Protective Effects of Thymoquinone against Methotrexate-Induced Germ Cell Apoptosis in Male Mice

Background Toxic effects of anti-cancer and other drugs on the normal tissues could be reduced by the herbal plants and their fractions. This study investigated the protective effect of thymoquinone (TQ) as a fraction of Nigella sativa on methotrexate (MTX)- induced germ cell apoptosis in male mice....

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Main Authors: Fatemeh Sheikhbahaei, Mozafar Khazaei, Arezou Rabzia, Kamran Mansouri, Ali Ghanbari
Format: Article
Language:English
Published: Royan Institute (ACECR), Tehran 2016-01-01
Series:International Journal of Fertility and Sterility
Subjects:
Online Access:http://www.ijfs.ir/article_45347_1402297bf767a09879c6f360e456b36a.pdf
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author Fatemeh Sheikhbahaei
Mozafar Khazaei
Arezou Rabzia
Kamran Mansouri
Ali Ghanbari
author_facet Fatemeh Sheikhbahaei
Mozafar Khazaei
Arezou Rabzia
Kamran Mansouri
Ali Ghanbari
author_sort Fatemeh Sheikhbahaei
collection DOAJ
description Background Toxic effects of anti-cancer and other drugs on the normal tissues could be reduced by the herbal plants and their fractions. This study investigated the protective effect of thymoquinone (TQ) as a fraction of Nigella sativa on methotrexate (MTX)- induced germ cell apoptosis in male mice. Materials and Methods In this experimental study, thirty male Balb/c mice were divided randomly into 5 groups (n=6). A single dose of MTX (20 mg/kg) and different concentrations of TQ were administrated for 4 consecutive days. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed on paraffin embedded tissue sections to analysis the occurrence of apoptosis in the testis. Reverse transcription polymerase chain reaction (RT-PCR) of apoptosis-related genes was performed with RNA extracted from testes of the mice. Statistical analysis was done using one-way ANOVA. Results In the MTX group, there was a significant increase in morphologic sign of germ cell degeneration of tubules (48 ± 0.6%), apoptotic index (AI; 2.3 ± 0.6%), as well as mRNA expression of p53 (P=0.008), caspase 8 (P=0.002), caspase 3 (P=0.005), caspase 9 (P=0.000), bax (P=0.004) and the ratio of bax/bcl-2 (P=0.000), whereas there was an decrease in the expression of bcl-2 (P=0.003), as compared to control group. In MTX+TQ groups, the data showed that different concentrations of TQ could improve the harmful effects caused by the MTX. The best protective effects were achieved in MTX+TQ (10 mg/kg). Conclusion TQ protects testicular germ cell against MTX-induced apoptosis by affecting related genes regulation.
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spelling doaj.art-7b9056428a384782bdeeb328156f9f612022-12-21T17:58:34ZengRoyan Institute (ACECR), TehranInternational Journal of Fertility and Sterility2008-076X2008-07782016-01-019454154710.22074/ijfs.2016.461445347Protective Effects of Thymoquinone against Methotrexate-Induced Germ Cell Apoptosis in Male MiceFatemeh Sheikhbahaei0Mozafar Khazaei1Arezou Rabzia2Kamran Mansouri3Ali Ghanbari4Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, IranFertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, IranFertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, IranMedical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, IranFertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, IranBackground Toxic effects of anti-cancer and other drugs on the normal tissues could be reduced by the herbal plants and their fractions. This study investigated the protective effect of thymoquinone (TQ) as a fraction of Nigella sativa on methotrexate (MTX)- induced germ cell apoptosis in male mice. Materials and Methods In this experimental study, thirty male Balb/c mice were divided randomly into 5 groups (n=6). A single dose of MTX (20 mg/kg) and different concentrations of TQ were administrated for 4 consecutive days. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed on paraffin embedded tissue sections to analysis the occurrence of apoptosis in the testis. Reverse transcription polymerase chain reaction (RT-PCR) of apoptosis-related genes was performed with RNA extracted from testes of the mice. Statistical analysis was done using one-way ANOVA. Results In the MTX group, there was a significant increase in morphologic sign of germ cell degeneration of tubules (48 ± 0.6%), apoptotic index (AI; 2.3 ± 0.6%), as well as mRNA expression of p53 (P=0.008), caspase 8 (P=0.002), caspase 3 (P=0.005), caspase 9 (P=0.000), bax (P=0.004) and the ratio of bax/bcl-2 (P=0.000), whereas there was an decrease in the expression of bcl-2 (P=0.003), as compared to control group. In MTX+TQ groups, the data showed that different concentrations of TQ could improve the harmful effects caused by the MTX. The best protective effects were achieved in MTX+TQ (10 mg/kg). Conclusion TQ protects testicular germ cell against MTX-induced apoptosis by affecting related genes regulation.http://www.ijfs.ir/article_45347_1402297bf767a09879c6f360e456b36a.pdfapoptosismethotrexatethymoquinonemicegerm cells
spellingShingle Fatemeh Sheikhbahaei
Mozafar Khazaei
Arezou Rabzia
Kamran Mansouri
Ali Ghanbari
Protective Effects of Thymoquinone against Methotrexate-Induced Germ Cell Apoptosis in Male Mice
International Journal of Fertility and Sterility
apoptosis
methotrexate
thymoquinone
mice
germ cells
title Protective Effects of Thymoquinone against Methotrexate-Induced Germ Cell Apoptosis in Male Mice
title_full Protective Effects of Thymoquinone against Methotrexate-Induced Germ Cell Apoptosis in Male Mice
title_fullStr Protective Effects of Thymoquinone against Methotrexate-Induced Germ Cell Apoptosis in Male Mice
title_full_unstemmed Protective Effects of Thymoquinone against Methotrexate-Induced Germ Cell Apoptosis in Male Mice
title_short Protective Effects of Thymoquinone against Methotrexate-Induced Germ Cell Apoptosis in Male Mice
title_sort protective effects of thymoquinone against methotrexate induced germ cell apoptosis in male mice
topic apoptosis
methotrexate
thymoquinone
mice
germ cells
url http://www.ijfs.ir/article_45347_1402297bf767a09879c6f360e456b36a.pdf
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AT arezourabzia protectiveeffectsofthymoquinoneagainstmethotrexateinducedgermcellapoptosisinmalemice
AT kamranmansouri protectiveeffectsofthymoquinoneagainstmethotrexateinducedgermcellapoptosisinmalemice
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