The Protective and Restorative Effects of Growth Hormone and Insulin-Like Growth Factor-1 on Methadone-Induced Toxicity In Vitro

Abstract

Evidence to date suggests that opioids such as methadone may be associated with cognitive impairment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are suggested to be neuroprotective and procognitive in the brain and may therefore counteract these effects. This study aims to explore the protective and restorative effects of GH and IGF-1 in methadone-treated cell cultures. Primary cortical cell cultures were harvested from rat fetuses and grown for seven days in vitro. To examine the protective effects, methadone was co-treated with or without GH or IGF-1 for three consecutive days. To examine the restorative effects, methadone was added for the first 24 h, washed, and later treated with GH or IGF-1 for 48 h. At the end of each experiment, mitochondrial function and membrane integrity were evaluated. The results revealed that GH had protective effects in the membrane integrity assay and that both GH and IGF-1 effectively recovered mitochondrial function and membrane integrity in cells pretreated with methadone. The overall conclusion of the present study is that GH, but not IGF-1, protects primary cortical cells against methadone-induced toxicity, and that both GH and IGF-1 have a restorative effect on cells pretreated with methadone.

Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial

“…although not fully understood, could be mediated by modifying the action of prooxidative enzymes such as NOX4. This is in agreement with previous studies that have demonstrated that GH has a protective effect on mitochondria [38,39], which are the main source of oxidants within cells. This is the reason why mitochondrial dysfunction leads to a greater generation of hROS, which, in turn, contributes to the presentation of a senescent phenotype in ECs and to the activation of redox-sensitive transcription factor nuclear factor-kappa B (NF-κB) [40], which decreases endothelium-induced vasodilation and increases the expression of inflammatory genes in the vasculature of aged rats and elderly humans [41,42].…”

Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial

“…This is what happens in patients with GHD, but it is normalized after replacement therapy with GH [13]. This is in agreement with previous studies that demonstrate that GH has a protective effect on mitochondria [41,42], which are the main source of oxidants within cells and a main objective of oxidative stress, but also produce elimination systems of oxidants. This is the reason why mitochondrial dysfunction leads to a greater generation of hROS which, in turn, contributes to the presentation of a senescent phenotype in ECs and to the activation of redox-sensitive transcription factor NF-kß [43], that decreases endothelialinduced vasodilation and increases the expression of inflammatory genes in the vasculature of aging rats and humans [44,45].…”

The role of serum growth hormone and insulin-like growth factor-1 in adult humans brain morphology

“…Meanwhile, GH and IGF-1 in circulation have been shown to cross the blood-brain barrier into the brain tissue and cerebrospinal fluid (CSF) to activate GH/IGF-1 receptors [3,[6][7][8]. The potential roles of GH and IGF-1 in brain growth, development, neurogenesis, and neuroprotection, as well as their functional roles in behavior, cognition and neurotransmission, have been investigated in vivo and in vitro [9][10][11][12]. For instance, GH or IGF-1 gene knock-out mice, compared to control animals, exhibited CNS deficits including reduced brain size, loss of myelination and specific parvalbumincontaining neurons, and cognitive impairments [13,14].…”