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Rutin Supplementation in the Diet has Protective Effects Against Toxicant-Induced Hippocampal Injury by Suppression of Microglial Activation and Pro-Inflammatory Cytokines

Protective Effect of Rutin Against Toxicant-Induced Hippocampal Injury

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Abstract

Aims Rutin is one of the flavonoids that has many beneficial effects on the health. Previously, we showed that rutin has a protective effect on trimethyltin (TMT)-induced memory dysfunction in rats. The aim of this study was to investigate the protective effects of rutin on TMT-induced hippocampal injury and the time course profiles of these effects in rats. Methods Four-week-old male Sprague-Dawley (SD) rats were fed chow with or without rutin (0.75%) during the experimental period and were administered with a single dose of TMT (8.5 mg/kg b.w., p.o.) or vehicle at 6 weeks of age. The rats were sacrificed 5, 10, or 20 days after the TMT administration and then histological and molecular examinations of the hippocampus were performed. Results Rutin supplementation suppressed the TMT-induced decrease in the number of hippocampal pyramidal neurons 20 days after TMT administration. The TMT-induced up-regulation of the mRNA expression levels of reactive microglia marker and pro-inflammatory cytokines were reversed by rutin supplementation 10 or 20 days after the TMT administration. Conclusions These results suggested that the neuroprotective effect of rutin on TMT-induced spatial memory impairment could be attributable to its inhibitory effect against microglial activation and its role in synapse formation via neurotrophic factors in the hippocampus.

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Abbreviations

TMT:

Trimethyltin

SD:

Sprague-Dawley

CA:

Cornu ammonis

GFAP:

Glial fibrillary acidic protein

IL:

Interleukin

TNF:

Tumor necrosis factor

BDNF:

Brain-derived neurotrophic factor

bFGF:

Basic fibroblast growth factor

PCR:

polymerase chain reaction

Ct:

Cycle of threshold

RT:

Reverse transcription

ANOVA:

Analysis of variance

PLSD:

Protected least-squares difference

CNS:

Central nervous system

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Acknowledgment

The authors thank Hirohisa Takano (National Institute for Environmental Studies, Japan) for helpful comment on the design of this study.

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Correspondence to Hideki Imai.

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Koda, T., Kuroda, Y. & Imai, H. Rutin Supplementation in the Diet has Protective Effects Against Toxicant-Induced Hippocampal Injury by Suppression of Microglial Activation and Pro-Inflammatory Cytokines. Cell Mol Neurobiol 29, 523–531 (2009). https://doi.org/10.1007/s10571-008-9344-4

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  • DOI: https://doi.org/10.1007/s10571-008-9344-4

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