Paraquat induces redox imbalance and disrupts glutamate and energy metabolism in the hippocampus of prepubertal rats.
Neurotoxicology
; 85: 121-132, 2021 07.
Article
em En
| MEDLINE
| ID: mdl-34048864
Paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride; PQ) is a widely used herbicide in Brazilian crops, despite its banishment in many other countries. The present study investigated the effects of repeated dose of PQ on glutamate system, energy metabolism and redox parameters in the hippocampus of prepubertal rats. Twenty-two-day-old rats received daily intraperitoneal injections of PQ (10 mg/Kg) during 5 consecutive days and the effects of the pesticide were assessed 24 h after the last injection. The PQ exposure provoked cytotoxicity associated to decreased cell viability and increased glutamate excitotoxicity, as demonstrated by decreased 14C-glutamate uptake and increased 45Ca2+ uptake. Downregulated glutamine synthetase (GS) activity, further supports disrupted glutamate metabolism compromising the glutamate-glutamine cycle. Downregulated 14C-2-Deoxy-D-glucose indicates energy failure and upregulated lactate dehydrogenase (LDH) suggests the relevance of lactate as energy fuel. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) upregulation suggest Krebs cycle replenishment and piruvate production. In addition, PQ disturbed the redox status inducing lipid peroxidation, evaluated by increased TBARS and imbalanced antioxidant system. Downregulated glutathione reductase (GR), gamma-glutamyltransferase (GGT), glutathione-S-transferase (GST) and glucose-6-P-dehydrogenase (G6PD) activities together with upregulated superoxide dismutase (SOD) and catalase activities corroborate the oxidative imbalance. The mechanisms underlying PQ-induced neurotoxicity involves the modulation of GSK-3ß, NF-κB and NMDA receptors. These neurochemical and oxidative events observed may contribute to neuroinflammation and neurotoxic effects of PQ on hippocampal cells.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Paraquat
/
Maturidade Sexual
/
Ácido Glutâmico
/
Metabolismo Energético
/
Herbicidas
/
Hipocampo
Limite:
Animals
Idioma:
En
Revista:
Neurotoxicology
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Holanda