Mild Therapeutic Hypothermia Protects from Acute and Chronic Renal Ischemia-Reperfusion Injury in Mice by Mitigated Mitochondrial Dysfunction and Modulation of Local and Systemic Inflammation - Archive ouverte HAL Access content directly
Journal Articles International Journal of Molecular Sciences Year : 2022

Mild Therapeutic Hypothermia Protects from Acute and Chronic Renal Ischemia-Reperfusion Injury in Mice by Mitigated Mitochondrial Dysfunction and Modulation of Local and Systemic Inflammation

(1, 2) , (1) , (1) , (1) , (1) , (1) , (3) , (1) , (1, 2) , (1, 2) , (1) , (1, 2)
1
2
3
Maud Rabeyrin

Abstract

Renal ischemia-reperfusion (IR) injury can lead to acute kidney injury, increasing the risk of developing chronic kidney disease. We hypothesized that mild therapeutic hypothermia (mTH), 34 °C, applied during ischemia could protect the function and structure of kidneys against IR injuries in mice. In vivo bilateral renal IR led to an increase in plasma urea and acute tubular necrosis at 24 h prevented by mTH. One month after unilateral IR, kidney atrophy and fibrosis were reduced by mTH. Evaluation of mitochondrial function showed that mTH protected against IR-mediated mitochondrial dysfunction at 24 h, by preserving CRC and OX-PHOS. mTH completely abrogated the IR increase of plasmatic IL-6 and IL-10 at 24 h. Acute tissue inflammation was decreased by mTH (IL-6 and IL1-β) in as little as 2 h. Concomitantly, mTH increased TNF-α expression at 24 h. One month after IR, mTH increased TNF-α mRNA expression, and it decreased TGF-β mRNA expression. We showed that mTH alleviates renal dysfunction and damage through a preservation of mitochondrial function and a modulated systemic and local inflammatory response at the acute phase (2–24 h). The protective effect of mTH is maintained in the long term (1 month), as it diminished renal atrophy and fibrosis, and mitigated chronic renal inflammation.
Fichier principal
Vignette du fichier
2022_Schleef_Int_J_Mol_Sci.pdf (4.8 Mo) Télécharger le fichier
Origin : Publisher files allowed on an open archive

Dates and versions

hal-03789536 , version 1 (27-09-2022)

Licence

Attribution - CC BY 4.0

Identifiers

Cite

Maxime Schleef, Fabrice Gonnot, Bruno Pillot, Christelle Leon, Stéphanie Chanon, et al.. Mild Therapeutic Hypothermia Protects from Acute and Chronic Renal Ischemia-Reperfusion Injury in Mice by Mitigated Mitochondrial Dysfunction and Modulation of Local and Systemic Inflammation. International Journal of Molecular Sciences, 2022, 23 (16), pp.1-22. ⟨10.3390/ijms23169229⟩. ⟨hal-03789536⟩
10 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More