Cargando…

Mechanisms of Thymoquinone Hepatorenal Protection in Methotrexate-Induced Toxicity in Rats

To investigate mechanisms by which thymoquinone (TQ) can prevent methotrexate- (MTX-) induced hepatorenal toxicity, TQ (10 mg/kg) was administered orally for 10 days. In independent rat groups, MTX hepatorenal toxicity was induced via 20 mg/kg i.p. at the end of day 3 of experiment, with or without...

Descripción completa

Detalles Bibliográficos
Autores principales: El-Sheikh, Azza A. K., Morsy, Mohamed A., Abdalla, Ahlam M., Hamouda, Azza H., Alhaider, Ibrahim A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455533/
https://www.ncbi.nlm.nih.gov/pubmed/26089605
http://dx.doi.org/10.1155/2015/859383
_version_ 1782374750579851264
author El-Sheikh, Azza A. K.
Morsy, Mohamed A.
Abdalla, Ahlam M.
Hamouda, Azza H.
Alhaider, Ibrahim A.
author_facet El-Sheikh, Azza A. K.
Morsy, Mohamed A.
Abdalla, Ahlam M.
Hamouda, Azza H.
Alhaider, Ibrahim A.
author_sort El-Sheikh, Azza A. K.
collection PubMed
description To investigate mechanisms by which thymoquinone (TQ) can prevent methotrexate- (MTX-) induced hepatorenal toxicity, TQ (10 mg/kg) was administered orally for 10 days. In independent rat groups, MTX hepatorenal toxicity was induced via 20 mg/kg i.p. at the end of day 3 of experiment, with or without TQ. MTX caused deterioration in kidney and liver function, namely, blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase. MTX also caused distortion in renal and hepatic histology, with significant oxidative stress, manifested by decrease in reduced glutathione and catalase, as well as increase in malondialdehyde levels. In addition, MTX caused nitrosative stress manifested by increased nitric oxide, with upregulation of inducible nitric oxide synthase. Furthermore, MTX caused hepatorenal inflammatory effects as shown by increased tumor necrosis factor-α, besides upregulation of necrosis factor-κB and cyclooxygenase-2 expressions. MTX also caused apoptotic effect, as it upregulated caspase 3 in liver and kidney. Using TQ concurrently with MTX restored kidney and liver functions, as well as their normal histology. TQ also reversed oxidative and nitrosative stress, as well as inflammatory and apoptotic signs caused by MTX alone. Thus, TQ may be beneficial adjuvant that confers hepatorenal protection to MTX toxicity via antioxidant, antinitrosative, anti-inflammatory, and antiapoptotic mechanisms.
format Online
Article
Text
id pubmed-4455533
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Hindawi Publishing Corporation
record_format MEDLINE/PubMed
spelling pubmed-44555332015-06-18 Mechanisms of Thymoquinone Hepatorenal Protection in Methotrexate-Induced Toxicity in Rats El-Sheikh, Azza A. K. Morsy, Mohamed A. Abdalla, Ahlam M. Hamouda, Azza H. Alhaider, Ibrahim A. Mediators Inflamm Research Article To investigate mechanisms by which thymoquinone (TQ) can prevent methotrexate- (MTX-) induced hepatorenal toxicity, TQ (10 mg/kg) was administered orally for 10 days. In independent rat groups, MTX hepatorenal toxicity was induced via 20 mg/kg i.p. at the end of day 3 of experiment, with or without TQ. MTX caused deterioration in kidney and liver function, namely, blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase. MTX also caused distortion in renal and hepatic histology, with significant oxidative stress, manifested by decrease in reduced glutathione and catalase, as well as increase in malondialdehyde levels. In addition, MTX caused nitrosative stress manifested by increased nitric oxide, with upregulation of inducible nitric oxide synthase. Furthermore, MTX caused hepatorenal inflammatory effects as shown by increased tumor necrosis factor-α, besides upregulation of necrosis factor-κB and cyclooxygenase-2 expressions. MTX also caused apoptotic effect, as it upregulated caspase 3 in liver and kidney. Using TQ concurrently with MTX restored kidney and liver functions, as well as their normal histology. TQ also reversed oxidative and nitrosative stress, as well as inflammatory and apoptotic signs caused by MTX alone. Thus, TQ may be beneficial adjuvant that confers hepatorenal protection to MTX toxicity via antioxidant, antinitrosative, anti-inflammatory, and antiapoptotic mechanisms. Hindawi Publishing Corporation 2015 2015-05-21 /pmc/articles/PMC4455533/ /pubmed/26089605 http://dx.doi.org/10.1155/2015/859383 Text en Copyright © 2015 Azza A. K. El-Sheikh et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
El-Sheikh, Azza A. K.
Morsy, Mohamed A.
Abdalla, Ahlam M.
Hamouda, Azza H.
Alhaider, Ibrahim A.
Mechanisms of Thymoquinone Hepatorenal Protection in Methotrexate-Induced Toxicity in Rats
title Mechanisms of Thymoquinone Hepatorenal Protection in Methotrexate-Induced Toxicity in Rats
title_full Mechanisms of Thymoquinone Hepatorenal Protection in Methotrexate-Induced Toxicity in Rats
title_fullStr Mechanisms of Thymoquinone Hepatorenal Protection in Methotrexate-Induced Toxicity in Rats
title_full_unstemmed Mechanisms of Thymoquinone Hepatorenal Protection in Methotrexate-Induced Toxicity in Rats
title_short Mechanisms of Thymoquinone Hepatorenal Protection in Methotrexate-Induced Toxicity in Rats
title_sort mechanisms of thymoquinone hepatorenal protection in methotrexate-induced toxicity in rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4455533/
https://www.ncbi.nlm.nih.gov/pubmed/26089605
http://dx.doi.org/10.1155/2015/859383
work_keys_str_mv AT elsheikhazzaak mechanismsofthymoquinonehepatorenalprotectioninmethotrexateinducedtoxicityinrats
AT morsymohameda mechanismsofthymoquinonehepatorenalprotectioninmethotrexateinducedtoxicityinrats
AT abdallaahlamm mechanismsofthymoquinonehepatorenalprotectioninmethotrexateinducedtoxicityinrats
AT hamoudaazzah mechanismsofthymoquinonehepatorenalprotectioninmethotrexateinducedtoxicityinrats
AT alhaideribrahima mechanismsofthymoquinonehepatorenalprotectioninmethotrexateinducedtoxicityinrats