Exacerbation of Methamphetamine Neurotoxicity in Cold and Hot Environments: Neuroprotective Effects of an Antioxidant Compound H-290/51

Abstract

In this study, we examined the influence of cold and hot environments on methamphetamine (METH) neurotoxicity in both drug-naive rats and animals previously exposed to different types of nanoparticles (NPs). Since METH induces oxidative stress, we also examined how a potential chain-braking antioxidant H-290/51 (Astra-Zeneca Mölndal, Sweden) affects METH-induced neurotoxicity. Exposure of drug-naive rats to METH (9 mg/kg, s.c.) at 4°, 21° or 34°C for 3 hrs resulted in breakdown of the blood-brain barrier (BBB), brain edema and neuronal injuries, which all differed in their extent depending upon ambient temperatures. The changes were moderate at 21°C, 120–180% larger at 34°C, and almost absent at 4°C. In rats chronically treated with NPs (SiO2, Cu or Ag; 50–60 nm, 50 mg/kg, i.p. for 7 days), METH-induced brain alterations showed a 2- to 4-fold increase in brain pathologies after METH at 21°C; 4-to 6-fold increase at 34°C and 3- to 4-fold increase at 4°C. SiO2 exposure showed the most pronounced METH-induced brain pathology at all temperature ranges followed by Ag and Cu NPs. Pretreatment with a potent antioxidant compound H-290/51 (50 mg/kg, p.o. 30 min before METH) significantly reduced brain pathology in naive animals exposed to METH at 21°C and 34°C. In NPs-treated animals, however, attenuation of METH-induced brain pathology occurred only after repeated exposure of H-290/51 (−30 min, 0 min and +30 min). These observations are the first to show that NPs aggravate METH-induced brain pathology in both cold and hot environments and demonstrate that timely intervention with antioxidant H-290/51 could have neuroprotective effects.

Regulation of Inflammatory Cytokines for Spinal Cord Injury Repair Through Local Delivery of Therapeutic Agents

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“…Several investigations have used antibodies to directly inhibit the levels of certain inflammatory cytokines. Local applications of anti‐TNF‐α antibodies reduced apoptosis, and attenuated BSCB disturbances and cord pathology, thus enhancing neurorepair . The suitable combination of antibodies against TNF‐α and NOS also improved neuroprotection and functional recovery .…”

Review of natural antioxidant plants to overcome the neurotoxic effects of methamphetamine

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An insight on chronic unpredictable stress in association with pathophysiology, neurotransmitters, and experimental models

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