The Environmental Pollutant Tributyltin Chloride Disrupts the Hypothalamic-Pituitary-Adrenal Axis at Different Levels in Female Rats

Merlo, Eduardo; Podratz, Priscila L.; Sena, Gabriela C.; Araújo, Julia F.P. de; Freitas-Lima, Leandro Ceotto; Alves, Izabela Silva Sinara; Gama-de-Souza, Letícia Nogueira da; Pelição, Renan; Rodrigues, L. C. M.; Brandão, Poliane A.A.; Carneiro, Maria Tereza Weitzel Dias; Pires, Rita Gomes Wanderley; Martins-Silva, Cristina; Alarcon, T. A.; Miranda-Alves, Leandro; Silva, Ian V.; Graceli, Jones Bernardes

doi:10.1210/en.2015-1896

Cited by 50 publications

(41 citation statements)

References 126 publications

(117 reference statements)

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“…Although we have not measured the activity of NQO1 and 2 enzymes, one may expect the VK3 isoform to exert more powerful effects on osteocalcin y-carboxylation. In addition, VK1 have less affinity to LDL and VLDL [18,19]. Actually, our data indicated that high y-carboxylated isoforms of osteocalcin are present into serum of animals treated with VK3.…”

Section: Discussionmentioning

confidence: 63%

“…However, post-menopausal women are mostly affected by osteoporosis than any other people indicating that female gonadal hormones, particularly estrogen, are crucial for the pathogenesis of this illness [18]. Several studies have shown that their bone loss is mainly caused by increased bone resorption rate over bone formation [4,19]. Recently, the role of vitamin K deficiency has been associated to osteoporosis and bone breakings.…”

Section: Discussionmentioning

confidence: 99%

“…Results were expressed in fold of amplification. Better description of methodology were scrutinized in the following references [18,19].…”

Section: Bone Expression Mrna Calbindin 28 Kda (Cbp28k)mentioning

confidence: 99%

“…As long as the effects of VK in bone metabolisms are still inconclusive, we decided to investigate its effects in a well-established model for osteoporosis, the ovariectomized (OVX) mice [17][18][19]. Surgical removal of the ovaries mimics menopause resulting in a suitable model to investigate mechanisms of VK action in bone as well as its interaction with estrogen either on BMD or microarchitecture [19].…”

Section: Introductionmentioning

confidence: 99%

“…Surgical removal of the ovaries mimics menopause resulting in a suitable model to investigate mechanisms of VK action in bone as well as its interaction with estrogen either on BMD or microarchitecture [19]. Moreover, we analyzed several parameters of mineral homeostasis in animals subjected to long term treatment of pharmacological doses of VK with normal ovary function (SHAM operated) and OVX.…”

Section: Introductionmentioning

confidence: 99%

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Vitamin K Supplementation Modulates Bone Metabolism and Ultra-Structure of Ovariectomized Mice

Rangel¹,

Siqueira²,

Soares³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Osteoporosis is a bone metabolic disease that affects mostly post-menopausal women. There has been shown that vitamin K (VK) supplementation during menopause may decrease bone loss as well as risk of bone breaking. Aiming to clarify the beneficial role of VK in bone metabolism during menopause, we investigated mineral metabolism and bone ultrastructure of ovariectomized (OVX) mice. Methods: To determine the effects chronic use of VK in bone structure and mineral metabolism in OVX mice, we used several methods, such as DXA, µCTScan, and SEM as well as biomolecular techniques, such as ELISA and qRT-PCR. In addition, complete analysis of serum hormonal and other molecules associated to bone and lipid metabolism were evaluated overview the effects of VK in menopause murine model. Results: VK treatment significantly affects Pi metabolism independently of OVX, changing Pi plasma, urinary output, balance, and Pi bone mass. Interestingly, VK also increased VLDL in mice independently of castration. In addition, VK increased compact bone mass in OVX mice when we evaluated it by DXA, histomorphometry, µCTScanning. VK increased bone formation markers, osteocalcin, HYP- osteocalcin, and AP whereas it decreased bone resorption markers, such as urinary DPD/creatinine ratio and plasmatic TRAP. Surprisingly, SEM images revealed that VK treatment led to amelioration of microfractures observed in OVX untreated controls. In addition, SHAM operated VK treated mice exhibited higher number of migrating osteoblasts and in situ secretion of AP. OVX led to decreased to in situ secretion of AP that was restored by VK treatment. Moreover, VK treatment increased mRNA expression of bone Calbindin 28KDa independently of OVX. Conclusion: VK treatment in OVX mice exhibited beneficial effects on bone ultrastructure, mostly by altering osteoblastic function and secretion of organic bone matrix. Therefore, VK could be useful to treat osteopenic/osteoporotic patients.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

“…Results were expressed in fold of amplification. Better description of methodology were scrutinized in the following references [18,19].…”

Section: Bone Expression Mrna Calbindin 28 Kda (Cbp28k)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Vitamin K Supplementation Modulates Bone Metabolism and Ultra-Structure of Ovariectomized Mice

Rangel¹,

Siqueira²,

Soares³

et al. 2018

Cell Physiol Biochem

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Germanium, Tin, and Copper

King,

Avery

2023

Patty's Toxicology

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A German chemist Clemens A. Winkler first isolated Germanium in 1886 from the mineral argyrodite. Germanium (Ge) is a semiconducting metal from Group IVA of the periodic table, and it forms a series of hydrides. Interest in the organogermanium compounds has centered on their antimicrobial activity and the fact that their mammalian toxicity is lower than the corresponding derivatives of tin or lead. Today, germanium is used in the computer industry (as resistors on computer chips), in fiber optics, solar applications, and metallurgy, and has also been used in supplements and for chemotherapy agents. The inorganic compound, Ge tetrachloride, has been shown to cause skin and eye irritation, and inhalation of high exposure concentrations can cause necrosis of the tracheal mucosa, bronchitis, and interstitial pneumonitis. In recent years, germanium nanoparticles (NPs) have received increased attention as a favorable alternative to II–VI and IV–VI semiconductor materials. It was found that GE nano length imogolites persisted in the lungs of tested animals and promoted genotoxicity, sustained inflammation, and fibrosis. The Bronze Age began approximately 3500 BCE with the discovery that alloying tin (Sn) with easily smelted soft copper made it harder and stronger. Tin and copper are important for the manufacture of numerous commercially valuable products including electrical conductors, piping, and antimicrobial agents. Tin is a solid, unreactive metal in Group IVA of the periodic table and has the largest number of stable isotopes of any element. Tin also has many unstable isotopes with half‐lives ranging from 2.2 min to 105 years. The physical and chemical properties of tin and some of its compounds are provided. Organotins, such as tributyltin (TBT) and trimethyltin (TMT) compounds, have drawn much attention because of their toxicity and wide range of adverse effects in experimental animals and in humans. Laboratory research has demonstrated that tributyltin is an endocrine disruptor in mammals, affects the immune system, is reported to be teratogenic, and is a reproductive and developmental toxicant. Occupational exposure to trimethyltin has been shown to increase the risk of kidney stones among TMT‐exposed workers. Copper (Cu) is in Group IB of the periodic table. The electrical conductivity and malleability of copper are important commercial properties of the metal. Exposure to copper can occur from environmental sources such as food, water from copper pipes, and soil ingestion near copper smelting operations. The adverse health effects associated with copper production may be due to the sulfur oxides generated during smelting or because of the impurities, such as arsenic and antimony. Results from numerous experimental studies support the position that reactive oxygen species (ROS)‐generated oxidative damage plays an important role in Cu toxicity. Copper processing workers were found to have had significantly lower pulmonary function parameter test results, significantly increased serum levels of malondialdehyde, and their total antioxidative capacity and glutathione concentrations were significantly lower than controls. Also, based on the comet assay, it was found that significant DNA damage occurred in leukocytes among the copper processing workers. Copper nanoparticles are being used in a wide range of applications. Experimental studies in animals have reported that inhalation of Cu NPs was shown to cause the increased deposition of copper in the lung and liver and an undesired modulation of immune system response. Inhalation of Cu NPs in rats resulted in dose‐dependent lung inflammation and cytotoxicity, and histopathology examinations of the lungs revealed alveolitis, bronchitis, and vacuolation of the respiratory epithelium and emphysema. In a study of the hemolytic effects of copper oxide (CuO) nanoparticles and bulk CuO in human red blood cells, it was demonstrated that CuO NPs caused toxic hemolytic effects in a concentration‐dependent manner and that the CuO NPs effectively destroy human red blood cells in comparison to bulk CuO.

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The ameliorative effect of Moringa oleifera oil on tributyltin‐induced brain toxicity in albino rats

Sakr

Rashad

Abaza

2021

Environmental Toxicology

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Tributyltin (TBT) is an organotin compound widely used as a biocide in antifouling paints. Moringa oleifera oil (MOO) has a promising antioxidant potential, which necessitates further exploration. This study was conducted to investigate the potential protective effect of MOO against TBT‐induced brain toxicity. The 30 rats were grouped into five groups (six each), Group I negative control, Group II positive control (vehicle), Group III MOO (5 ml/kg body weight [b.wt.]), Group IV TBT (10 mg/kg b.wt.), and Group V TBT & MOO. All treatments were given orally for 28 days. Thereafter, brains were exposed to oxidative stress and neurological parameters analyses. Histopathological and immunohistochemical (caspase‐3, Bax, Bcl‐2) examinations were also carried out. In rats administered TBT, increased malondialdehyde level, decreased reduced glutathione, and low total antioxidant capacity levels were in support of oxidative stress mechanism. Neurotoxicity was indicated by high nitric oxide level and increased acetylcholinestrase activity. Along with the histopathological alterations, the dysregulated expression of caspase‐3, Bax, and Bcl‐2 were indicative of the apoptotic mechanism mediated by TBT. Co‐administration of MOO with TBT ameliorated the aforementioned toxic effects. In conclusion, TBT causes brain toxicity via oxidative, nitrosative, and apoptotic mechanisms. MOO demonstrates protective effect against TBT‐induced brain toxicity mostly via potent antioxidant and antiapoptotic properties.

show abstract

The Environmental Pollutant Tributyltin Chloride Disrupts the Hypothalamic-Pituitary-Adrenal Axis at Different Levels in Female Rats

Cited by 50 publications

References 126 publications

Vitamin K Supplementation Modulates Bone Metabolism and Ultra-Structure of Ovariectomized Mice

Vitamin K Supplementation Modulates Bone Metabolism and Ultra-Structure of Ovariectomized Mice

Germanium, Tin, and Copper

The ameliorative effect of Moringa oleifera oil on tributyltin‐induced brain toxicity in albino rats

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