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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Veröffentlicht in:Toxicology and applied pharmacology 2014-10, Vol.280 (1), p.159-168
Hauptverfasser: 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
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container_issue 1
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container_title Toxicology and applied pharmacology
container_volume 280
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
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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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ispartof Toxicology and applied pharmacology, 2014-10, Vol.280 (1), p.159-168
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source ScienceDirect; MEDLINE
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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