Fig 1.
Effects of procainamide on mean arterial pressure in endotoxemic rats.
Depicted are the changes during the experimental period in different groups of animals that received saline at time 0 (Control, n = 8), received saline as in Control group and then received procainamide at 1 h (Control + Procainamide, n = 8), received LPS at time 0 (LPS, n = 10), and received LPS at time 0 and then received procainamide at 1 h (LPS + Procainamide, n = 10). Data are expressed as mean ± SEM. *P < 0.05, all versus Control rats; #P < 0.05, with versus without procainamide in LPS rats
Fig 2.
Effects of procainamide on blood glucose in endotoxemic rats.
Depicted are the changes during the experimental period in different groups of animals that received saline at time 0 (Control, n = 8), received saline as in Control group and then received procainamide at 1 h (Control + Procainamide, n = 8), received LPS at time 0 (LPS, n = 10), and received LPS at time 0 and then received procainamide at 1 h (LPS + Procainamide, n = 10). Data are expressed as mean ± SEM. *P < 0.05, all versus Control rats; #P < 0.05, with versus without procainamide in LPS rats.
Table 1.
Effects of procainamide on organ function/injury in LPS-induced endotoxemic rats.
Fig 3.
Effects of procainamide on plasma nitric oxide (NO) in endotoxemic rats.
Depicted are the changes during the experimental period in different groups of animals that received saline at time 0 (Control, n = 5), received saline as in Control group and then received procainamide at 1 h (Control + Procainamide, n = 5), received LPS at time 0 (LPS, n = 5), and received LPS at time 0 and then received procainamide at 1 h (LPS + Procainamide, n = 5). Data are expressed as mean ± SEM. *P < 0.05, all versus Control rats; #P < 0.05, with versus without procainamide in LPS rats.
Fig 4.
Effects of procainamide on superoxide levels in (A) aortas, (B) lungs, (C) livers, and (D) kidneys obtained from endotoxemic rats. Depicted are changes at the end of experiments (at 6 h) in different groups of animals that received saline at time 0 (Control, n = 6), received saline as in Control group and then received procainamide at 1 h (Control + Procainamide, n = 6), received LPS at time 0 (LPS, n = 6), and received LPS at time 0 and then received procainamide at 1 h (LPS + Procainamide, n = 6). Data are expressed as mean ± SEM. *P < 0.05, all versus Control rats; #P < 0.05, with versus without procainamide in LPS rats.
Fig 5.
(A) Representative histopathologic features and (B) polymorphonuclear neutrophil (PMN) infiltration index of lung tissue sections obtained from endotoxemic rats. Depicted are changes in PMN infiltration index at the end of experiment (at 6 h) in different groups of animals that received saline at time 0 (Control, n = 3), received saline as in Control group and then received procainamide at 1 h (Control + Procainamide, n = 3), received LPS at time 0 (LPS, n = 3), and received LPS at time 0 and then received procainamide at 1 h (LPS + Procainamide, n = 3). Data are expressed as mean ± SEM. *P < 0.05, all versus Control rats; #P < 0.05, with versus without procainamide in LPS rats. Arrows represent neutrophil infiltration. Original magnification x 200.
Fig 6.
(A) Representative histopathologic features and (B) polymorphonuclear neutrophil (PMN) infiltration index of liver tissue sections obtained from endotoxemic rats. Depicted are changes in PMN infiltration index at the end of experiment (at 6 h) in different groups of animals that received saline at time 0 (Control, n = 3), received saline as in Control group and then received procainamide at 1 h (Control + Procainamide, n = 3), received LPS at time 0 (LPS, n = 3), and received LPS at time 0 and then received procainamide at 1 h (LPS + Procainamide, n = 3). Data are expressed as mean ± SEM. *P < 0.05, all versus Control rats; #P < 0.05, with versus without procainamide in LPS rats. Arrows represent neutrophil infiltration. Original magnification x 400.
Fig 7.
(A) Detection of 5-methylcytosine by immunohistochemistry and (B) the numbers of 5-methylcytosine positive cells in the lungs obtained from different groups of animals. Depicted are changes in the numbers of lung 5-methylcytosine positive cells at the end of experiment (at 6 h) in different groups of rats that received saline at time 0 (Control, n = 3), received saline as in Control group and then received procainamide at 1 h (Control + Procainamide, n = 3), received LPS at time 0 (LPS, n = 3), and received LPS at time 0 and then received procainamide at 1 h (LPS + Procainamide, n = 3). Data are expressed as mean ± SEM. *P < 0.05, all versus Control rats; #P < 0.05, with versus without procainamide in LPS rats. Original magnification x 400.
Fig 8.
Effects of procainamide on DNMT1 levels in the lungs obtained from different groups of animals.
Depicted are changes in lung DNMT1 levels at the end of experiment (at 6 h) in different groups of rats that received saline at time 0 (Control, n = 4), received saline as in Control group and then received procainamide at 1 h (Control + Procainamide, n = 4), received LPS at time 0 (LPS, n = 7), and received LPS at time 0 and then received procainamide at 1 h (LPS + Procainamide, n = 7). Data are expressed as mean ± SEM. *P < 0.05, all versus Control rats; #P < 0.05, with versus without procainamide in LPS rats.
Fig 9.
Effects of procainamide on the expressions of (A) DNMT3a and (B) DNMT3b in the lungs obtained from different groups of animals. Depicted are changes in lung DNMT3a and DNMT3b expressions at the end of experiment (at 6 h) in different groups of rats that received saline at time 0 (Control, n = 3), received saline as in Control group and then received procainamide at 1 h (Control + Procainamide, n = 3), received LPS at time 0 (LPS, n = 3), and received LPS at time 0 and then received procainamide at 1 h (LPS + Procainamide, n = 3). Data are expressed as mean ± SEM. *P < 0.05, all versus Control rats; #P < 0.05, with versus without procainamide in LPS rats
Fig 10.
Effects of hydralazine on (A) mean arterial pressure, (B) blood glucose, (C) alanine aminotransferase (ALT), (D) creatinine (CRE), (E) blood urea nitrogen (BUN), and (F) lactate dehydrogenase (LDH) in endotoxemic rats. Depicted are the changes during the experimental period in different groups of animals that received saline at time 0 (Control, n = 6), received saline as in Control group and then received hydralazine at 0.5 h (Control + Hydralazine, n = 6), received LPS at time 0 (LPS, n = 6), and received LPS at time 0 and then received hydralazine at 0.5 h (LPS + Hydralazine, n = 6). Data are expressed as mean ± SEM. *P < 0.05, all versus Control rats; #P < 0.05, with versus without hydralazine in LPS rats.
Table 2.
Effects of procainamide on survival rate in LPS-induced endotoxemic rats.
Fig 11.
Clustered display of microarray data from lung tissue.
Depicted are the changes in different groups of animals that received saline at time 0 (Control), received saline as in Control group and then received hydralazine at 0.5 h (Control + Hydralazine), received LPS at time 0 (LPS), and received LPS at time 0 and then received hydralazine at 0.5 h (LPS + Hydralazine). Up-regulated and down-regulated genes are symbolized in red and green colors, respectively.
Table 3.
Effects of procainamide on gene expression in LPS-induced endotoxemic rats.
Fig 12.
Effects of procainamide on IL27RA methylation in the lung of endotoxemic rat.
The 532 bp amplicon corresponds to the rat IL27RA promoter region from -401 to +131 (from the transcription start site of IL27RA). Sixteen CpG dinucleotides within the CpG islands were examined and denoted as open circle (unmethylated) and closed circle (methylated).
Fig 13.
Effects of procainamide on the expressions of (A) IL27RA mRNA and (B) IL27RA protein in the lungs obtained from different groups of animals. Depicted are changes in lung IL27RA mRNA and protein expressions at the end of experiment (at 6 h) in different groups of rats that received saline at time 0 (Control, n = 4), received saline as in Control group and then received procainamide at 1 h (Control + Procainamide, n = 4), received LPS at time 0 (LPS, n = 4), and received LPS at time 0 and then received procainamide at 1 h (LPS + Procainamide, n = 4). Data are expressed as mean ± SEM. *P < 0.05, all versus Control rats; #P < 0.05, with versus without procainamide in LPS rats