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Rifampicin attenuates the MPTP-induced neurotoxicity in mouse brain.
Brain Res. 2006 Apr 12; 1082(1):196-204.BR

Abstract

Rifampicin, an antibacterial drug, is highly effective in the treatment of tuberculosis and leprosy. Recently, it has been reported to have neuroprotective effects in in vitro and in vivo models. This study was designed to elucidate its neuroprotective effects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity (known as an in vivo mouse model of Parkinson's disease). Mice were injected intraperitoneally (i.p.) with MPTP (10 mg/kg) four times at 1-h intervals, and brains were analyzed 3 or 7 days later. Rifampicin at 20 mg/kg (i.p., twice) had protective effects against MPTP-induced neuronal damage (immunohistochemical changes in tyrosine hydroxylase) in both the substantia nigra and striatum. Rifampicin also protected against the MPTP-induced depletions of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum. The maximal concentrations of rifampicin between 30 and 240 min after a single rifampicin injection (20 mg/kg, i.p.) were 2.6 microM (at 30 min) in plasma and 0.77 microM (at 60 min) in striatum. Next, the effects of rifampicin on oxidative stress [lipid peroxidation in mouse brain homogenates and free radical-scavenging activity against diphenyl-p-picrylhydrazyl (DPPH)] were evaluated to clarify the underlying mechanism. At 1 microM or more, rifampicin significantly inhibited both lipid peroxidation in the striatum and free radical production. These findings suggest that in mice, rifampicin can reach brain tissues at concentrations sufficient to attenuate MPTP-induced neurodegeneration in the nigrostriatal dopaminergic neuronal pathway, and that an inhibitory effect against oxidative stress may be partly responsible for its observed neuroprotective effects.

Authors+Show Affiliations

Department of Biofunctional Molecules, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

16515773

Citation

Oida, Y, et al. "Rifampicin Attenuates the MPTP-induced Neurotoxicity in Mouse Brain." Brain Research, vol. 1082, no. 1, 2006, pp. 196-204.
Oida Y, Kitaichi K, Nakayama H, et al. Rifampicin attenuates the MPTP-induced neurotoxicity in mouse brain. Brain Res. 2006;1082(1):196-204.
Oida, Y., Kitaichi, K., Nakayama, H., Ito, Y., Fujimoto, Y., Shimazawa, M., Nagai, H., & Hara, H. (2006). Rifampicin attenuates the MPTP-induced neurotoxicity in mouse brain. Brain Research, 1082(1), 196-204.
Oida Y, et al. Rifampicin Attenuates the MPTP-induced Neurotoxicity in Mouse Brain. Brain Res. 2006 Apr 12;1082(1):196-204. PubMed PMID: 16515773.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rifampicin attenuates the MPTP-induced neurotoxicity in mouse brain. AU - Oida,Y, AU - Kitaichi,K, AU - Nakayama,H, AU - Ito,Y, AU - Fujimoto,Y, AU - Shimazawa,M, AU - Nagai,H, AU - Hara,H, Y1 - 2006/03/03/ PY - 2005/11/16/received PY - 2006/01/25/revised PY - 2006/01/28/accepted PY - 2006/3/7/pubmed PY - 2006/7/14/medline PY - 2006/3/7/entrez SP - 196 EP - 204 JF - Brain research JO - Brain Res VL - 1082 IS - 1 N2 - Rifampicin, an antibacterial drug, is highly effective in the treatment of tuberculosis and leprosy. Recently, it has been reported to have neuroprotective effects in in vitro and in vivo models. This study was designed to elucidate its neuroprotective effects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity (known as an in vivo mouse model of Parkinson's disease). Mice were injected intraperitoneally (i.p.) with MPTP (10 mg/kg) four times at 1-h intervals, and brains were analyzed 3 or 7 days later. Rifampicin at 20 mg/kg (i.p., twice) had protective effects against MPTP-induced neuronal damage (immunohistochemical changes in tyrosine hydroxylase) in both the substantia nigra and striatum. Rifampicin also protected against the MPTP-induced depletions of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum. The maximal concentrations of rifampicin between 30 and 240 min after a single rifampicin injection (20 mg/kg, i.p.) were 2.6 microM (at 30 min) in plasma and 0.77 microM (at 60 min) in striatum. Next, the effects of rifampicin on oxidative stress [lipid peroxidation in mouse brain homogenates and free radical-scavenging activity against diphenyl-p-picrylhydrazyl (DPPH)] were evaluated to clarify the underlying mechanism. At 1 microM or more, rifampicin significantly inhibited both lipid peroxidation in the striatum and free radical production. These findings suggest that in mice, rifampicin can reach brain tissues at concentrations sufficient to attenuate MPTP-induced neurodegeneration in the nigrostriatal dopaminergic neuronal pathway, and that an inhibitory effect against oxidative stress may be partly responsible for its observed neuroprotective effects. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/16515773/Rifampicin_attenuates_the_MPTP_induced_neurotoxicity_in_mouse_brain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(06)00313-1 DB - PRIME DP - Unbound Medicine ER -