• Biomolecules & Therapeutics
• /
• 제28권5호
• /
• pp.381-388
• /
• 2020

Methamphetamine (METH) is a highly addictive psychostimulant and one of the most widely abused drugs worldwide. The continuous use of METH eventually leads to drug addiction and causes serious health complications, including attention deficit, memory loss and cognitive decline. These neurological complications are strongly associated with METH-induced neurotoxicity and neuroinflammation, which leads to neuronal cell death. The current review investigates the molecular mechanisms underlying METH-mediated neuronal damages. Our analysis demonstrates that the process of neuronal impairment by METH is closely related to oxidative stress, transcription factor activation, DNA damage, excitatory toxicity and various apoptosis pathways. Thus, we reach the conclusion here that METH-induced neuronal damages are attributed to the neurotoxic and neuroinflammatory effect of the drug. This review provides an insight into the mechanisms of METH addiction and contributes to the discovery of therapeutic targets on neurological impairment by METH abuse.

• 생명과학회지
• /
• 제16권2호
• /
• pp.266-273
• /
• 2006

MPTP에 의해 유도된 Parkinsonism에 대한 selenium의 보호효과와 그 보호작용에 대한 항산화적 해독기전을 조사하기 위하여 MPTP 10mg/kg을 6일간 주사하고 selenium (25, 50, 100 ${\mu}g/kg$)을 10일간 경구 투여하였으며 처음 6일간은 selenium와 MPTP를 병용 투여하였다. 실험동물을 마지막으로 selenium을 투여하고 24시간 후에 치사시켜 일반적인 독성과 항산화 방어능과 관련된 지표성분과 monoamine oxidase와 같은 신경생화학적인 지표성분들을 뇌조직에서 측정하였으며 그 결과 다음과 같은 결론을 얻었다. 우선 MPTP를 투여함에 따라 운동능력이 저하되던 것이 selenium을 투여함에 따라 운동능력이 증가되었으며, 이러한 결과의 기전은 selelnium을 투여함으로써 MPTP를 $MPP^+$로 대사시키는 MAO-B의 활성을 억제하였으며 $MPP^+$에 의해 유도된 신경독성에 대한 selenium의 보호 효과는 selenium을 투여함으로써 활성산소 해독계인 SOD, catalase, glutathione peroxidase의 활성을 증가시키기 때문인 것으로 사료된다.

• Biomolecules & Therapeutics
• /
• 제22권6호
• /
• pp.532-539
• /
• 2014

Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC ($50{\mu}mol/L$), gp120 (500 pmol/L) plus ddC ($50{\mu}mol/L$), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC ($50{\mu}mol/L$) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC ($50{\mu}mol/L$) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (> $25{\mu}m$), whereas ddC mainly affected small diameter DRG neurons (${\leq}25{\mu}m$). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.

• 대한임상검사과학회지
• /
• 제50권4호
• /
• pp.501-510
• /
• 2018

본 연구는 배양 C6 glioma 세포를 대상으로 초산납(lead acetate, LA)의 신경독성을 알아보았으며, 또한 LA의 세포독성에 대한 지금초(Euphorbiae humifusae L., EH) 추출물의 영향을 조사하였다. 본 연구에서, LA는 대조군에 비하여 농도 의존적으로 세포 생존율이 감소됨으로서 신경독성을 보였으며, $0{\sim}50{\mu}M$의 LA가 각각 포함된 배양액에서 72시간 동안 세포를 처리한 결과, $XTT_{50}$ 값은 $38.6{\mu}M$로 고독성인 것으로 나타났다. 또한, $30{\sim}50{\mu}M$의 LA가 각각 포함된 배양액에서 72시간 동안 세포를 처리한 결과 $XTT_{50}$은 $38.6{\mu}M$에서 나타났다. 이와 동시에 항산화제인 vitamin E의 처리에서 LA 독성에 의하여 감소된 세포 생존율이 유의하게 증가함으로서 LA의 독성에 산화적 손상이 관여하고 있음을 제시하였다. 한편, EH 추출물은 지질과산화 저해능을 비롯하여 superoxide dismutase (SOD)-유사활성능 및 DPPH-라디칼 소거능과 같은 항산화능에 의하여 LA 독성을 효과적으로 방어하였다. 이같은 항산화 효과는 gallic acid와 같은 폴리페놀이나 또는 flavonol이나 quercetin과 같은 플라보노이드와 같은 항산화성분에 기인된 결과로 생각된다. 결론적으로, EH 추출물과 같은 천연 소재는 차후 납신경독성과 같이 산화적 손상과 관련된 질환 치료를 위한 유용한 활용 인자로 사료된다.

• 한국환경성돌연변이발암원학회:학술대회논문집
• /
• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
• /
• pp.188-189
• /
• 2002

• 한국환경독성학회:학술대회논문집
• /
• 한국환경독성학회 2004년도 춘계학술대회
• /
• pp.76-76
• /
• 2004

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
• /
• pp.188-189
• /
• 2002

This work aimed to identify neuronal cell toxicity induced by decrease of physiological NO production by differential phosphorylation of constitutive neuronal NO synthase (nNOS), which can be mediated by Ca2+-dependent PKC and/or CaM-KII activities activated by metals.(omitted)

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2002년도 Current Trends in Toxicological Sciences
• /
• pp.89-89
• /
• 2002

It is well known that oxygen radicals induce neuronal cell damage by initiation of lipid peroxidation chain reaction. Recent work has been also demonstrated that enzymatically generated free radicals cause the release of glutamate and aspartate from cultured rat hippocampal slices.(omitted)

• 동의생리병리학회지
• /
• 제16권1호
• /
• pp.146-149
• /
• 2002

To evaluate the protective effect of Ziziphi Jujubae Semen(ZJS) on 5-Fluorouracil(5-Fu) in cultured vestibular neurons(VN), neurotoxicity was assessed by XTT assay after VN was exposed to 3-24ug/ml 5-Fu for 48 hours. and also, the neuroprotective effect of ZJS was measured by XTT assay in these cultrures. Cell viability was remarkably decreased dose-dependently, after the treatment with 12ug/ml 5-Fu to cultured VN for 48 hours. In the neuroprotective effect of ZJS on the toxicity induced by 5-Fu, ZJS prevented the neurotoxicity induced by 5-Fu in these cultures. From above the results, it suggests that 5-Fu is toxic in cultured VN and herb extract, ZJS has protective effect over the neurotoxicity induced by 5-Fu.

• 동의생리병리학회지
• /
• 제16권5호
• /
• pp.928-931
• /
• 2002

To elucidate the toxic effect of oxygen free radicals on cultured mouse cerebral neurons damaged by hydrogen peroxide(H₂O₂)-induced neurotoxicity, we examined the neurotoxicity induced by oxygen radicals by NR assay when cultured cerebral neurons were grown in the media containing various concentrations of H202 for 6 hours. In addition, neuroprotective effects of herb extracts such Rhizoma Gastrodiae(RG) on H202-induced neurotoxicity in cultured cerebral neurons were evaluated after cultured cerebral neurons were preincubated with various concentrations of herb extract, RG for 2 hours before 50uM H₂O₂ for 6 hours. H₂O₂ decreased remarkably cell viability in dose-and time-dependent manner in these cultures, and also herb exract, RG decreased LDH activity of cerebral neurons damaged by H₂O₂. From the above results, it is suggested that H₂O₂ was toxic in cultured cerebral neurons from mouse, and RG was effective in blocking the neurotoxicity induced by oxygen radicals in these cultures.