2018: ER apoptosis in thyroid injury caused by F- in rat

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2018: ER apoptosis in thyroid injury caused by F- in rat

Postby admin » Thu May 02, 2019 6:31 am

Yu LY, Cui YS, Liu HL - "Effects of endoplasmic reticulum stress-induced
apoptosis in thyroid injury caused by fluoride in rat" Zhonghua Yu Fang Yi Xue
Za Zhi. 2018 Nov 6;52(11):1182-1187. doi:
10.3760/cma.j.issn.0253-9624.2018.11.017. Chinese. PubMed PMID: 30419706.

Objective: To explore the effects of endoplasmic reticulum stress-induced
apoptosis in thyroid injury of rats caused by excessive fluoride intake.

Methods:
All 40 Wistar rats were randomly divided into four groups, control group, low
fluoride group, medium fluoride group and high fluoride group. The rats in
control group were fed with tap water (fluoride concentration=0.344 mg/L) and the
experimental rats were fed with the water contaminated fluoride with the dose of
5, 10 and 20 mg/L. 10 rats (female: male=1∶1) in each group were sacrificed after
8 months of exposure through drinking water. The contents of urine fluoride were
detected by fluorine ion selective electrode method. Morphology of thyroid was
observed through light microscope and apoptosis in thyroid were detected by the
terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)
assay. The mRNA and protein expressions of glucose-regulated protein 78 (GRP78)
and C/EBP homologous protein (CHOP) were analyzed by RT-PCR and
immunohistochemistry respectively, and results were compared among groups.

Results: The contents of urine fluoride in all fluoride treated groups were
separately (4.74±1.88), (7.70±2.82) and (10.50±2.92) mg/L, which were gradually
higher than that of control group (2.23±0.54) mg/L (P<0.05). Morphological
changes were found in thyroid tissues of fluoride treated groups, thyroid
follicular hyperplasia or even no cavity cell clusters were observed. Apoptosis
in thyroid were notably increased in fluoride treated groups. The mRNA expression
levels of GRP78 in all fluoride treated groups were separately 1.30±0.42,
1.39±0.29 and 1.50±0.27, which were significantly higher than that of control
group (0.93±0.24) (P<0.05). And the mRNA expression levels of CHOP in medium and
high fluoride groups were separately 1.17±0.29 and 1.30±0.26, which were
significantly higher than that of control group (0.91±0.20) (P<0.05). The protein
expression levels of GRP78 and CHOP in medium and high fluoride groups were
respectively 29.68±4.04, 29.90±3.74 and 4.05±1.62, 4.44±1.81, which were
significantly higher than those in the control group (separately 23.80±6.36,
2.27±0.89) (P<0.05).

Conclusion: Excessive-fluoride intake can induce thyroid
injury, and endoplasmic reticulum stress-induced apoptosis might be involved in
the injury.

Publisher: 目的: 探讨内质网应激诱导的细胞凋亡在过量氟导致的大鼠甲状腺损伤中的作用。 方法:
将40只Wistar大鼠采用随机数字表法分成4组,分别为对照组和低、中、高浓度氟化钠(NaF)染毒组。对照组大鼠饮用自来水,氟离子浓度为0.344
mg/L,低、中、高浓度NaF染毒组饮用含NaF浓度分别为5、10、20
mg/L的自来水,染毒8个月后每组处死雌雄大鼠各5只。选择电极法检测尿氟浓度情况,光镜下观察甲状腺组织形态,脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNE
L)检测甲状腺组织凋亡细胞,RT-PCR和免疫组化法检测甲状腺组织中葡萄糖调节蛋白78(GRP78)和C/EBP同源蛋白(CHOP)的mRNA和蛋白的表达,比较各
组间指标差异。 结果:
与对照组[(2.23±0.54)mg/L]比较,低、中、高浓度NaF染毒组尿氟浓度分别为(4.74±1.88)、(7.70±2.82)、(10.50±2.92)m
g/L(P<0.05)。NaF染毒组大鼠甲状腺组织形态发生了明显的变化,可见较多增生小滤泡,甚至无腔细胞团。TUNEL检测发现染毒组大鼠甲状腺凋亡细胞数明显增加,
低、中、高浓度NaF染毒组GRP78
mRNA表达水平(分别为1.30±0.42、1.39±0.29、1.50±0.27)高于对照组(0.93±0.24),P<0.05;中、高浓度NaF染毒组CHOP
mRNA表达水平(分别为1.17±0.29、1.30±0.26)亦高于对照组(0.91±0.20),P<0.05。中、高浓度NaF染毒组大鼠甲状腺组织中GPR78
蛋白(分别为29.68±4.04、29.90±3.74)和CHOP蛋白的表达水平(分别为4.05±1.62、4.44±1.81)均高于对照组(23.80±6.36
、2.27±0.89), P<0.05。 结论: 过量氟可造成甲状腺损伤,可能与内质网应激诱导的细胞凋亡有关。.
DOI: 10.3760/cma.j.issn.0253-9624.2018.11.017
PMID: 30419706 [Indexed for MEDLINE]

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