Melatonin attenuates methamphetamine-induced overexpression of pro-inflammatory cytokines in microglial cell lines.
Methamphetamine (METH), the most commonly abused drug, has long been known to induce neurotoxicity. METH causes oxidative stress and inflammation, as well as the overproduction of both reactive oxygen species (ROS) and reactive nitrogen species (RNS). The role of METH-induced brain inflammation remains unclear. Imbroglio activation contributes to the neuronal damage that accompanies injury, disease and inflammation. METH may activate microglia to produce neuroinflammatory molecules. In highly aggressively proliferating immortalized (HAPI) cells, a rat microglial cell line, METH reduced cell viability in a concentration- and time-dependent manner and initiated the expression of interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and tumor necrosis factor alpha. METH also induced the production of both ROS and RNS in microglial cells. Pretreatment with melatonin, a major secretory product of the pineal gland, abolished METH-induced toxicity, suppressed ROS and RNS formation and also had an inhibitory effect on cytotoxic factor gene expression. The expression of cytotoxic factors produced by microglia may contribute to central nervous system degeneration in amphetamine abusers. Melatonin attenuates METH toxicity and inhibits the expression of cytotoxic factor genes associated with ROS and RNS neutralization in HAPI microglia. Thus, melatonin might be one of the neuroprotective agents induced by METH toxicity and/or other immunogens.
Tocharus
Jiraporn
J
Department of Biochemistry, Naresuan University, Phitsanulok, Thailand.
Khonthun
Chakkrapong
C
Chongthammakun
Sukumal
S
Govitrapong
Piyarat
P
D000704:Analysis of Variance; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D008550:Melatonin / Q000494:pharmacology*; D008694:Methamphetamine / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D008694:Methamphetamine; D008550:Melatonin