TY - JOUR
T1 - Effects of Hypothermia and Allopurinol on Oxidative Status in a Rat Model of Hypoxic Ischemic Encephalopathy
AU - Durán Fernández-Feijóo, Cristina
AU - Rodríguez-Fanjul, Javier
AU - Lopez-Abat, Miriam
AU - Hadley, Stephanie
AU - Cavia, Mónica
AU - Muñiz, Pilar
AU - Arnaez, Juan
AU - Fernández-Lorenzo, José Ramón
AU - Camprubí Camprubí, Marta
PY - 2021
Y1 - 2021
N2 - Hypoxic ischemic encephalopathy (HIE) is one of the main causes of morbidity and mortality during the neonatal period, despite treatment with hypothermia. There is evidence that oxidative damage plays an important role in the pathophysiology of hypoxic-ischemic (HI) brain injury. Our aim was to investigate whether postnatal allopurinol administration in combination with hypothermia would reduce oxidative stress (OS) biomarkers in an animal model of HIE. Postnatal 10-day rat pups underwent unilateral HI of moderate severity. Pups were randomized into: Sham operated, hypoxic-ischemic (HI), HI + allopurinol (HIA), HI + hypothermia (HIH), and HI + hypothermia + allopurinol (HIHA). Biomarkers of OS and antioxidants were evaluated: GSH/GSSG ratio and carbonyl groups were tested in plasma. Total antioxidant capacity (TAC) was analyzed in plasma and cerebrospinal fluid, and 8-iso-prostaglandin F2α was measured in brain tissue. Plasma 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) levels were preserved in those groups that received allopurinol and dual therapy. In cerebrospinal fluid, only the HIA group presented normal ferric reducing ability of plasma (FRAP) levels. Protein oxidation and lipid peroxidation were significantly reduced in all groups treated with hypothermia and allopurinol, thus enhancing neuroprotection in HIE.
AB - Hypoxic ischemic encephalopathy (HIE) is one of the main causes of morbidity and mortality during the neonatal period, despite treatment with hypothermia. There is evidence that oxidative damage plays an important role in the pathophysiology of hypoxic-ischemic (HI) brain injury. Our aim was to investigate whether postnatal allopurinol administration in combination with hypothermia would reduce oxidative stress (OS) biomarkers in an animal model of HIE. Postnatal 10-day rat pups underwent unilateral HI of moderate severity. Pups were randomized into: Sham operated, hypoxic-ischemic (HI), HI + allopurinol (HIA), HI + hypothermia (HIH), and HI + hypothermia + allopurinol (HIHA). Biomarkers of OS and antioxidants were evaluated: GSH/GSSG ratio and carbonyl groups were tested in plasma. Total antioxidant capacity (TAC) was analyzed in plasma and cerebrospinal fluid, and 8-iso-prostaglandin F2α was measured in brain tissue. Plasma 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) levels were preserved in those groups that received allopurinol and dual therapy. In cerebrospinal fluid, only the HIA group presented normal ferric reducing ability of plasma (FRAP) levels. Protein oxidation and lipid peroxidation were significantly reduced in all groups treated with hypothermia and allopurinol, thus enhancing neuroprotection in HIE.
KW - Allopurinol
KW - Hypothermia
KW - Hypoxic-ischemic encephalopathy
KW - Oxidative stress
KW - Oxidative damage
U2 - 10.3390/antiox10101523
DO - 10.3390/antiox10101523
M3 - Article
C2 - 34679658
SN - 2076-3921
VL - 10
JO - Antioxidants
JF - Antioxidants
IS - 10
ER -