Record Details

Combination Therapy with Andrographolide and D-Penicillamine Enhanced Therapeutic Advantage over Monotherapy with D-Penicillamine in Attenuating Fibrogenic Response and Cell death in the Periportal zone of Liver in Rats during Copper Toxicosis

EPrints@IICB

View Archive Info
 
 
Field Value
 
Title Combination Therapy with Andrographolide and D-Penicillamine Enhanced
Therapeutic Advantage over Monotherapy with D-Penicillamine in Attenuating
Fibrogenic Response and Cell death in the Periportal zone of Liver in Rats during
Copper Toxicosis
 
Creator Nath Roy, Dijendra
Sen, Gargi
Dutta Chowdhury, Kaustav
Biswas, Tuli
 
Subject Cell Biology & Physiology
 
Description Long treatment regime with D-penicillamine is needed before it can exert clinically meaningful benefits in the
treatment of copper toxicosis. The consequence of long-term D-penicillamine treatment is associated with
numerous side effects. The limitations of D-penicillamine monotherapy prompted us to search for more
effective treatment strategies that could decrease the duration of D-penicillamine therapy. The present study
was designed to evaluate the therapeutic potential of D-penicillamine in combination with another
hepatoprotective drug, andrographolide in treatment of copper toxicosis in rats. D-penicillamine treatment
led to the excretion of copper through urine. Addition of andrographolide to D-penicillamine regime appeared
to increase protection of liver by increasing the biliary excretion of copper and reduction in cholestatic injury.
The early removal of the causative agent copper during combination treatment was the most effective
therapeutic intervention that contributed to the early rectification of fibrosis in liver. Combination treatment
reduced Kupffer cells accumulation and TNFα production in liver of copper exposed rats. In particular,
andrographolide mediated the anti-inflammatory effect by inhibiting the cytokine production. However,
another possible mechanism of cytoprotection of andrographolide was decreasing mitochondrial production
of superoxide anions that resulted in better restoration of mitochondrial dysfunction during combination
therapy than monotherapy. Furthermore, ROS inhibition by combination regimen resulted in significant
decline in activation of caspase cascade. Inhibition of caspases attenuated apoptosis of hepatocytes, induced
by chronic copper exposure. In summary, this study suggested that added benefit of combination treatment
over use of either agent alone in alleviating the hepatotoxicity and fibrosis associated with copper toxicosis.
 
Publisher Elsevier
 
Date 2011
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1348/1/TOXICOLOGY_AND_APPLIED_PHARMACOLOGY__250__(1)_54%2D68_;2011[140].pdf
Nath Roy, Dijendra and Sen, Gargi and Dutta Chowdhury, Kaustav and Biswas, Tuli (2011) Combination Therapy with Andrographolide and D-Penicillamine Enhanced Therapeutic Advantage over Monotherapy with D-Penicillamine in Attenuating Fibrogenic Response and Cell death in the Periportal zone of Liver in Rats during Copper Toxicosis. Toxicology and Applied Pharmacology, 250 (1). pp. 54-68.
 
Relation http://dx.doi.org/10.1016/j.taap.2010.09.027
http://www.eprints.iicb.res.in/1348/