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Asiatic acid protects against cognitive deficits and reductions in cell proliferation and survival in the rat hippocampus caused by 5-fluorouracil chemotherapy

The chemotherapy drug, 5-fluorouracil (5-FU), has been reported to cause cognitive impairments in cancer patients. The drug also reduces cell proliferation and survival in the brain. Asiatic acid (AA) is a triterpene compound found in Centella asiatica that can protect against reduction of neurogene...

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Autores principales: Chaisawang, Pornthip, Sirichoat, Apiwat, Chaijaroonkhanarak, Wunnee, Pannangrong, Wanassanun, Sripanidkulchai, Bungorn, Wigmore, Peter, Welbat, Jariya Umka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503269/
https://www.ncbi.nlm.nih.gov/pubmed/28700628
http://dx.doi.org/10.1371/journal.pone.0180650
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author Chaisawang, Pornthip
Sirichoat, Apiwat
Chaijaroonkhanarak, Wunnee
Pannangrong, Wanassanun
Sripanidkulchai, Bungorn
Wigmore, Peter
Welbat, Jariya Umka
author_facet Chaisawang, Pornthip
Sirichoat, Apiwat
Chaijaroonkhanarak, Wunnee
Pannangrong, Wanassanun
Sripanidkulchai, Bungorn
Wigmore, Peter
Welbat, Jariya Umka
author_sort Chaisawang, Pornthip
collection PubMed
description The chemotherapy drug, 5-fluorouracil (5-FU), has been reported to cause cognitive impairments in cancer patients. The drug also reduces cell proliferation and survival in the brain. Asiatic acid (AA) is a triterpene compound found in Centella asiatica that can protect against reduction of neurogenesis in the hippocampus and memory deficits induced by valproic acid (VPA). In the present study, we investigated the preventive effects of AA on the deficits in spatial working memory and cell proliferation and survival caused by 5-FU chemotherapy in a rat model. Male Sprague Dawley rats received 5-FU (5 i.v. injections, 25 mg/kg) on day 8, 11, 14, 17 and 20 of the study. This was co-administered with AA (30 mg/kg, oral gavage tube) either 20 days before receiving 5-FU (preventive), after receiving 5-FU (recovery), or for the entire period of the experiment (throughout). Spatial working memory was determined using the novel object location (NOL) test and hippocampal cell proliferation and survival of dividing cells were quantified using immunohistochemistry. Rats in the 5-FU alone and recovery groups showed memory deficits in the NOL test and reductions in cell proliferation and cell survival in the subgranular zone (SGZ) of the hippocampal dentate gyrus. Rats in the control, AA alone, and both preventive and throughout co-administration groups, however, did not exhibit these characteristics. The results showed that 5-FU chemotherapy impaired memory and reduced cell proliferation and cell survival in the SGZ of the hippocampal dentate gyrus. However, these impairments in the animals receiving 5-FU chemotherapy were restored to control levels when AA was co-administered before and during 5-FU treatment. These data demonstrate that AA can prevent the spatial working memory and hippocampal neurogenesis impairments caused by 5-FU chemotherapy.
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spelling pubmed-55032692017-07-25 Asiatic acid protects against cognitive deficits and reductions in cell proliferation and survival in the rat hippocampus caused by 5-fluorouracil chemotherapy Chaisawang, Pornthip Sirichoat, Apiwat Chaijaroonkhanarak, Wunnee Pannangrong, Wanassanun Sripanidkulchai, Bungorn Wigmore, Peter Welbat, Jariya Umka PLoS One Research Article The chemotherapy drug, 5-fluorouracil (5-FU), has been reported to cause cognitive impairments in cancer patients. The drug also reduces cell proliferation and survival in the brain. Asiatic acid (AA) is a triterpene compound found in Centella asiatica that can protect against reduction of neurogenesis in the hippocampus and memory deficits induced by valproic acid (VPA). In the present study, we investigated the preventive effects of AA on the deficits in spatial working memory and cell proliferation and survival caused by 5-FU chemotherapy in a rat model. Male Sprague Dawley rats received 5-FU (5 i.v. injections, 25 mg/kg) on day 8, 11, 14, 17 and 20 of the study. This was co-administered with AA (30 mg/kg, oral gavage tube) either 20 days before receiving 5-FU (preventive), after receiving 5-FU (recovery), or for the entire period of the experiment (throughout). Spatial working memory was determined using the novel object location (NOL) test and hippocampal cell proliferation and survival of dividing cells were quantified using immunohistochemistry. Rats in the 5-FU alone and recovery groups showed memory deficits in the NOL test and reductions in cell proliferation and cell survival in the subgranular zone (SGZ) of the hippocampal dentate gyrus. Rats in the control, AA alone, and both preventive and throughout co-administration groups, however, did not exhibit these characteristics. The results showed that 5-FU chemotherapy impaired memory and reduced cell proliferation and cell survival in the SGZ of the hippocampal dentate gyrus. However, these impairments in the animals receiving 5-FU chemotherapy were restored to control levels when AA was co-administered before and during 5-FU treatment. These data demonstrate that AA can prevent the spatial working memory and hippocampal neurogenesis impairments caused by 5-FU chemotherapy. Public Library of Science 2017-07-10 /pmc/articles/PMC5503269/ /pubmed/28700628 http://dx.doi.org/10.1371/journal.pone.0180650 Text en © 2017 Chaisawang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Chaisawang, Pornthip
Sirichoat, Apiwat
Chaijaroonkhanarak, Wunnee
Pannangrong, Wanassanun
Sripanidkulchai, Bungorn
Wigmore, Peter
Welbat, Jariya Umka
Asiatic acid protects against cognitive deficits and reductions in cell proliferation and survival in the rat hippocampus caused by 5-fluorouracil chemotherapy
title Asiatic acid protects against cognitive deficits and reductions in cell proliferation and survival in the rat hippocampus caused by 5-fluorouracil chemotherapy
title_full Asiatic acid protects against cognitive deficits and reductions in cell proliferation and survival in the rat hippocampus caused by 5-fluorouracil chemotherapy
title_fullStr Asiatic acid protects against cognitive deficits and reductions in cell proliferation and survival in the rat hippocampus caused by 5-fluorouracil chemotherapy
title_full_unstemmed Asiatic acid protects against cognitive deficits and reductions in cell proliferation and survival in the rat hippocampus caused by 5-fluorouracil chemotherapy
title_short Asiatic acid protects against cognitive deficits and reductions in cell proliferation and survival in the rat hippocampus caused by 5-fluorouracil chemotherapy
title_sort asiatic acid protects against cognitive deficits and reductions in cell proliferation and survival in the rat hippocampus caused by 5-fluorouracil chemotherapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503269/
https://www.ncbi.nlm.nih.gov/pubmed/28700628
http://dx.doi.org/10.1371/journal.pone.0180650
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