Abstract

To study the ameliorating effects of curcumin in lipopolysaccharide (LPS) induced cardiac hypertrophy, mice were assigned to 4 groups (3 males and 3 females in each group): (A) control, (B) curcumin: 100 μg/kg of body weight by intraperitoneal route (IP), (C) LPS: 60 mg/kg (IP), and (D) LPS + curcumin: both at previously stated concentrations by IP route. All mice were sacrificed as 12 hr and 24 hrs groups accordingly after LPS injection. The hearts were collected, photographed for cardiomegaly, and weighed to compare heart weight/brain weight (HW/BW) in mg/mg. For immunohistochemistry, the tissue sections were exposed to histone H3, H4 and acetylated histone H3, H4 antibody. LPS induced a significant increase in histone acetylation as shown by intense staining. In curcumin + LPS treated mice nuclear staining was similar to the control group indicating that curcumin traversed the histone acetylation activity of the LPS. To further check the mechanism of action of curcumin, p300 protein acetylation levels were analyzed. This study suggests that the probable mechanism of action of curcumin is via the reduction of p300 HAT activity.

Highlights

  • In the United States, foodborne pathogens cause 76 million illnesses, 325,000 hospitalizations, and 5,000 deaths annually [1]

  • The results of the present study indicate that inhibition of histone acetylation is a key mechanism for the anti-cardiac hypertrophy activity of curcumin and that p300HAT serves as its molecular target. p300 may maintain basal function in the normal heart but it promotes cardiac hypertrophy under LPS infusion

  • We can conclude from our study that curcumin attenuated LPS induced cardiac hypertrophy in vivo

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Summary

Introduction

In the United States, foodborne pathogens cause 76 million illnesses, 325,000 hospitalizations, and 5,000 deaths annually [1]. Infections with gram-negative bacteria may lead to endotoxemia caused by lipopolysaccharides (LPS) which is a complex of glycolipids made up of two distinct regions. These are hydrophilic polysaccharide region (composed of O antigen and core oligosaccharide) and hydrophobic regions known as lipid A [3]. Acetylation of histones reduces their overall positive charge, decreasing their tight interactions with negatively charged DNA [5]. It activates the transcriptional pathway and gene expression [6]. HATs (histone acetyltransferases) and HDACs (histone deacetylases) activity determines the transcriptional activation or repression

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