The effects of isoniazid on hippocampal NMDA receptors: Protective role of Erdosteine

Abstract

Isoniazid (INH) has neurotoxic effects such as seizure, poor concentration, subtle reduction in memory, anxiety, depression and psychosis. INH-induced toxic effects are thought to be through increased oxidative stress, and these effects have been shown to be prevented by antioxidant therapies in various organs. Increased oxidative stress may be playing a role in these neurotoxic effects. N-methyl D-aspartat receptors (NMDA) are a member of the ionotropic group of glutamate receptors. These receptors are involved in a wide variety of processes in the central nervous system including synaptogenesis, synaptic plasticity, memory and learning. Erdosteine is a potent antioxidant and mucolytic agent. We aimed to investigate adverse effects of INH on rat hippocampal NMDAR receptors, and to elucidate whether erdosteine prevents possible adverse effects of INH. In the present study, compared to control group, NMDAR2A (NR2A) receptors were significantly decreased and malondialdehyde (MDA), end product of lipid peroxidation, production was significantly increased in INH-treated group. On the other hand, administration of erdosteine to INH-treated group significantly increased NR2A receptors and decreased MDA production. In conclusion, decreasing NR2A receptors in hippocampus and increasing lipid peroxidation correlates with the degree of oxidative effects of INH and erdosteine protects above effect of INH on NR2A receptors and membrane damage due to lipid peroxidation by its antioxidant properties.

Acute psychotic attack under isoniazid treatment: a case report

“…Similar to cases and review in the literature, paranoid delusions were determined prominently in our case. It was determined that INH decreased number of N-methyl-D-aspartate (NMDA) receptors in the hippocampus, and this effect was abolished by addition of erdostein which was an antioxidant molecule in a study performed to enlighten the relationship INH and psychiatric disorders, and with the hypothesis of INH might have toxic effects on oxidative stress (9).…”

Anxious phenotypes plus environmental stressors are related to brain DNA damage and changes in NMDA receptor subunits and glutamate uptake

“…Cicek et al [10] demonstrated that isoniazid, which is known to be neurotoxic, induced a decrease in NR2A levels in the hippocampus that was correlated to an increase in lipid peroxidation, and that endosteine, which is an antioxidant, was able to reverse these effects. In addition, mice carrying a mutation at the Tyr 1325 phosphorylation site, which is largely found in NR2A, showed reduced depression-related behavior [62], suggesting that NR2A may be an important target in studying the pathogenesis of mood disorders and in developing therapeutic drugs.…”

Effects Of Erdosteine On Oxidative-Antioxidative Equilibrium And On Cataract Formation In Rat Pups With Selenite-Induced Cataract

“…It is a potent antioxidant and mucolytic pharmacological agent (24,25). Erdosteine inhibits lipid peroxidation (25).…”

“…Erdosteine inhibits lipid peroxidation (25). The pharmacological agent, therefore, decreases malondialdehyde (MDA), which is the end product of lipid peroxidation (24). Furthermore, erdosteine maintains free radical scavenging properties (25).…”