viability was not affected while newborn bodyweight (BW) was significantly decreased after prenatal exposure to ZEN. Decreased BW was found on postnatal day (PND) 21 but not on PND 63 in ZEN exposed male rats. Moreover, adult testis weight increased with seminiferous tubules atrophy as well as decreased spermatocytes and mature sperms (35% and 31%) in ZEN-treated rats. Meanwhile, circulating levels of luteinizing hormone and testosterone decreased while estradiol increased in ZEN-treated rats. These impairments concurred with down-regulations of 3ß-HSD and StAR in both mRNA and protein levels in weaned and adult testis. Furthermore, gene and protein expressions of GnRHr and Esr1 were inhibited in the ZEN-treated foetal brain. These results suggested that prenatal ZEN exposure disrupted the system regulating the reproductive hormones and testis development through hormone related genes, which may result in a reproductive dysfunction in adult male offspring.


Subject(s)
3-Hydroxysteroid Dehydrogenases/genetics , Brain/drug effects , Estradiol/blood , Estrogen Receptor alpha/genetics , Estrogens, Non-Steroidal/toxicity , Luteinizing Hormone/blood , Maternal Exposure , Phosphoproteins/genetics , Prenatal Exposure Delayed Effects , Receptors, LHRH/genetics , Reproduction/drug effects , Testis/drug effects , Testosterone/blood , Zearalenone/toxicity , ATP-Binding Cassette Transporters/genetics , Animals , Brain/metabolism , Dose-Response Relationship, Drug , Female , Gene Expression , Male , Organ Size/drug effects , Pregnancy , Rats, Sprague-Dawley , Testis/growth & development , Testis/pathology
4.
Toxins (Basel) ; 9(1)2017 01 05.
Article in English | MEDLINE | ID: mdl-28067781

ABSTRACT

Zearalenone (ZEN) is an oestrogenic mycotoxin commonly found in food and feed products and can affect reproduction and development in both humans and animals. This study aimed to determine the toxic effects of ZEN on maternal SD rats and the F1 female offspring. Sixty-four pregnant rats were divided into 4 groups and exposed to feed contaminated with ZEN (0, 5, 10, and 20 mg/kg feed) on gestational days (GDs) 0-21. Compared with the controls, the groups exposed to 10 and 20 mg/kg ZEN showed significantly decreased feed intake and body weight of pregnant rats and/or female offspring. Meanwhile, 20 mg/kg ZEN significantly decreased the birth weight and viability of F1 newborn rats. Moreover, 10 and 20 mg/kg ZEN diets increased follicle-stimulating hormone concentrations but decreased oestradiol in both maternal and F1 adult rats. In the F1 generation, ZEN caused no pathological changes in ovaries and uterus in weaned rats, but significant follicular atresia and a thinning uterine layer were found in F1 female adult rats in the 20 mg/kg ZEN group. These impairments concurred with the inhibited mRNA and protein levels of oestrogen receptor-alpha (Esr1) and 3ß-hydroxysteroid dehydrogenase (HSD) in the adult uterus and/or ovaries. Furthermore, 10 and/or 20 mg/kg ZEN exposure significantly reduced Esr1, gonadotropin-releasing hormone receptor (GnRHr), and ATP binding cassette transporters b1 and c1 (ABCb1 and ABCc1) in the placenta and foetal and weaned F1 brains, and also produced a dose-dependent increase in 3ß-HSD in the placenta. Additionally, 20 mg/kg ZEN significantly upregulated ABCc5 expression in the placenta and ovaries of weaned rats. These results suggested that prenatal ZEN exposure in rats affected maternal and foetal development and may lead to long-term reproductive impairment in F1 adult females.


Subject(s)
Maternal Exposure/adverse effects , Prenatal Exposure Delayed Effects , Reproduction/drug effects , Zearalenone/toxicity , Age Factors , Animal Feed , Animals , Birth Weight/drug effects , Dose-Response Relationship, Drug , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Food Microbiology , Gene Expression Regulation, Developmental , Gestational Age , Ovary/drug effects , Ovary/metabolism , Ovary/pathology , Pregnancy , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats, Sprague-Dawley , Risk Assessment , Uterus/drug effects , Uterus/metabolism , Uterus/pathology , Zearalenone/administration & dosage
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