Invest Clin 65(2): 220 - 229, 2024 https://doi.org/10.54817/IC.v65n2a08

Corresponding Author: Halis Suleyman. Department of Pharmacology, Faculty of Medicine, Erzincan Binali Yildi-

rim University, 24100, Erzincan/Türkiye. Phone: +90 446 2261818, Fax: +90 446 2261819.

E-mail: halis.suleyman@gmail.com

Effect of thiamine pyrophosphate on

oxidative damage in the brain and heart

of rats with experimentally induced

occlusion of the common carotid artery.

Izzet Emir

,

Zeynep Suleyman

and Halis Suleyman

Erzincan/Türkiye.

3

Erzincan/Türkiye.

Keywords: carotid artery; ıschemia; occlusion; rat; reperfusion; thiamine pyrophosphate.

de tiamina.

Resumen. Se sabe que un aumento repentino del flujo sanguíneo cere-

y despinzamiento de la carótida común (TCCU) y operación simulada (SG).

sacrificados con altas dosis de anestesia y se extrajeron tejidos del corazón y

del cerebro. El TPP suprimió significativamente el aumento de malondialdehí-

do (MDA) inducido por I/R y la disminución de los niveles de glutatión total

(tGSH) tanto en el tejido cerebral como en el cardíaco. El TPP impidió el au-

1β (IL-1β) e interleucina-6 (IL-6) en los tejidos del cerebro y del corazón. En

dativo e inflamatorio inducido por la I/R cerebral.

cations that lead to death

1

. As known, ath-

erosclerotic carotid artery disease is a sig-

nificant cause of stroke worldwide

2

. Patients

with severe carotid artery stenosis (≥70%)

tion and cardiovascular death (22%)

3

4

During carotid endarterectomy, cross-clamp-

may disrupt and damage the blood-brain bar-

rier

. It is argued that this damage is due to

and polymorphonuclear leukocytes are im-

plicated in I/R-related distant organ injury

9,10

. The neutrophil-to-lymphocyte ratio is

recognized as a marker for systemic inflam-

mation and is significantly associated with

postoperative complications

11

. Myocardial

injury that may develop due to reperfusion.

Myocardial ischemia and hypoxia have been

associated with abnormal increases in TPI

13

levels of TPI and CK-MB are also positively

correlated with elevated levels of oxidants

and pro-inflammatory cytokines

.

tive metabolite of thiamine

15

, is synthesized

in the liver through the phosphorylation of

thiamine by thiamine pyrophosphokinase

16

Existing literature suggests that TPP exerts a

17

ing. There is a lack of literature investigat-

ing the potential impact of TPP on cardiac

and unclamping procedures. Hence, our

study aimed to biochemically explore TPP’s

protective effects against potential brain

and heart damage from animal carotid cross-

alent volume of distilled water as a solvent

via the IP route. General anesthesia was

induced with 60 mg/kg of ketamine hydro-

chloride via the IP route. The period during

which the animals remain immobile in the

supine position is considered a suitable an-

esthesia period for surgical intervention

midline incision was made. After a superfi-

tery. The trachea was exposed, paratracheal

six hours. Subsequently, the rats were eutha-

nized with high-dose anesthesia. The levels

of oxidant/antioxidant markers, including

one (tGSH), as well as pro-inflammatory cy-

tokines tumor necrosis factor-alpha (TNF-α),

interleukin-6 (IL-6), and interleukin 1β (IL-

1β), were measured in the extracted brain

and heart tissue samples. Troponin I (TP I)

Biochemical analyses

Preparation of Samples

physiological saline, they were ground into

Quantification of MDA and GSH,

and Protein Levels

heart tissues were quantified following the

(ELISA) kit instructions of the respective

assays (Cayman Chemical Company). Pro-

tein was detected according to the Bradford

enized by adding liquid nitrogen. We then

added phosphate-buffered saline (pH 7.4)

in a 1/10 (w/v) ratio and vortexed, followed

by centrifugation for 15 min at 15000×g

to collect the supernatant. The samples

were maintained at 2-8°C after melting.

The TNF-α, IL-1β, and IL-6 levels were de-

(CK-MB) Determination

using the enzyme-linked fluorescent assay

technique with the VIDAS TPI Ultra kit and

kit. The Roche/Hitachi Cobas C 701 system

Statistical Analyses

SD). The normality test in the groups was

ed to be significant.

RESULTS

Pro-inflammatory cytokines levels in brain

tissue

than in the sham group (p<0.001). TPP ad-

= 0.021; p = 0.001; p = 0.034).

Oxidant/Antioxidant levels in heart tissue

mals were significantly higher in the CCU

(p<0.001) (Table 1).

Pro-inflammatory levels in heart tissue

(p<0.001). TNF-α and IL-1β levels between

(p = 0.184).

ly decreased compared to those in the CCU

0.550) (Table 1).

DISCUSSION

22,23

nisms are responsible for the pathogenesis

24

of lipid peroxidation (LPO)

25

. MDA is a bio-

age

I/R model induced by the common carotid

due to cerebral I/R are associated with neu-

21,26

istration of TPP to rats significantly sup-

amine the protective effect of TPP against

artery occlusion. Yasar et al. reported that

brain damage caused by focal I/R

I/R, owing to its antioxidant properties.

29,31

ies have associated decreased GSH levels

LPO

. Sharipov et al. reported oxidative

damage in the heart mitochondria of rats in

24

tGSH levels in both brain and heart tissue,

that tGSH cannot counteract the elevated

ROS levels of I/R. However, TPP significantly

suppressed the I/R injury-related decrease in

rats, which is consistent with previous find-

distant cardiac tissue damage due to cere-

bral I/R by inhibiting LPO and preserving

the antioxidant system.

Ischemia, followed by reperfusion, dis-

IL-6

is the primary cytokine responsible for stim-

mately leading to cell death

24

. Consistent

TNF-α, IL-1β, and IL-6 levels in both brain

et al.

to focal I/R injury, there is no study showing

the protective effect of TPP against distant

occlusion procedure led to an increase in se-

increase in TPI and CK-MB levels explains

heart tissue damage and reflects the impact

of the brain I/R event on the heart tissue.

In the literature, abnormal elevation of TPI

another study

37

and pro-inflammatory cytokines.

artery occlusion increased pro-inflammato-

TPP protects the brain and distant cardiac

duces cardiac damage. The most significant

limitations of this study include the absence

of common carotid occlusion monitoring

and the lack of histopathological examina-

tions. Further studies are necessary to clari-

fy the role of TPP in preventing cerebral I/R

ACKNOWLEDGMENTS

Thanks to Taha Abdulkadir Coban for

the biochemical analysis of data.

None.

ORCID number of authors

• Izzet Emir (IE):

0000-0002-1098-4889

sition of data: TAC; Analysis and interpreta-

IE, HS; Critical revision of the manuscript

for important intellectual content: HS; Sta-

tistical analysis: ZS; Final approval of the

submitted manuscript: IE, ZS, HS, TAC.