Effect of Metformin and Sitagliptin on Doxorubicin-Induced Cardiotoxicity in Rats: Impact of Oxidative Stress, Inflammation, and Apoptosis
Doxorubicin (DOX) is a widely used antineoplastic drug whose efficacy is limited by its cardiotoxicity. The aim of this study was to investigate the possible protective role of the antidiabetic drugs metformin (250 mg/kg dissolved in DW p.o. for seven days) and sitagliptin (10 mg/kg dissolved in DW...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Toxicology |
| Online Access: | http://dx.doi.org/10.1155/2015/424813 |
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| author | Mina Thabet Kelleni Entesar Farghaly Amin Aly Mohamed Abdelrahman |
| author_facet | Mina Thabet Kelleni Entesar Farghaly Amin Aly Mohamed Abdelrahman |
| author_sort | Mina Thabet Kelleni |
| collection | DOAJ |
| description | Doxorubicin (DOX) is a widely used antineoplastic drug whose efficacy is limited by its cardiotoxicity. The aim of this study was to investigate the possible protective role of the antidiabetic drugs metformin (250 mg/kg dissolved in DW p.o. for seven days) and sitagliptin (10 mg/kg dissolved in DW p.o. for seven days) in a model of DOX-induced (single dose 15 mg/kg i.p. at the fifth day) cardiotoxicity in rats. Results of our study revealed that pretreatment with metformin or sitagliptin produced significant (P<0.05) cardiac protection manifested by a significant decrease in serum levels of LDH and CK-MB enzymes and cardiac MDA and total nitrites and nitrates levels, a significant increase in cardiac SOD activity, and remarkable improvement in the histopathological features as well as a significant reduction in the immunohistochemical expression of COX-2, iNOS, and caspase-3 enzymes as compared to DOX group. These results may suggest using metformin and/or sitagliptin as preferable drugs for diabetic patients suffering from cancer and receiving DOX in their chemotherapy regimen. |
| format | Article |
| id | doaj-art-39871572ab17464d9aa88e7b27da2251 |
| institution | Kabale University |
| issn | 1687-8191 1687-8205 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Toxicology |
| spelling | doaj-art-39871572ab17464d9aa88e7b27da22512025-02-03T01:12:52ZengWileyJournal of Toxicology1687-81911687-82052015-01-01201510.1155/2015/424813424813Effect of Metformin and Sitagliptin on Doxorubicin-Induced Cardiotoxicity in Rats: Impact of Oxidative Stress, Inflammation, and ApoptosisMina Thabet Kelleni0Entesar Farghaly Amin1Aly Mohamed Abdelrahman2Department of Pharmacology, Faculty of Medicine, Minia University, Minia, EgyptDepartment of Pharmacology, Faculty of Medicine, Minia University, Minia, EgyptDepartment of Pharmacology, Faculty of Medicine, Minia University, Minia, EgyptDoxorubicin (DOX) is a widely used antineoplastic drug whose efficacy is limited by its cardiotoxicity. The aim of this study was to investigate the possible protective role of the antidiabetic drugs metformin (250 mg/kg dissolved in DW p.o. for seven days) and sitagliptin (10 mg/kg dissolved in DW p.o. for seven days) in a model of DOX-induced (single dose 15 mg/kg i.p. at the fifth day) cardiotoxicity in rats. Results of our study revealed that pretreatment with metformin or sitagliptin produced significant (P<0.05) cardiac protection manifested by a significant decrease in serum levels of LDH and CK-MB enzymes and cardiac MDA and total nitrites and nitrates levels, a significant increase in cardiac SOD activity, and remarkable improvement in the histopathological features as well as a significant reduction in the immunohistochemical expression of COX-2, iNOS, and caspase-3 enzymes as compared to DOX group. These results may suggest using metformin and/or sitagliptin as preferable drugs for diabetic patients suffering from cancer and receiving DOX in their chemotherapy regimen.http://dx.doi.org/10.1155/2015/424813 |
| spellingShingle | Mina Thabet Kelleni Entesar Farghaly Amin Aly Mohamed Abdelrahman Effect of Metformin and Sitagliptin on Doxorubicin-Induced Cardiotoxicity in Rats: Impact of Oxidative Stress, Inflammation, and Apoptosis Journal of Toxicology |
| title | Effect of Metformin and Sitagliptin on Doxorubicin-Induced Cardiotoxicity in Rats: Impact of Oxidative Stress, Inflammation, and Apoptosis |
| title_full | Effect of Metformin and Sitagliptin on Doxorubicin-Induced Cardiotoxicity in Rats: Impact of Oxidative Stress, Inflammation, and Apoptosis |
| title_fullStr | Effect of Metformin and Sitagliptin on Doxorubicin-Induced Cardiotoxicity in Rats: Impact of Oxidative Stress, Inflammation, and Apoptosis |
| title_full_unstemmed | Effect of Metformin and Sitagliptin on Doxorubicin-Induced Cardiotoxicity in Rats: Impact of Oxidative Stress, Inflammation, and Apoptosis |
| title_short | Effect of Metformin and Sitagliptin on Doxorubicin-Induced Cardiotoxicity in Rats: Impact of Oxidative Stress, Inflammation, and Apoptosis |
| title_sort | effect of metformin and sitagliptin on doxorubicin induced cardiotoxicity in rats impact of oxidative stress inflammation and apoptosis |
| url | http://dx.doi.org/10.1155/2015/424813 |
| work_keys_str_mv | AT minathabetkelleni effectofmetforminandsitagliptinondoxorubicininducedcardiotoxicityinratsimpactofoxidativestressinflammationandapoptosis AT entesarfarghalyamin effectofmetforminandsitagliptinondoxorubicininducedcardiotoxicityinratsimpactofoxidativestressinflammationandapoptosis AT alymohamedabdelrahman effectofmetforminandsitagliptinondoxorubicininducedcardiotoxicityinratsimpactofoxidativestressinflammationandapoptosis |