Role of inflammation, oxidative stress, and autonomic nervous system activation during the development of right and left cardiac remodeling in experimental pulmonary arterial hypertension.

This study investigated the impact of experimental pulmonary arterial hypertension (PAH) progression by evaluating morphometric and functional parameters, oxidative stress, autonomic nervous system (ANS) activation, and inflammation in the right (RV) and left (LV) ventricles. Male rats were first divided into two groups: monocrotaline (MCT) and control. The MCT group received a single MCT injection (60 mg/kg, intraperitoneal), while control received saline. The MCT and control groups were further divided into four cohorts based on how long they were observed: 1, 2, 3, and 4 weeks. Animals were submitted to echocardiographic and hemodynamic analysis. RV and LV were used for morphometric, biochemical, and histological measurements. Autonomic modulation was evaluated by cardiac spectral analysis, considering two components: low frequency (LF) and high frequency (HF). Lung and liver weight was used for morphometric analysis. MCT induced 100% mortality at 4 weeks. In the RV, disease progression led to mild inflammation and enhanced reactive oxygen species (ROS) in week 1, followed by moderate inflammation, ROS production, and hypertrophy in week 2. By week 3, there was moderate inflammation, oxidative stress, and ANS imbalance, with development of right heart dysfunction. LV biochemical changes and inflammation were observed at week 3. The initial changes appeared to be related to inflammation and ROS, and the later ones to inflammation, oxidative stress, and ANS imbalance in MCT animals. This study reinforces the severity of the disease in the RV, the late effects in the LV, and the role of ANS imbalance in the development of heart dysfunction.

Profile of pterostilbene-induced redox homeostasis modulation in cardiac myoblasts and heart tissue.

This study was designed to investigate the effect of pterostilbene (PTS) on cardiac oxidative stress in vitro, as this is a simple and promising methodology to study cardiac disease. Cardiac myoblasts (H9c2 cells) and homogenised cardiac tissue were incubated with the PTS and cyclodextrin (PTS + HPßCD) complex for 1 and 24 h, respectively, at concentrations of 50µM for the cells and 25 and 50µM for cardiac tissue. The PTS + HPßCD complex was used to increase the solubility of PTS in water. After the pretreatment period, cardiomyoblasts were challenged with hydrogen peroxide (6.67µM) for 10 min, while cardiac tissue was submitted to a hydroxyl radical generator system (30 min). Cellular viability, oxidative stress biomarkers (e.g. total reactive oxygen species (ROS), carbonyl assay and lipoperoxidation) and the antioxidant response (e.g. sulfhydryl and the antioxidant enzyme activities of superoxide dismutase, catalase and glutathione peroxidase) were evaluated. In cardiomyoblasts, the PTS + HPßCD complex (50µM) increased cellular viability. Moreover, the PTS + HPßCD complex also significantly increased sulfhydryl levels in the cells submitted to an oxidative challenge. In cardiac tissue, lipid peroxidation, carbonyls and ROS levels were significantly increased in the groups submitted to oxidative damage, while the PTS + HPßCD complex significantly reduced ROS levels in these groups. In addition, the PTS + HPßCD complex also provoked increased catalase activity in both experimental protocols. These data suggest that the PTS + HPßCD complex may play a cardioprotective role through a reduction of ROS levels associated with an improved antioxidant response.

Lack of oncogenicity of wood creosote, the principal active ingredient of Seirogan, an herbal antidiarrheal medication, in Sprague-Dawley rats.

Seirogan, an herbal medicine containing wood creosote (tablets, 10.0% w/w), has been developed and marketed for almost a century in various countries for the control of acute diarrhea and treatment of associated symptoms, such as abdominal cramping. Wood creosote (CAS no. 8021-39-4) is a mixture of simple phenolic compounds, including guaiacol and creosol and related compounds, and is chemically distinct from, and should not be confused with, coal tar creosote, a known carcinogen. In the current study, the oncogenic potential of wood creosote was assessed in a 96/103-week oral gavage study in Sprague-Dawley rats. Groups of 60 rats/sex received wood creosote at dose levels of 20, 50, or 200 mg/kg body weight [bw]/day. An additional group of rats received the vehicle, 0.5% carboxymethylcellulose in deionized, distilled water, at the same dose volume as the treatment groups (10 ml/kg) and served as the controls. Treatment-related decreases in survival, body weight, and food consumption, as well as increased incidences of clinical signs that included rales, decreased activity, and salivation, were noted at 200 mg/kg bw/day when compared with the control group. There was an increased incidence of reddened and edematous lungs in rats from the 200 mg/kg bw/day group that died during the study. The lung findings were suggestive of test article aspiration during dose administration or agonal aspiration preceding and possibly resulting in death, especially because these observations were not seen in animals that survived to scheduled sacrifice. Additionally, phenols are generally recognized as having corrosive properties. There were no changes in clinical pathology and no increases in neoplastic or non-neoplastic lesions, excluding the lung findings, related to treatment with wood creosote at any dose level. Although the results of this study indicate that the maximum tolerated dose of wood creosote was met or exceeded at 200 mg/kg bw/day, there was no evidence of oncogenicity at any dose level. The lack of any evidence of oncogenicity supports the safety profile of the active ingredient in Seirogan, wood creosote.

Mastitis: effect of pH, temperature, and emollients on disinfecting action of N,N-dimethyldodecanamine.

Growth inhibition of bacteria over time by N,N-dimethyldodecanamine, a tertiary alkyl amine, was studied to evaluate disinfecting action with changes in pH and temperature and with addition of emollients. Because alkyl amines have limited solubility in aqueous solutions, the effect of pH on solubility of the tertiary amine was determined. Non-growing cultures of Streptococcus agalactiae or Escherichia coli were added to sterile buffer or buffer containing the amine, and at specific intervals aliquots were removed, neutralized in a lecithin/Tween 80 quencher, and then plated to determine the number of surviving bacteria per plate. Survival curves were used to determine the effect of changing environmental conditions on antimicrobial activity. Antimicrobial activity was greater at pH 7 than at pH 8 and was least at pH 6. Increases in temperature from 20 to 40 degrees C caused a corresponding increase in antimicrobial activity. Addition of up to 10% glycerin or propylene glycol caused no significant decrease in antimicrobial activity of the tertiary amine.

Mastitis: II. Evaluation of antimicrobial amines for use as teat dips.

Recent proposals by the Food and Drug Administration to regulate teat dips as drugs have led to a search for safer teat dip ingredients. Primary, secondary, and tertiary alkyl amines (carbon-10 to -18 chain length) inhibit growth of mastitic bacteria (Streptococcus agalactiae, Streptococcus uberis, Staphylococcus aureus, Escherichi coli, Klebsiella pneumoniae) in a broth tube culture assay. Since carbon-13 compounds were active, a carbon-13 primary (tridecanamine hydrochloride), secondary methyl (N-methyltridecanamine), secondary ethyl (N-ethyltridecanamine), tertiary dimethyl amine (N, N-dimethyltridecanamine), and carbon-12 quaternary amine (N, N, -trimethyldodecaneammonium chloride) were tested for their ability to reduce experimentally applied populations of S. agalactiae or E. coli on the bovine teat surface. The five compounds were compared at concentrations of 100, 500, 1,000, 3,000, 7,000, and 10,000 ppm. Activity was greater against the gram-positive S. agalactiae than against the gram-negative E. coli. The tertiary amine was most active, producing a log reduction of 4 (reduction of bacterial number from 10(6) to 10(2)) at a concentration of 3,000 ppm in the teat dip. The relative order of effectiveness for the amines was: dimethyl tertiary greater than methyl secondary greater than ethyl secondary greater than primary = quaternary. The results suggest that these amines may be useful as potent, effective antibacterial agents for incorporation into teat dips.