Mokko Lactone Attenuates Doxorubicin-Induced Hepatotoxicity in Rats: Emphasis on Sirt-1/FOXO1/NF-κB Axis

Doxorubicin (DOX), a common chemotherapeutic agent, suffers serious adverse effects including hepatotoxicity. Mokko lactone (ML) is a guainolide sesquiterpene with promising biological activities. The study aimed to evaluate the protection offered by ML against hepatotoxicity induced by DOX in rats....

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Autores principales:	Alaa Sirwi, Rasheed A. Shaik, Abdulmohsin J. Alamoudi, Basma G. Eid, Ahmed K. Kammoun, Sabrin R. M. Ibrahim, Gamal A. Mohamed, Hossam M. Abdallah, Ashraf B. Abdel-Naim
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	doxorubicin mokko lactone liver Sirt-1 Nutrition. Foods and food supply TX341-641
Acceso en línea:	https://doaj.org/article/04abce26c7904fd6ac4f97af8bc98c5c
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spelling	oai:doaj.org-article:04abce26c7904fd6ac4f97af8bc98c5c2021-11-25T18:37:05ZMokko Lactone Attenuates Doxorubicin-Induced Hepatotoxicity in Rats: Emphasis on Sirt-1/FOXO1/NF-κB Axis10.3390/nu131141422072-6643https://doaj.org/article/04abce26c7904fd6ac4f97af8bc98c5c2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6643/13/11/4142https://doaj.org/toc/2072-6643Doxorubicin (DOX), a common chemotherapeutic agent, suffers serious adverse effects including hepatotoxicity. Mokko lactone (ML) is a guainolide sesquiterpene with promising biological activities. The study aimed to evaluate the protection offered by ML against hepatotoxicity induced by DOX in rats. Our data indicated ML exhibited protective effects as evidenced by ameliorating the rise in serum activities of alanine transaminase, aspartate transaminase and alkaline phosphatase. This was confirmed histologically as ML prevented DOX-induced pathological alteration in liver architecture. Further, ML administration significantly prevented malondialdehyde accumulation, glutathione depletion and superoxide dismutase and catalase exhaustion. Antioxidant action of ML was associated with enhanced expression of the nuclear translocation of NF-E2-related factor 2 (Nrf2) and a lower expression of forkhead box protein O1 (FOXO1). Also, ML showed potent anti-inflammatory activities highlighted by decreased expression of interleukin 6, tumor necrosis factor α and nuclear factor κB (NF-κB). The anti-apoptotic effects of ML were associated with decreased Bax and enhanced Bcl-2 mRNA expression in liver tissues. ML caused a significant up-regulation in the expression of silent information regulator 1 (Sirt-1). Therefore, it can be concluded that ML prevents liver injury caused by DOX. This could partially be due to the ML regulatory activities on Sirt-1/FOXO1/NF-κB axis.Alaa SirwiRasheed A. ShaikAbdulmohsin J. AlamoudiBasma G. EidAhmed K. KammounSabrin R. M. IbrahimGamal A. MohamedHossam M. AbdallahAshraf B. Abdel-NaimMDPI AGarticledoxorubicinmokko lactoneliverSirt-1Nutrition. Foods and food supplyTX341-641ENNutrients, Vol 13, Iss 4142, p 4142 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	doxorubicin mokko lactone liver Sirt-1 Nutrition. Foods and food supply TX341-641
spellingShingle	doxorubicin mokko lactone liver Sirt-1 Nutrition. Foods and food supply TX341-641 Alaa Sirwi Rasheed A. Shaik Abdulmohsin J. Alamoudi Basma G. Eid Ahmed K. Kammoun Sabrin R. M. Ibrahim Gamal A. Mohamed Hossam M. Abdallah Ashraf B. Abdel-Naim Mokko Lactone Attenuates Doxorubicin-Induced Hepatotoxicity in Rats: Emphasis on Sirt-1/FOXO1/NF-κB Axis
description	Doxorubicin (DOX), a common chemotherapeutic agent, suffers serious adverse effects including hepatotoxicity. Mokko lactone (ML) is a guainolide sesquiterpene with promising biological activities. The study aimed to evaluate the protection offered by ML against hepatotoxicity induced by DOX in rats. Our data indicated ML exhibited protective effects as evidenced by ameliorating the rise in serum activities of alanine transaminase, aspartate transaminase and alkaline phosphatase. This was confirmed histologically as ML prevented DOX-induced pathological alteration in liver architecture. Further, ML administration significantly prevented malondialdehyde accumulation, glutathione depletion and superoxide dismutase and catalase exhaustion. Antioxidant action of ML was associated with enhanced expression of the nuclear translocation of NF-E2-related factor 2 (Nrf2) and a lower expression of forkhead box protein O1 (FOXO1). Also, ML showed potent anti-inflammatory activities highlighted by decreased expression of interleukin 6, tumor necrosis factor α and nuclear factor κB (NF-κB). The anti-apoptotic effects of ML were associated with decreased Bax and enhanced Bcl-2 mRNA expression in liver tissues. ML caused a significant up-regulation in the expression of silent information regulator 1 (Sirt-1). Therefore, it can be concluded that ML prevents liver injury caused by DOX. This could partially be due to the ML regulatory activities on Sirt-1/FOXO1/NF-κB axis.
format	article
author	Alaa Sirwi Rasheed A. Shaik Abdulmohsin J. Alamoudi Basma G. Eid Ahmed K. Kammoun Sabrin R. M. Ibrahim Gamal A. Mohamed Hossam M. Abdallah Ashraf B. Abdel-Naim
author_facet	Alaa Sirwi Rasheed A. Shaik Abdulmohsin J. Alamoudi Basma G. Eid Ahmed K. Kammoun Sabrin R. M. Ibrahim Gamal A. Mohamed Hossam M. Abdallah Ashraf B. Abdel-Naim
author_sort	Alaa Sirwi
title	Mokko Lactone Attenuates Doxorubicin-Induced Hepatotoxicity in Rats: Emphasis on Sirt-1/FOXO1/NF-κB Axis
title_short	Mokko Lactone Attenuates Doxorubicin-Induced Hepatotoxicity in Rats: Emphasis on Sirt-1/FOXO1/NF-κB Axis
title_full	Mokko Lactone Attenuates Doxorubicin-Induced Hepatotoxicity in Rats: Emphasis on Sirt-1/FOXO1/NF-κB Axis
title_fullStr	Mokko Lactone Attenuates Doxorubicin-Induced Hepatotoxicity in Rats: Emphasis on Sirt-1/FOXO1/NF-κB Axis
title_full_unstemmed	Mokko Lactone Attenuates Doxorubicin-Induced Hepatotoxicity in Rats: Emphasis on Sirt-1/FOXO1/NF-κB Axis
title_sort	mokko lactone attenuates doxorubicin-induced hepatotoxicity in rats: emphasis on sirt-1/foxo1/nf-κb axis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/04abce26c7904fd6ac4f97af8bc98c5c
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Mokko Lactone Attenuates Doxorubicin-Induced Hepatotoxicity in Rats: Emphasis on Sirt-1/FOXO1/NF-κB Axis

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