PMID- 33387433
OWN - NLM
STAT- MEDLINE
DCOM- 20210105
LR  - 20210105
IS  - 1426-9686 (Print)
IS  - 1426-9686 (Linking)
VI  - 48
IP  - 288
DP  - 2020 Dec 22
TI  - Implementation of programmed cell death in circulating neutrophils and its 
      special characteristics in experimentally induced hyperhomocysteinemia in a 
      setting of thyroid dysfunction.
PG  - 437-442
AB  - Cardiovascular (CV) disease continues to be the main cause of morbidity and 
      mortality in worldwide. Hyperhomocysteinemia (HHCy) is a novel metabolic risk 
      factor of vascular damage. In addition to that, there is evidence that HHCy 
      management with folic acid and vitamin B supplements prevents atherosclerosis and 
      its sequelae. Oxidative stress is one of the mechanisms behind the cardiotoxic 
      effects of high homocysteine levels. On the one hand, HHCy facilitates 
      endothelial dysfunction, probably as a result of impaired synthesis and/or 
      inactivation of nitrogen (II) oxide (NO). On the other hand, oxidation of 
      homocysteine is accompanied by formation of reactive oxygen species (ROS), which 
      induce lipid peroxidation in cell membranes and in low density lipoproteins, 
      mitochondrial membrane, secretion of cytochrome C and activation of caspase-3, 
      culminating in apoptosis. Thyroid hormones are known to have a profound effect on 
      CV functions. Hyperthyroidism causes heart rate, myocardial contractility and 
      ejection fraction to increase; this may result in systolic hypertension, systolic 
      heart murmurs, increased left ventricular weight and development of angina and 
      atrial fibrillation with a risk for stroke. AIM: The aim of our work was to 
      investigate into the special aspects that characterize implementation of 
      programmed cell death in circulating neutrophils of HHCy rats either without 
      comorbidities or with hyper- or hypothyroidism. MATERIALS AND METHODS: Prolonged 
      hyperthyroidism and hypothyroidism were modeled in experimental rats by dosing 
      the animals with Lthyroxine and thiamazole, respectively, for 21 days, and 
      prolonged with HHCy administered with excessive exogenous HCy, for 21 days. 
      Prolonged HHCy rats with hyper- or hypothyroidism were observed. RESULTS: We have 
      found the count of circulating neutrophils with increased ROS production and 
      reduced transmembrane mitochondrial potential to be significantly increased in 
      rats with HHCy compared to control animals, which suggests prooxidant properties 
      of HCy and its ability to cause mitochondrial dysfunction. The intensity of ROS 
      production by circulating neutrophils in hyperthyroid animals with HHCy was not 
      significantly different from that in hyperthyroid rats without HHCy. In 
      hypothyroid rats with HHCy, ROS production by circulating neutrophils was 
      significantly higher compared to the control group. HCys increased ROS generation 
      in kidney mitochondria while strongly decreasing it in liver, heart and brain 
      mitochondria showing that the changes are tissue-specific. We have found the 
      count of circulating neutrophils with signs of apoptosis to be increased in rats 
      with HHCy compared to the control group. CONCLUSIONS: Experimentally induced HHCy 
      is accompanied by hyperproduction of reactive oxygen species and by impaired 
      integrity of external mitochondrial membrane, which results in initiation of 
      apoptotic cell death. The deficiency of thyroid hormones enhances initiation of 
      programmed cell death.
CI  - (c) 2020 MEDPRESS.
FAU - Nechyporuk, Vitaliy
AU  - Nechyporuk V
AD  - National Pirogov Memorial Medical University, Vinnytsya, Ukraine.
FAU - Korda, Mykhailo
AU  - Korda M
AD  - I.Ya. Gorbachevsky Ternopil National Medical University of Moh, Ukraine.
FAU - Pentiuk, Larisa
AU  - Pentiuk L
AD  - National Pirogov Memorial Medical University, Vinnytsya, Ukraine.
FAU - Kovalchuk, Olena
AU  - Kovalchuk O
AD  - National Pirogov Memorial Medical University, Vinnytsya, Ukraine.
FAU - Andriichuk, Vitalii
AU  - Andriichuk V
AD  - National Pirogov Memorial Medical University, Vinnytsya, Ukraine.
LA  - eng
PT  - Journal Article
PL  - Poland
TA  - Pol Merkur Lekarski
JT  - Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego
JID - 9705469
RN  - 0 (Reactive Oxygen Species)
RN  - 0LVT1QZ0BA (Homocysteine)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Homocysteine
MH  - *Hyperhomocysteinemia/chemically induced/complications
MH  - Neutrophils
MH  - Rats
MH  - Reactive Oxygen Species
OTO - NOTNLM
OT  - hyperhomocysteinemia
OT  - hyperthyroidism
OT  - hypothyroidism
OT  - reactive oxygen species
EDAT- 2021/01/03 06:00
MHDA- 2021/01/06 06:00
CRDT- 2021/01/02 17:02
PHST- 2021/01/02 17:02 [entrez]
PHST- 2021/01/03 06:00 [pubmed]
PHST- 2021/01/06 06:00 [medline]
AID - PML288-437 [pii]
PST - ppublish
SO  - Pol Merkur Lekarski. 2020 Dec 22;48(288):437-442.