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Estimation of an area between the baseline and the effect curve parameter for lactate levels in the hippocampi of neonatal rats during anesthesia. / Bannova, Anita V.; Akulov, Andrey E.; Menshanov, Petr N. et al.
In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 150, 20.02.2018, p. 327-332.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Estimation of an area between the baseline and the effect curve parameter for lactate levels in the hippocampi of neonatal rats during anesthesia
AU - Bannova, Anita V.
AU - Akulov, Andrey E.
AU - Menshanov, Petr N.
AU - Dygalo, Nikolay N.
N1 - Publisher Copyright: © 2017 Elsevier B.V.
PY - 2018/2/20
Y1 - 2018/2/20
N2 - Naturally occurring caspase-3-dependent cell death is a widespread event in the immature nervous system. Prolonged exposure to anesthetics promotes activation of caspase-3 in the developing hippocampus. In addition, anesthetics can upregulate the levels of metabolite lactate in the adult brain. The long-lasting increase in lactate levels may affect viability of brain cells. However, it remains unknown if anesthetic-induced activation of caspase-3 is accompanied by an increase in lactate levels in the immature brain. We investigated expression of apoptotic proteins by immunoblot and estimated an area between the baseline and the effect curve (ABEC) parameter for lactate levels by high-resolution magnetic resonance spectroscopy in the hippocampi of 2-day-old Wistar rats after treatment with anesthetic urethane. Both 1.5 and 2.5 g/kg of urethane resulted in a dose-dependent increase in the levels of active caspase-3 in the hippocampi in 4 h after injection. This anesthetic-induced increase in the levels of active caspase-3 was preceded by a prolonged dose-dependent rise in lactate levels. The dose-dependent increase in lactate levels was not associated with the urethane-induced changes in respiratory rate in the treated rat pups. Present results evidence that the prolonged dose-dependent elevation in lactate levels in the developing brain can be induced even by urethane, which was suggested to be suitable for various physiopharmacological studies previously. The observed sequence of events after treatment with urethane suggests the possible role of lactate as a neurodamaging agent in the immature brain in case of the sustaining rise in the levels of this metabolite during prolonged anesthesia.
AB - Naturally occurring caspase-3-dependent cell death is a widespread event in the immature nervous system. Prolonged exposure to anesthetics promotes activation of caspase-3 in the developing hippocampus. In addition, anesthetics can upregulate the levels of metabolite lactate in the adult brain. The long-lasting increase in lactate levels may affect viability of brain cells. However, it remains unknown if anesthetic-induced activation of caspase-3 is accompanied by an increase in lactate levels in the immature brain. We investigated expression of apoptotic proteins by immunoblot and estimated an area between the baseline and the effect curve (ABEC) parameter for lactate levels by high-resolution magnetic resonance spectroscopy in the hippocampi of 2-day-old Wistar rats after treatment with anesthetic urethane. Both 1.5 and 2.5 g/kg of urethane resulted in a dose-dependent increase in the levels of active caspase-3 in the hippocampi in 4 h after injection. This anesthetic-induced increase in the levels of active caspase-3 was preceded by a prolonged dose-dependent rise in lactate levels. The dose-dependent increase in lactate levels was not associated with the urethane-induced changes in respiratory rate in the treated rat pups. Present results evidence that the prolonged dose-dependent elevation in lactate levels in the developing brain can be induced even by urethane, which was suggested to be suitable for various physiopharmacological studies previously. The observed sequence of events after treatment with urethane suggests the possible role of lactate as a neurodamaging agent in the immature brain in case of the sustaining rise in the levels of this metabolite during prolonged anesthesia.
KW - Active caspase-3
KW - Anesthetics
KW - Developing hippocampus
KW - Lactate
KW - Magnetic resonance spectroscopy
KW - Urethane
KW - APOPTOSIS
KW - ENERGY
KW - ISOFLURANE
KW - ACIDOSIS
KW - DEVELOPING BRAIN
KW - SPECTROSCOPY
KW - METABOLISM
KW - IN-VIVO
KW - VOLATILE ANESTHETICS
KW - EXPOSURE
KW - Up-Regulation
KW - Anesthesia, General
KW - Caspase 3/metabolism
KW - Rats, Wistar
KW - Urethane/administration & dosage
KW - Dose-Response Relationship, Drug
KW - Time Factors
KW - Hippocampus/drug effects
KW - Anesthetics, Intravenous/administration & dosage
KW - Animals, Newborn
KW - Magnetic Resonance Spectroscopy
KW - Animals
KW - Lactic Acid/metabolism
UR - http://www.scopus.com/inward/record.url?scp=85038878725&partnerID=8YFLogxK
U2 - 10.1016/j.jpba.2017.12.021
DO - 10.1016/j.jpba.2017.12.021
M3 - Article
C2 - 29277066
AN - SCOPUS:85038878725
VL - 150
SP - 327
EP - 332
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
SN - 0731-7085
ER -
ID: 9159913