PhD Scientific Days 2020

Molecular Sciences V. Lectures

Long-term Effects of Perinatal Asphyxia on Multi-organ Injury

Előadó neve

Tóth, Ákos Roland

Előadó munkahelye

Semmelweis University 1 st Department of Pediatrics

Előadó telefonszáma

+36706604784

Előadó e-mail címe

akostoth95@gmail.com

Az előadás címe

Long-term Effects of Perinatal Asphyxia on Multi-organ Injury

Szerző(k) neve és munkahelye

A. R. Toth1; T. Lakat1,2; A. Molnar1;; K. Demeter6; H. Kelemen2,3; E Mikics3; A. J. Szabo2,4; A. Dénes5; A. Fekete1,2; A. Hosszu1,2

1MTA-SE “Lendület” Diabetes Research Group, Budapest, Hungary
2Semmelweis University 1st Department of Pediatrics, Budapest, Hungary
3Laboratory of Translational Behavioural Neuroscience, Institute of Experimental Medicine, Budapest, Hungary
4MTA-SE Pediatrics and Nephrology Research Group, Budapest, Hungary
5Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary
6Behavioral Studies Unit, Institute of Experimental Medicine, Budapest, Hungary

Szekció

Molecular Sciences V. Lectures

Language of the presentation

English

Section, first choice

Molecular Sciences

Section, second choice

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction:
Detrimental effects of perinatal asphyxia (PA) are mainly associated with the complications of hypoxic encephalopathy. In a parallel experiment we showed signs of acute renal- hepatic- and cardiovascular injury following PA, however, long-term outcome of multi-organ damage is poorly investigated, clinical follow-up data is lacking. PA adults may be more vulnerable in conditions where ischemia/reperfusion (IR) injury occurs, such as transplantation, major surgeries, infarction or sepsis.

Aims:
The aim of the present study was to investigate long-term effects of PA on permanent organ damage and susceptibility to IR injury in adulthood.

Method:
35 min bilateral renal IR insult was performed on male Wistar rats at 6 months of age (n=6-7/group). The groups were the following: (i) Control; (ii) PA (postnatal day 7; 4% O2; 20% CO2 in N2 gas mixture; 15 mins; 37oC) + SHAM; (iii) IR; (iv) PA+IR. Serum and tissue samples were collected 24 hours after reperfusion. Serum levels of electrolytes, kidney and liver functional parameters were determined. Highly selective tubular injury markers (Kim1, Ngal) were measured. Expressions of hypoxic (Hif1α, Hif2α), inflammatory (Il1α, Il1β, Il6), apoptotic (Bax, Bcl-2), angiogenic genes (Vegf, Epo) and profibrotic (Tgfβ, Pdgf, Ctgf) were investigated. Periodic-Acid Schiff staining on kidney tissue sections, and Hematoxylin & Eosin staining on liver tissue sections were performed.

Results:
In PA rats BUN levels were elevated at the age of 6 months, suggesting a long-term impact of PA. In addition, adult PA rats were more sensitive to renal ischemic insult, confirmed by higher serum creatinine, as well as increased renal expressions of Ngal, Hif1α, Epo, Il6 and Bcl-2 in PA+IR vs. IR. No long-term effect of PA was observed in the liver. However, serum GPT levels and liver Il1β expression were higher in the PA+IR than in the IR group.

Conclusion:
Long-term detrimental effects of PA on kidney and liver function were observed. In addition, birth asphyxia may increase sensitivity to renal- and hepatic injury even in adulthood, which may be worth considering in clinical situations with potential renal impairment such as major surgeries. Multiple activated pathways may be potential targets of novel therapeutic drug development, which may offer substantial benefits over current first-line therapy.

Additional Information

Supervisor: Ádám Hosszú
E-mail address: hosszu.adam@gmail.com

Grants: NN OTKA-114607, VKE-2017-00006, FK124491

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4764

Start

17:45

End

18:00

Authors (legacy)

A. R. Toth1; T. Lakat1,2; A. Molnar1;; K. Demeter6; H. Kelemen2,3; E Mikics3; A. J. Szabo2,4; A. Dénes5; A. Fekete1,2; A. Hosszu1,2

1MTA-SE “Lendület” Diabetes Research Group, Budapest, Hungary
2Semmelweis University 1st Department of Pediatrics, Budapest, Hungary
3Laboratory of Translational Behavioural Neuroscience, Institute of Experimental Medicine, Budapest, Hungary
4MTA-SE Pediatrics and Nephrology Research Group, Budapest, Hungary
5Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary
6Behavioral Studies Unit, Institute of Experimental Medicine, Budapest, Hungary