Melatonin protects against methotrexate-induced memory deficit and hippocampal neurogenesis impairment in a rat model.


:Methotrexate (MTX) is a chemotherapy agent linked to cognitive deficits in cancer patients received chemotherapy treatment. MTX decreases cell proliferation in the hippocampus, which is concomitant with cognitive deficits in animal models. The present study aimed to investigate the disadvantages of MTX on cognition associated with cell division, survival, and immature neurons involved in hippocampal neurogenesis, as well as the practical neuroprotective effects of melatonin. Male Sprague Dawley rats were given two injections of MTX (75 mg/kg) on days 8 and 15 followed by Leucovorin (LCV, 6 mg/kg) at hours 18, 26, 42, 50 via i.p. injection. Some rats received co-treatment with melatonin (8 mg/kg, i.p. injection) for 15 days before and during MTX administration (preventive), 15 days after MTX administration (recovery), or both (30 days total; throughout). Hippocampal-dependent memory was examined using novel objection location (NOL) and novel object recognition (NOR) tests. Cell division, survival and immature neurons in the subgranular zone (SGZ) in the hippocampus were evaluated using immunofluorescence staining. Rats given MTX/LCV were found to have cognitive memory deterioration based on the NOL and NOR tests. Moreover, reductions in cell division, cell survival, and the numbers of immature neurons were detected in the MTX/LCV group when compared to the controls. This damage was not observed in rats in the preventive, recovery, or throughout groups. These findings reveal that melatonin has the potential to diminish the negative effects of MTX on memory and neurogenesis. This also indicates the benefit of melatonin co-administration in patients who undergo chemotherapy treatment.


Biochem Pharmacol


Biochemical pharmacology


Sirichoat A,Krutsri S,Suwannakot K,Aranarochana A,Chaisawang P,Pannangrong W,Wigmore P,Welbat JU




Has Abstract


2019-05-01 00:00:00












  • Mechanism of inhibition of hepatic bile acid uptake by amiloride and 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS).

    abstract::The mechanisms by which amiloride and 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS) inhibit hepatic uptake of cholate and taurocholate (TC) were investigated in isolated rat hepatocytes. Amiloride inhibited Na(+)-dependent uptake of cholate and TC only when hepatocytes were preincubated with amiloride, indicatin...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Anwer MS,Branson AU,Atkinson JM

    更新日期:1991-12-11 00:00:00

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    更新日期:1995-10-26 00:00:00

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    更新日期:2019-08-01 00:00:00

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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    更新日期:1983-07-01 00:00:00

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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    更新日期:1993-10-19 00:00:00

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    更新日期:1994-04-20 00:00:00

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    更新日期:1984-11-01 00:00:00

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    更新日期:1990-12-01 00:00:00

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Dance AM,Ralton L,Fuller Z,Milne L,Duthie S,Bestwick CS,Lin PK

    更新日期:2005-01-01 00:00:00

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    abstract::Cystic fibrosis (CF) is a common lethal genetic disease caused by autosomal recessive mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel that belongs to the ATP-Binding Cassette (ABC) family of transporters. The class III CF mutations G551D and G1349D are located within the "s...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Melin P,Thoreau V,Norez C,Bilan F,Kitzis A,Becq F

    更新日期:2004-06-15 00:00:00

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: André E,Campi B,Trevisani M,Ferreira J,Malheiros A,Yunes RA,Calixto JB,Geppetti P

    更新日期:2006-04-14 00:00:00

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Yu SP

    更新日期:2003-10-15 00:00:00

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


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    更新日期:2012-12-15 00:00:00

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: McKenna JP,Hanson PJ

    更新日期:1993-08-17 00:00:00

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    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Testa B

    更新日期:2004-12-01 00:00:00