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Year : 2012  |  Volume : 3  |  Issue : 4  |  Page : 349-350  

Old wine, old bottle, new customer


Department of Pharmacology, Indira Gandhi Medical College and Research Institute, Kadhirkamam, Puducherry, India

Date of Web Publication24-Nov-2012

Correspondence Address:
G Sivagnanam.
Department of Pharmacology, Indira Gandhi Medical College and Research Institute, Kadhirkamam, Puducherry
India
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Source of Support: None, Conflict of Interest: None


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How to cite this article:
Sivagnanam. G. Old wine, old bottle, new customer. J Pharmacol Pharmacother 2012;3:349-50

How to cite this URL:
Sivagnanam. G. Old wine, old bottle, new customer. J Pharmacol Pharmacother [serial online] 2012 [cited 2019 Jul 18];3:349-50. Available from: http://www.jpharmacol.com/text.asp?2012/3/4/349/103701


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The cheap injection that might be able to save a soldier's life.

It has been roughly estimated that it would take about 4 h for injured soldiers to receive a blood transfusion at a hospital. Researchers at Massachusetts General Hospital wondered whether histone deacetylase (HDAC) inhibitors could counter and prevent organ failure in instances of rapid blood loss. Pigs were divided into three groups and were drained of 60% of their blood. Group 1 received saline infusion, group 2 received valproic acid (HDAC inhibitor) injection, and group 3 blood transfusion. Survival at the end of 4 h was 25%, 86%, and 100%, respectively. A similar effect in humans by valproic acid can buy time drastically in soldiers who have suffered massive blood loss till blood transfusion is available. [1]


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It has been previously shown that valproic acid, an HDAC inhibitor, can improve survival in lethal models of hemorrhagic shock. [2]

Usage of corticosteroids as a therapy for numerous forms (e.g., septic, hypovolemic, traumatic, cardiogenic, etc.) of circulatory shock is well known, though the mechanism is unclear. Corticosteroids suppress the multiple inflammatory genes that are activated in asthmatic airways mainly by reversing histone acetylation of activated inflammatory genes. [3] A preliminary clinical trial has indicated that the broad spectrum HDAC inhibitor, valproic acid, has potent antiasthmatic activity. [4]

Whether corticosteroids as well as valproic acid affect the same HDAC to bring out the beneficial effects in shock is not known.

Ironically, there are case reports implicating valproic acid in the causation of shock. [5],[6]

Recently in rat models, a serum protein called claudin-3 has been shown to be elevated with a concurrent decrease in intestinal claudin-3 levels in hemorrhagic shock. These alterations were reversed by valproic acid treatment. In this study, claudin-3 has been suggested as a potential biomarker in hemorrhagic shock and its treatment. [7]

Whatever may be the mechanism, if valproic acid is shown to enhance survival time in hemorrhagic shock in humans, then it would occupy a status in the "must have drugs list" in the emergency department.

 
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1.Available from: http://www.uproxx.com/feature/2010/06/five-cool-recent-medical-advances-you-may-not-have-heard-about/#ixzz23WoqBZcu. [Last accessed 2012 Aug 14].  Back to cited text no. 1
    
2.Zacharias N, Sailhamer EA, Li Y, Liu B, Butt MU, Shuja F, et al. Histone deacetylase inhibitors prevent apoptosis following lethal hemorrhagic shock in rodent kidney cells. Resuscitation 2011;82:105-9.  Back to cited text no. 2
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3.Barnes PJ. Corticosteroids: The drugs to beat. Eur J Pharmacol 2006;533:2-14.  Back to cited text no. 3
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4.Lomia M, Chapichadze Z, Pruidze M, Platonov P. Efficacy of monotherapy with carbamazepine and valproic acid in patients with bronchial asthma: is asthma a neurological disease? Internet J Neurol 2005;4:1.   Back to cited text no. 4
    
5.Fernandez-Fernandez FJ, Garcia-Rego J, Garcia-Jimenez A, Sesma P. Hemorrhagic shock and fulminant hepatic failure associated with valproate. An Med Interna 1995;12:606-8.  Back to cited text no. 5
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6.White JR, Santos CS. Intravenous valproate associated with significant hypotension in the treatment of status epilepticus. J Child Neurol 1999;14:822-3.  Back to cited text no. 6
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7.Li Y, Liu B, Dillon ST, Fukudome EY, Kheirbek T, Sailhamer EA, et al. Identification of a novel potential biomarker in a model of hemorrhagic shock and valproic acid treatment. J Surg Res 2010;159:474-81.  Back to cited text no. 7
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