Open AccessEffect of Acetyl-l-carnitine Used for Protection of Neonatal Hypoxic-Ischemic Brain Injury on Acute Kidney Changes in Male and Female Rats
Author(s) -
Andrew G. Wang,
Michele Diamond,
Jaylyn Waddell,
Mary C. McKenna
Publication year - 2019
Publication title -
neurochemical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.102
H-Index - 116
eISSN - 1573-6903
pISSN - 0364-3190
DOI - 10.1007/s11064-019-02807-3
Subject(s) - carnitine , asphyxia , kidney , medicine , endocrinology , acute kidney injury , hypoxia (environmental) , ischemia , anesthesia , chemistry , oxygen , organic chemistry
Neonatal hypoxia-ischemia (HI) is a common cause of brain injury in infants. Acute kidney injury frequently occurs after birth asphyxia and is associated with adverse outcome. Treatment with acetyl-L-carnitine (ALCAR) after HI protects brain and improves outcome. Rat pups underwent carotid ligation and 75 min hypoxia on postnatal day 7 to determine effects of HI on kidney which is understudied in this model. HI + ALCAR pups were treated at 0, 4 and 24 h after HI. The organic cation/carnitine transporter 2 (OCTN2), transports ALCAR and functions to reabsorb carnitine and acylcarnitines from urine. At 24 h after injury OCTN2 levels were significantly decreased in kidney from HI pups, 0.80 ± 0.04 (mean ± SEM, p < 0.01), compared to sham controls 1.03 ± 0.04, and HI + ALCAR pups 1.11 ± 0.06. The effect of HI on the level of pyruvate dehydrogenase (PDH) was determined since kidney has high energy requirements. At 24 h after HI, kidney PDH/β-actin ratios were significantly lower in HI pups, 0.98 ± 0.05 (mean ± SEM, p < 0.05), compared to sham controls 1.16 ± 0.06, and HI + ALCAR pups 1.24 ± 0.03, p < 0.01. Treatment of pups with ALCAR after HI prevented the decrease in renal OCTN2 and PDH levels at 24 h after injury. Protection of PDH and OCTN2 after HI would improve energy metabolism in kidney, maintain tissue carnitine levels and overall carnitine homeostasis which is essential for neonatal health.