Effect of the combination of metformin hydrochloride and melatonin on oxidative stress before and during pregnancy, and biochemical and histopathological analysis of the livers of rats after treatment for polycystic ovary syndrome
The aim of the present study was to analyze the effect of a combination of metformin hydrochloride and melatonin on oxidative stress together with a biochemical and histopathological analysis of the livers of Wistar rats induced with PCOS. The results indicated that a combination of the drugs was mo...
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creator | Lemos, Ana Janaina Jeanine M. Peixoto, Christina A. Teixeira, Álvaro Aguiar C. Luna, Rayana Leal A. Rocha, Sura Wanessa S. Santos, Hilda Michelly P. Silva, Amanda Karolina S. Nunes, Ana Karolina S. Wanderley-Teixeira, Valéria |
description | The aim of the present study was to analyze the effect of a combination of metformin hydrochloride and melatonin on oxidative stress together with a biochemical and histopathological analysis of the livers of Wistar rats induced with PCOS. The results indicated that a combination of the drugs was more effective in the reduction of plasmatic levels of liver enzyme alanine aminotransferase, nitric oxide and total glutathione, and decreased the inflammatory response and histopathological damage, producing results that were significantly similar to animals from the control group. A mixture of the drugs produced more effective results against liver toxicity caused by PCOS, encouraging the normalization of biochemical parameters. During pregnancy, there was reduced oxidative stress compared to monotherapeutic use of these drugs. Interestingly, the combination of the drugs caused a physiological reaction similar to responses identified in healthy rats without induction of the PCOS control group. However, the clinical and physiological effectiveness of the combination should be further explored, especially with respect to the possible side effects on offspring.
[Display omitted]
•Studies have documented increased oxidative stress in patients with PCOS.•It has been noted that women with PCOS have a high prevalence of liver alterations.•Liver disease in pregnancy may be pre-existing increasing the newborn mortality.•Metformin/melatonin associated reduced oxidative stress in liver in pregnant rats.•Association of metformin/melatonin normalizes hepatic biochemical parameters. |
doi_str_mv | 10.1016/j.taap.2014.05.015 |
format | Article |
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[Display omitted]
•Studies have documented increased oxidative stress in patients with PCOS.•It has been noted that women with PCOS have a high prevalence of liver alterations.•Liver disease in pregnancy may be pre-existing increasing the newborn mortality.•Metformin/melatonin associated reduced oxidative stress in liver in pregnant rats.•Association of metformin/melatonin normalizes hepatic biochemical parameters.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2014.05.015</identifier><identifier>PMID: 24918699</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; ALANINES ; Animals ; Antioxidants - administration & dosage ; DISEASES ; Drug Therapy, Combination ; Female ; GLUTATHIONE ; INFLAMMATION ; LIVER ; Liver - drug effects ; Liver - metabolism ; Liver - pathology ; MELATONIN ; Melatonin - administration & dosage ; Metformin - administration & dosage ; Metformin hydrochloride ; MORTALITY ; NEONATES ; OVARIES ; OXIDATION ; Oxidative Stress - drug effects ; Oxidative Stress - physiology ; Polycystic ovary syndrome ; Polycystic Ovary Syndrome - drug therapy ; Polycystic Ovary Syndrome - metabolism ; Polycystic Ovary Syndrome - pathology ; PREGNANCY ; PROGENY ; RATS ; Rats, Wistar ; SIDE EFFECTS ; STRESSES ; TOXICITY ; Treatment Outcome ; WOMEN</subject><ispartof>Toxicology and applied pharmacology, 2014-10, Vol.280 (1), p.159-168</ispartof><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-6dc6e90ba4f0b37315383a2ac92b5e4f1f3d93a39d3af356c90ee9d6661909a23</citedby><cites>FETCH-LOGICAL-c384t-6dc6e90ba4f0b37315383a2ac92b5e4f1f3d93a39d3af356c90ee9d6661909a23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0041008X14002129$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24918699$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22439862$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Lemos, Ana Janaina Jeanine M.</creatorcontrib><creatorcontrib>Peixoto, Christina A.</creatorcontrib><creatorcontrib>Teixeira, Álvaro Aguiar C.</creatorcontrib><creatorcontrib>Luna, Rayana Leal A.</creatorcontrib><creatorcontrib>Rocha, Sura Wanessa S.</creatorcontrib><creatorcontrib>Santos, Hilda Michelly P.</creatorcontrib><creatorcontrib>Silva, Amanda Karolina S.</creatorcontrib><creatorcontrib>Nunes, Ana Karolina S.</creatorcontrib><creatorcontrib>Wanderley-Teixeira, Valéria</creatorcontrib><title>Effect of the combination of metformin hydrochloride and melatonin on oxidative stress before and during pregnancy, and biochemical and histopathological analysis of the livers of rats after treatment for polycystic ovary syndrome</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>The aim of the present study was to analyze the effect of a combination of metformin hydrochloride and melatonin on oxidative stress together with a biochemical and histopathological analysis of the livers of Wistar rats induced with PCOS. The results indicated that a combination of the drugs was more effective in the reduction of plasmatic levels of liver enzyme alanine aminotransferase, nitric oxide and total glutathione, and decreased the inflammatory response and histopathological damage, producing results that were significantly similar to animals from the control group. A mixture of the drugs produced more effective results against liver toxicity caused by PCOS, encouraging the normalization of biochemical parameters. During pregnancy, there was reduced oxidative stress compared to monotherapeutic use of these drugs. Interestingly, the combination of the drugs caused a physiological reaction similar to responses identified in healthy rats without induction of the PCOS control group. However, the clinical and physiological effectiveness of the combination should be further explored, especially with respect to the possible side effects on offspring.
[Display omitted]
•Studies have documented increased oxidative stress in patients with PCOS.•It has been noted that women with PCOS have a high prevalence of liver alterations.•Liver disease in pregnancy may be pre-existing increasing the newborn mortality.•Metformin/melatonin associated reduced oxidative stress in liver in pregnant rats.•Association of metformin/melatonin normalizes hepatic biochemical parameters.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>ALANINES</subject><subject>Animals</subject><subject>Antioxidants - administration & dosage</subject><subject>DISEASES</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>GLUTATHIONE</subject><subject>INFLAMMATION</subject><subject>LIVER</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>MELATONIN</subject><subject>Melatonin - administration & dosage</subject><subject>Metformin - administration & dosage</subject><subject>Metformin hydrochloride</subject><subject>MORTALITY</subject><subject>NEONATES</subject><subject>OVARIES</subject><subject>OXIDATION</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxidative Stress - physiology</subject><subject>Polycystic ovary syndrome</subject><subject>Polycystic Ovary Syndrome - drug therapy</subject><subject>Polycystic Ovary Syndrome - metabolism</subject><subject>Polycystic Ovary Syndrome - pathology</subject><subject>PREGNANCY</subject><subject>PROGENY</subject><subject>RATS</subject><subject>Rats, Wistar</subject><subject>SIDE EFFECTS</subject><subject>STRESSES</subject><subject>TOXICITY</subject><subject>Treatment Outcome</subject><subject>WOMEN</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uc2O1SAUJkbjXEdfwIUhcWsrlBZL4sZMxp9kEjeauCMUDrfctNAAc2Nf2OeQ3s64dEU45_uDD6HXlNSUUP7-VGellrohtK1JVxPaPUEHSgSvCGPsKToQ0tKKkP7XFXqR0okQItqWPkdXTStoz4U4oD-31oLOOFicR8A6zIPzKrvgt9EM2YY4O4_H1cSgxylEZwArb8puUjn4stuwv50prDPglCOkhAcoxB1o7qPzR7xEOHrl9fruMh1ckYPZaTVd7qNLOSwqj2EKx4epmtbk0mO2qcjHyy2qnLCyGSIubirP4DMufngJ06rXlJ3G4aziitPqS-4ZXqJnVk0JXj2c1-jn59sfN1-ru-9fvt18uqs069tccaM5CDKo1pKBfWC0Yz1TjdKiGTpoLbXMCKaYMExZ1nEtCIAwnHMqiFANu0Zvd91QQsikXQY96uB9-WPZNC0TPd9QzY7SMaQUwcolurnklZTIrVp5klu1cqtWkk6WagvpzU5a7ocZzD_KY5cF8HEHQHng2UHc_MFrMC5u9ia4_-n_Be9NvJw</recordid><startdate>20141001</startdate><enddate>20141001</enddate><creator>Lemos, Ana Janaina Jeanine M.</creator><creator>Peixoto, Christina A.</creator><creator>Teixeira, Álvaro Aguiar C.</creator><creator>Luna, Rayana Leal A.</creator><creator>Rocha, Sura Wanessa S.</creator><creator>Santos, Hilda Michelly P.</creator><creator>Silva, Amanda Karolina S.</creator><creator>Nunes, Ana Karolina S.</creator><creator>Wanderley-Teixeira, Valéria</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>OTOTI</scope></search><sort><creationdate>20141001</creationdate><title>Effect of the combination of metformin hydrochloride and melatonin on oxidative stress before and during pregnancy, and biochemical and histopathological analysis of the livers of rats after treatment for polycystic ovary syndrome</title><author>Lemos, Ana Janaina Jeanine M. ; Peixoto, Christina A. ; Teixeira, Álvaro Aguiar C. ; Luna, Rayana Leal A. ; Rocha, Sura Wanessa S. ; Santos, Hilda Michelly P. ; Silva, Amanda Karolina S. ; Nunes, Ana Karolina S. ; Wanderley-Teixeira, Valéria</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-6dc6e90ba4f0b37315383a2ac92b5e4f1f3d93a39d3af356c90ee9d6661909a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>ALANINES</topic><topic>Animals</topic><topic>Antioxidants - administration & dosage</topic><topic>DISEASES</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>GLUTATHIONE</topic><topic>INFLAMMATION</topic><topic>LIVER</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>MELATONIN</topic><topic>Melatonin - administration & dosage</topic><topic>Metformin - administration & dosage</topic><topic>Metformin hydrochloride</topic><topic>MORTALITY</topic><topic>NEONATES</topic><topic>OVARIES</topic><topic>OXIDATION</topic><topic>Oxidative Stress - drug effects</topic><topic>Oxidative Stress - physiology</topic><topic>Polycystic ovary syndrome</topic><topic>Polycystic Ovary Syndrome - drug therapy</topic><topic>Polycystic Ovary Syndrome - metabolism</topic><topic>Polycystic Ovary Syndrome - pathology</topic><topic>PREGNANCY</topic><topic>PROGENY</topic><topic>RATS</topic><topic>Rats, Wistar</topic><topic>SIDE EFFECTS</topic><topic>STRESSES</topic><topic>TOXICITY</topic><topic>Treatment Outcome</topic><topic>WOMEN</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lemos, Ana Janaina Jeanine M.</creatorcontrib><creatorcontrib>Peixoto, Christina A.</creatorcontrib><creatorcontrib>Teixeira, Álvaro Aguiar C.</creatorcontrib><creatorcontrib>Luna, Rayana Leal A.</creatorcontrib><creatorcontrib>Rocha, Sura Wanessa S.</creatorcontrib><creatorcontrib>Santos, Hilda Michelly P.</creatorcontrib><creatorcontrib>Silva, Amanda Karolina S.</creatorcontrib><creatorcontrib>Nunes, Ana Karolina S.</creatorcontrib><creatorcontrib>Wanderley-Teixeira, Valéria</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>OSTI.GOV</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lemos, Ana Janaina Jeanine M.</au><au>Peixoto, Christina A.</au><au>Teixeira, Álvaro Aguiar C.</au><au>Luna, Rayana Leal A.</au><au>Rocha, Sura Wanessa S.</au><au>Santos, Hilda Michelly P.</au><au>Silva, Amanda Karolina S.</au><au>Nunes, Ana Karolina S.</au><au>Wanderley-Teixeira, Valéria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of the combination of metformin hydrochloride and melatonin on oxidative stress before and during pregnancy, and biochemical and histopathological analysis of the livers of rats after treatment for polycystic ovary syndrome</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2014-10-01</date><risdate>2014</risdate><volume>280</volume><issue>1</issue><spage>159</spage><epage>168</epage><pages>159-168</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><abstract>The aim of the present study was to analyze the effect of a combination of metformin hydrochloride and melatonin on oxidative stress together with a biochemical and histopathological analysis of the livers of Wistar rats induced with PCOS. The results indicated that a combination of the drugs was more effective in the reduction of plasmatic levels of liver enzyme alanine aminotransferase, nitric oxide and total glutathione, and decreased the inflammatory response and histopathological damage, producing results that were significantly similar to animals from the control group. A mixture of the drugs produced more effective results against liver toxicity caused by PCOS, encouraging the normalization of biochemical parameters. During pregnancy, there was reduced oxidative stress compared to monotherapeutic use of these drugs. Interestingly, the combination of the drugs caused a physiological reaction similar to responses identified in healthy rats without induction of the PCOS control group. However, the clinical and physiological effectiveness of the combination should be further explored, especially with respect to the possible side effects on offspring.
[Display omitted]
•Studies have documented increased oxidative stress in patients with PCOS.•It has been noted that women with PCOS have a high prevalence of liver alterations.•Liver disease in pregnancy may be pre-existing increasing the newborn mortality.•Metformin/melatonin associated reduced oxidative stress in liver in pregnant rats.•Association of metformin/melatonin normalizes hepatic biochemical parameters.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24918699</pmid><doi>10.1016/j.taap.2014.05.015</doi><tpages>10</tpages></addata></record> |
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subjects | 60 APPLIED LIFE SCIENCES ALANINES Animals Antioxidants - administration & dosage DISEASES Drug Therapy, Combination Female GLUTATHIONE INFLAMMATION LIVER Liver - drug effects Liver - metabolism Liver - pathology MELATONIN Melatonin - administration & dosage Metformin - administration & dosage Metformin hydrochloride MORTALITY NEONATES OVARIES OXIDATION Oxidative Stress - drug effects Oxidative Stress - physiology Polycystic ovary syndrome Polycystic Ovary Syndrome - drug therapy Polycystic Ovary Syndrome - metabolism Polycystic Ovary Syndrome - pathology PREGNANCY PROGENY RATS Rats, Wistar SIDE EFFECTS STRESSES TOXICITY Treatment Outcome WOMEN |
title | Effect of the combination of metformin hydrochloride and melatonin on oxidative stress before and during pregnancy, and biochemical and histopathological analysis of the livers of rats after treatment for polycystic ovary syndrome |
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