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An Electrocardiographic, Molecular and Biochemical Approach to Explore the Cardioprotective Effect of Vasopressin and Milrinone Against Phosphide Toxicity in Rats Publisher Pubmed



Jafari A1, 2, 3, 4 ; Baghaei A1, 2, 3 ; Solgi R1, 2, 3 ; Baeeri M1, 2, 3 ; Chamanara M5 ; Hassani S1, 2, 3 ; Gholami M1, 2, 3 ; Ostad SN1, 2, 3 ; Sharifzadeh M1, 2, 3 ; Abdollahi M1, 2, 3
Authors
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Authors Affiliations
  1. 1. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran, 1417614411, Iran
  2. 2. Pharmaceutical Sciences Research Center, Poisoning and Toxicology Research Center, Tehran, 1417614411, Iran
  3. 3. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, 1417614411, Iran
  4. 4. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
  5. 5. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Food and Chemical Toxicology Published:2015


Abstract

The present study was conducted to identify the protective effect of vasopressin (AVP) and milrinone on cardiovascular function, mitochondrial complex activities, cellular ATP reserve, oxidative stress, and apoptosis in rats poisoned by aluminum phosphide (AlP). Rats were divided into five groups (n = 12) including control, AlP (12.5 mg/kg), AlP + AVP (2.0 Units/kg), AlP + milrinone (0.25 mg/kg) and AlP + AVP + milrinone. After treatment, the animals were connected to an electronic cardiovascular monitoring device to monitor electrocardiographic (ECG) parameter. Finally, oxidative stress biomarkers, mitochondrial complex activities, ADP/ATP ratio and apoptosis were evaluated on the heart tissues. Results indicated that AlP administration induced ECG abnormalities along with a decline in blood pressure and heart rate. AVP and milrinone significantly ameliorated these changes in all treated groups. Considerable protective effects on oxidative stress biomarkers, complex IV activity, ADP/ATP ratio and caspase-3 and -9 activities in treated groups were also found. These findings were supported by flow cytometry assay of cardiomyocytes. In conclusion, administration of AVP and milrinone, not only improve cardiovascular functions in AlP poisoned rats in the short time, but after a long time can also restore mitochondrial function and ATP level and reduce the oxidative damage, which prevent cardiomyocytes from entering the apoptotic phase. © 2015 Elsevier Ltd.
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