Effect of hydro-alcoholic extract of Panax ginseng and Ampicillin treatment in an animal model of Listeria monocytogenes-induced endocarditis.

Objective: Endocarditis is a rare but serious infection caused by Listeria monocytogenes. Panax ginseng demonstrated multiple immunomodulatory effects in earlier studies. Ampicillin is known as an effective antibiotic in the treatment of this disease. Therefore, this study aimed to evaluate the effect of hydro-alcoholic extract of P. ginseng and ampicillin treatment in an animal model of Listeria monocytogenes-induced endocarditis. Materials and Methods: Thirty mice, 5-7 weeks old, were randomly divided into five groups (n=6) including Healthy Control, Infected, Ampicillin (20 mg/kg, subcutaneous) treatment, Ginseng (0.025 mg/kg, intraperitoneal) treatment, and Ginseng (0.025 mg/kg, intraperitoneal) +Ampicillin (15 mg/kg, subcutaneous) treatment groups. The concentration of cytokines in heart tissue, such as IL-1 (interleukine-1), IL-6, IL-8, and TNF-α (Tumor Necrosis Factor-α), was measured. Histopathological changes were evaluated in heart tissues. Results: The levels of cytokines were significantly decreased in the Ampicillin+Ginseng treated group compared to the other experimental groups. Microscopically, pathologic changes in heart tissue were concomitant with biochemical findings, which in the infected group, neutrophils and mononuclear cells infiltration in endocardial tissue, myocardial cell necrosis, and edema were detectable. The Ampicillin+Ginseng group showed no significant changes compared to the normal control group. Conclusion: This study showed that ginseng hydro-alcoholic extract plus ampicillin has better efficacy than the extract or antibiotic alone against experimental endocarditis caused by Listeriosis.

Role of four-week resistance exercise in preserving the heart against ischaemia-reperfusion-induced injury.

OBJECTIVE: We studied the cardioprotective effect of resistance training against ischaemia-reperfusion-induced injury. METHODS: Forty male rats were divided into trained and sedentary groups (n = 20 for each). The trained rats were exercised at 12 repetitions/set, four sets/day and five days/week for four weeks. Transient regional ischaemia of the left anterior descending coronary artery (40 min) was followed by 80 min of reperfusion. RESULTS: Baseline developed and diastolic pressures and coronary flow were similar in the two groups. While diastolic pressure increased and developed pressure and coronary flow decreased in both the ischaemic and perfusion periods (as indices of cardiac damage), there were no statistically significant differences between the trained and sedentary groups in these parameters. Resistance training did not significantly change the infarct size and apoptosis rate. CONCLUSION: We did not see a cardioprotective effect of resistance exercise against ischaemia-reperfusion-induced injury in this study. A precise conclusion about this issue needs more investigations.

Ambivalent effects of atorvastatin on angiogenesis, epidermal cell proliferation and tumorgenesis in animal models.

BACKGROUND: A growing body of preclinical data indicates that statins may possess antineoplastic properties; however, some studies have raised the possibility that statins may also have carcinogenic potential. METHODS: An air pouch model was used for angiogenesis. Single or multiple applications of croton oil on the back of Swiss albino mice with or without initiation by dimethylbenz(a)antheracene (DMBA) were used to evaluate the skin tumorgenesis, ultrastructural and histological alterations. RESULTS: Atorvastatin (orally, 10 mg/kg/day) produced a significant (P<0.05) reduction in angiogenesis. Concurrent administration of mevalonate reversed the anti-angiogenic effect of atorvastatin. However, local injection of atorvastatin (200 µg) into the pouches induced a significant (P<0.5) increase in angiogenesis that was not reversed by co-administration of mevalonate. The disturbance of cell polarity, inflammatory response, thickness of epidermal layer, and mitotic index induced by croton oil were inhibited markedly and dose-dependently (P<0.001) by pre-treatment with atorvastatin. In spite of the strong anti-inflammatory and anti-proliferative effects of atorvastatin on epidermal cell proliferation, it was identified that the same doses of atorvastatin in DMBA-initiated and croton oil-promoted skin tumorgenesis in mice increased the incidence of tumors and their conversion into malignant carcinoma. CONCLUSION: The reasons for these discrepancies remain unclear, and could be related to ambivalent effects of atorvastatin on angiogenesis or to specific differences in the experimental conditions. It is suggested that the pro-angiogenic effect of the drug, which could be responsible for promotion of skin tumors, is independent of the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibition that can be mediated directly by atorvastatin.

Combined atorvastatin and coenzyme Q10 improve the left ventricular function in isoproterenol-induced heart failure in rat.

The effect of atorvastatin on cardiac remodeling, function, and homodynamic parameters in isoproterenol-induced heart failure was evaluated in the present study. A subcutaneous injection of isoproterenol (5mg/kg/day) for 10 days was used for the induction of heart failure. Isoproterenol administration produced intensive myocardial necrosis and fibrosis with a significant decrease in the arterial pressure indices, heart rate, contractility (LVdP/dt(max)) and relaxation (LVdP/dt(min)), but an increase in the left ventricular end-diastolic pressure. Rats were randomly assigned to control, treatment with only atorvastatin, and treatment with atorvastatin plus coenzyme Q10. Histopathological analysis showed a marked attenuation of myocyte necrosis and interstitial fibrosis in all atorvastatin treated groups (P<0.001). A low dose of atorvastatin (5mg/kg/day) significantly improved the left ventricular systolic pressure, contractility and relaxation (P<0.01). On the contrary, a high dose of atorvastatin (20mg/kg/day) worsened the isoproterenol-induced left ventricular dysfunction by a further reduction of LVdP/dt(max) from +2780 ± 94 to +1588 ± 248 (mmHg/s; P<0.01) and LVdP/dt(min) from -2007 ± 190 to -2939 ± 291 (mmHg/s; P<0.05). Co-administration of coenzyme Q10 with atorvastatin reversed the hemodynamic depression and the left ventricular dysfunction to a high level (P<0.001). There was a lower level of LVEDPs in the atorvastatin+coenzyme Q10 treated groups (3 ± 1 and 4 ± 1.4 versus 8 ± 3.5 and 14 ± 3.6 mmHg, respectively), thereby suggesting improvement in the myocardial stiffness by the combined coenzyme Q10 and atorvastatin treatment. The atorvastatin therapy attenuated myocardial necrosis and fibrosis in isoproterenol-induced heart failure. However, a high dose of the drug considerably worsened the left ventricular dysfunction and hemodynamic depression, which was reversed by coenzyme Q10 co-administration.

8-OH-DPAT prevents morphine-induced apoptosis in rat dorsal raphe nucleus: a possible mechanism for attenuating morphine tolerance.

BACKGROUND: Previously, we found that activation of serotonin 1A (5-HT1A) receptors in the dorsal raphe nucleus (DRN) decreased the development of tolerance to the analgesic effect of morphine. It has been indicated that tolerance to the analgesic effect of morphine is associated with apoptosis in the central nervous system. In this investigation we attempted to evaluate the effect of 8-OH-DPAT (8-hydroxy-2-[di-n-propylamino]tetralin), a specific 5-HT1A receptor agonist, on morphine-induced tolerance and apoptosis in rat DRN. METHODS: Nociception was assessed using a hotplate apparatus. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method was used to analyze apoptosis. RESULTS: Tolerance to the analgesic effect of morphine was complete by 10 days after morphine administration (5 mg/kg/d, i.p.), whereas a significant analgesic effect was observed through the 10th day in 8-OH-DPAT-treated animals. Furthermore, the results showed that the number of TUNEL positive cells had been increased in morphine-tolerant rats (control group: morphine, i.p. + saline, intra-DRN) in comparison with the saline-treated animals. The results also indicated that 8-OH-DPAT (2, 4, and 8 µg/rat/d) attenuated the number of apoptotic cells in the DRN in comparison with the control group. However, 8-OH-DPAT (8 µg/rat/d, intra-DRN) failed to reduce morphine-induced apoptosis in the presence of the 5-HT1A receptor antagonist, NAN-190 (6 µg/rat/d, intra-DRN). CONCLUSION: We found that intra-DRN injection of a specific 5-HT1A receptor agonist attenuated morphine-induced apoptosis in rat DRN, which may have a key role in morphine tolerance.

Long-term exercise training affects age-induced changes in HSP70 and apoptosis in rat heart.

The aim of this study was to test the effects of age and long-term exercise training on antioxidant, heat shock protein 70 (HSP70) expression and apoptosis by comparing the hearts of sedentary and trained rats. Training groups went under 3-, 6- and 9-months of regular exercise (25 m/min with a 0% slope, 60 min/day and 6 days/week). Level of glutathione increased with age in trained and sedentary control rats but level of this factor unchanged by training. Activity of mitochondrial superoxide dismutase (mtSOD) increased in heart homogenates of 6- and 9-months trained animals as compared with their sedentary. The rates of apoptosis were increased with age but level of apoptosis in 9-months trained group was significantly lower than corresponding sedentary. Levels of HSP70 expression were significantly decreased with age while long-term training induced marked increase in HSP70 expression levels. These results show that a long-term regular exercise affects age-induced changes in mtSOD, HSP70 and apoptosis as it increases mtSOD activities and HSP70 expression levels and elicits a marked reduction in apoptosis rate in rat myocardium. However, a shorter training program is not effective.