Mir Imam Ibne Wahed

Antimicrobial activity and cytotoxicity of Trapa bispinosa

The extracts of Trapa bispinosa showed interesting antimicrobial activity against Gram-positive and Gram-negative test organisms and significant cytotoxic activity.

Effects of Eplerenone, a Selective Aldosterone Blocker, on the Progression of Left Ventricular Dysfunction and Remodeling in Rats with Dilated Cardiomyopathy

Aldosterone blockade reduces morbidity and mortality in patients with heart failure. We studied the effects of eplerenone, a novel aldosterone blocker, on the progression of left ventricular dysfunction and remodeling in rats with dilated cardiomyopathy after autoimmune myocarditis. Twenty-eight days after immunization, the surviving Lewis rats were randomized to 1 month’s oral treatment with low-dose eplerenone (group L), high-dose eplerenone (group H) or vehicle (group V). Five of 15 (33%) rats in group V and 3 of 15 (20%) rats in group L died during the course of treatment. High-dose eplerenone significantly reduced cardiomyocyte hypertrophy, heart weight and heart weight to body weight ratio. Eplerenone improved left ventricular function in a dose-dependent manner. Central venous pressure and left ventricular end-diastolic pressure were lower, and ±dP/dt and fractional shortening were higher in group H than group V. Eplerenone also attenuated myocardial fibrosis and reduced left ventricular mRNA expressions of TGF-β1 and collagen-III. Our results indicate that treatment with eplerenone improved left ventricular dysfunction and attenuated left ventricular remodeling in rats with heart failure.

Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-κB translocation

&NA; Curcumin, a phenolic compound, has a wide spectrum of therapeutic effects such as antitumor, anti‐inflammatory, anti‐cancer and so on. The study aimed to investigate the underlying mechanisms of curcumin to protect liver damage and progression of non‐alcoholic steatohepatitis (NASH) in a novel NASH‐hepatocellular carcinoma (HCC) mouse model. To induce this model neonatal C57BL/6J male mice were exposed to low‐dose streptozotocin and were fed a high‐fat diet (HFD) from the age of 4 weeks to 14 weeks. Curcumin was given at 100 mg/kg dose daily by oral gavage started at the age of 10 weeks and continued until 14 weeks along with HFD feeding. We found that curcumin improved the histopathological changes of the NASH liver via reducing the level of steatosis, fibrosis associated with decreasing serum aminotransferases. In addition, curcumin treatment markedly reduced the hepatic protein expression of oxidative stress, pro‐inflammatory cytokines, and chemokines including interferon (IFN) &ggr;, interleukin‐1&bgr; and IFN&ggr;‐inducible protein 10, in NASH mice. Furthermore, curcumin treatment significantly reduced the cytoplasmic translocation of high mobility group box 1 (HMGB1) and the protein expression of toll like receptor 4. Nuclear translocation of nuclear factor kappa B (NF‐&kgr;B) was also dramatically attenuated by the curcumin in NASH liver. Curcumin treatment effectively reduced the progression of NASH to HCC by suppressing the protein expression of glypican‐3, vascular endothelial growth factor, and prothrombin in the NASH liver. Our data suggest that curcumin reduces the progression of NASH and liver damage, which may act via inhibiting HMGB1‐NF‐&kgr;B translocation. HighlightsNASH‐HCC mouse model involves the increased HMGB1 and NF‐&kgr;B translocation.In this model, oxidative stress and inflammation were significantly increased.It involves the activation of lipogenesis and fibrosis in NASH liver.Curcumin treatment reduced these oxidative stress, inflammation and lipogenesis.Curcumin markedly attenuated fibrosis, HMGB1‐NF‐&kgr;B translocation and its signaling.

Inhibition of progression of heart failure and expression of TGF-β1 mRNA in rats with heart failure by the ace inhibitor quinapril

Summary: The cardioprotective effects of quinapril, an angiotensinconverting enzyme inhibitor, were studied in a rat model of heart failure. Twenty‐six rats were divided into two groups: one given 20 mg/kg/day quinapril (n = 11), and controls given 0.5% methylcellulose (n = 15). After oral administration for 1 month, quinapril reduced heart weight (from 1.28 ± 0.05 to 0.87 ± 0.02 g; p < 0.05) without changing body weight. Quinapril lowered left ventricular end‐diastolic pressure (from 14.1 ± 2.0 to 6.6 ± 1.5 mmHg; p < 0.05) and central venous pressure (from 2.7 ± 0.9 to 0.7 ± 0.4 mmHg), and increased ± dP/dt (from +2409 ± 50 to +3569 ± 169 mmHg/s, and from ‐2318 ± 235 to ‐3960 ± 203 mmHg/s; both p < 0.01). The area of myocardial fibrosis was markedly reduced by quinapril (6 ± 3%) as compared with controls (29 ± 6%; p < 0.01). Expression of transforming growth factor (TGF)‐&bgr;1 mRNA was markedly increased in controls as compared with age‐matched normal rats. The increase in level of TGF‐&bgr;1 mRNA was significantly suppressed by quinapril (from 17.1 ± 6.2 to 9.00 ± 2.40; p < 0.05). These observations indicated that quinapril has cardioprotective effects on heart failure, and that the beneficial effects may be partly explained by attenuation of fibrotic response through suppression of TGF‐&bgr;1 mRNA expression.

Effects of angiotensin-II receptor blocker candesartan cilexetil in rats with dilated cardiomyopathy.

We examined effects of an angiotensin-II receptor blockers, candesartan cilexetil, in rats with dilated cardiomyopathy after autoimmune myocarditis. Candesartan cilexetil showed angiotensin-II blocking action in a dose-dependent manner in rats with dilated cardiomyopathy. Twenty-eight days after immunization, surviving Lewis rats were divided into four groups and given candesartan cilexetil at 0.05 mg/kg, 0.5 mg/kg or 5 mg/kg per day (Group-C0.05, n = 15, Group-C0.5, n = 15 and Group-C5, n = 15, respectively) or vehicle alone (Group-V, n = 15). After oral administration for 1 month, the left ventricular end-diastolic pressure and heart weight/body weight ratio were lower in Group-C0.05 (13.3± 1.1 mmHg and 3.7± 0.2 g/kg, respectively), in Group-C0.5 (8.0± 0.9 mmHg and 3.3± 0.1 g/kg, respectively) and in Group-C5 (5.5± 1 mmHg and 3.1± 0.1 g/kg, respectively) than in Group-V (13.5± 1.0 mmHg and 3.8± 0.2 g/kg, respectively). The area of myocardial fibrosis was also lower in Group-C0.05 (25± 3%), in Group-C0.5 (20± 3%), and in Group-C5 (12± 1%) than in Group-V (32± 4%). Furthermore, expressions of transforming growth factor-β1 and collagen-III mRNA were suppressed in Group-C0.05 (349± 23% and 395± 22%, respectively), Group-C0.5 (292± 81% and 364± 42%, respectively) and in Group-C5 (204± 63% and 259± 33%, respectively) compared with those in Group-V (367± 26% and 437± 18%, respectively). These results suggest that candesartan cilexetil can improve the function of inefficient heart. (Mol Cell Biochem 269: 137–142, 2005)

Comparative Effects of Perindopril with Enalapril in Rats with Dilated Cardiomyopathy

Summary: Angiotensin‐converting enzyme inhibitors have been shown to reduce morbidity and mortality in patients with heart failure. The angiotensin type‐1 blocking and cardioprotective properties of perindopril and enalapril were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. Enalapril at 20 mg/kg showed the same angiotensin type‐1 blocking action as perindopril at 2 mg/kg in rats with heart failure. Twenty‐eight days after immunization, surviving Lewis rats (90/120 = 75%) were divided into six groups and administered perindopril at 0.02, 0.2 and 2 mg/kg per day (Groups P0.02, P0.2 and P2), enalapril at 2 and 20 mg/kg per day (Groups E2 and E20) or vehicle alone (Group V, all groups n = 15). After oral administration for 1 month, four of 15 (27%) rats in Group V, and two (13%) in Groups P0.02 and E2 died. None of the animals in Groups P0.2, P2 and E20, or normal rats (Group N) died. Although both angiotensin‐converting enzyme inhibitors improved ventricular function in a dose‐dependent manner, the left ventricular end‐diastolic pressure and area of myocardial fibrosis were lower, and ± dP/dt was higher in Group P2 (4.9 ± 0.6 mmHg, 7.5 ± 1.4% and +2651 ± 254/ ‐2622 ± 189 mmHg/s, respectively) than in Group V (16.7 ± 1.3, 36 ± 2.6 and +2659 ± 176/‐2516 ± 205, respectively) and Group E20 (7.5 ± 2.5, 15.6 ± 2.0 and +2018 ± 110/‐2097 ± 102, respectively). Although the expression levels of transforming growth factor‐&bgr;1 and collagen‐III mRNA in Group V (36.3 ± 5.7 and 157.6 ± 12.7%) were significantly higher than those in Group N (19.6 ± 3.0 and 65.2 ± 1.5%, both p < 0.01), they were reduced in Group P2 (21.4 ± 5.9 and 75.2 ± 9.3%, both p < 0.01). These results suggest that although enalapril can block increases in blood pressure caused by circulating angiotensin type‐1, perindopril at 2 mg/kg may confer greater protection than enalapril at 20 mg/kg against injury from the renin‐angiotensin system in heart failure.

Bisoprolol improves survival in rats with heart failure

Summary: The cardioprotective effects of bisoprolol were studied in a rat model of severe heart failure induced by autoimmune myocarditis. Twenty‐eight days after immunization, Lewis rats were divided into four groups: 0.1 mg/kg/day bisoprolol (Group 0.1), 1.0 mg/kg/day bisoprolol (Group 1) and 10 mg/kg/day bisoprolol (Group 10), and vehicle (0.5% methylcellulose; Group V) (all groups, n = 13). After oral administration for 1 month, heart weight, mean blood pressure, heart rate, central venous pressure, peak left ventricular pressure, left ventricular end‐diastolic pressure, ± dP/dt, and area of fibrosis were measured. Although bisoprolol reduced heart rate (399 ± 11/min in Group V, 382 ± 10/min in Group 0.1, 348 ± 8/min in Group 1 and 302 ± 9/min in Group 10) and increased survival (62% in Group V, 69% in Group 0.1, and 100% in Group 1 and Group 10) in a dose‐dependent manner, this drug did not change heart weight, the area of myocardial fibrosis or hemodynamic parameters. These observations suggested that bisoprolol may improve survival independently of its effect on left ventricular function by reducing sudden death in patients with severe heart failure.

Quinapril inhibits progression of heart failure and fibrosis in rats with dilated cardiomyopathy after myocarditis

The cardioprotective properties of quinapril, an angiotensin-converting enzyme inhibitor, were studied in a rat model of dilated cardiomyopathy. Twenty-eight days after immunization of pig cardiac myosin, four groups rats were given 0.2 mg/kg (Q0.2, n = 11), 2 mg/kg (Q2, n = 11) or 20 mg/kg (Q20, n = 11) of quinapril or vehicle (V, n = 15) orally once a day. After 1 month, left ventricular end-diastolic pressure (LVEDP), ±dP/dt, area of myocardial fibrosis, and myocardial mRNA expression of transforming growth factor (TGF)-β1, collagen-III and fibronectin were measured. Four of 15 (27%) rats in V and two of 11 (18%) in Q0.2 died. None of the animals in Q2 or Q20 died. The LVEDP was higher and ±dP/dt was lower in V (14.1 ± 2.0 mmHg and +2409 ± 150/−2318 ± 235 mmHg/sec) than in age-matched normal rats (5.0 ± 0.6 mmHg and +6173 ± 191/−7120 ± 74 mmHg/sec; all p < 0.01). After quinapril treatment, LVEDP was decreased and ±dP/dt was increased in a dose-dependent manner (10.8 ± 1.8 mmHg and +3211 ± 307/−2928 ± 390 mmHg/sec in Q0.2, 9.4 ± 1.5 mmHg and +2871 ± 270/−2966 ± 366 mmHg/sec in Q2, and 6.6 ± 1.5 mmHg, and +3569 ± 169/−3960 ± 203 mmHg/sec in Q20). Increased expression levels of TGF-β1, collagen-III and fibronectin mRNA in V were reduced in Q20. Quinapril improved survival rate and cardiac function in rats with dilated cardiomyopathy after myocarditis. Furthermore, myocardial fibrosis was regressed and myocardial structure returned to nearly normal in animals treated with quinapril.

Contribution of sympathetic nervous system activity during administration of carvedilol in rats with dilated cardiomyopathy.

Summary: We investigated the contribution of the sympathetic nervous system (SNS) in maintaining blood pressure during administration of carvedilol in rats with dilated cardiomyopathy, and examined whether SNS hyperactivity induced by high‐dose carvedilol is related to severity of heart failure. The hypotensive effect of carvedilol in rats with heart failure (Group F) was not significantly different to that in rats without (Group N). However, enhancement of the plasma norepinephrine concentration during carvedilol administration in Group F was higher than in Group N. The constitutive plasma NE concentration in Group F (562 ± 146 pg/ml) was significantly higher than in Group N (203 ± 55 pg/ml) and there was a significant positive correlation between the heart weight to body weight ratio and the plasma norepinephrine concentration. Values for the maximal effect of the norepinephrine hypertensive effect during norepinephrine intravenous infusion (Emax) decreased, and plasma norepinephrine concentrations at half‐maximal effect of the norepinephrine hypertensive effect (EC50) increased in Group F compared with Group N (20.8 ± 6.1 and 28.6 ± 2.2 mmHg, and 4.5 ± 1.9 and 1.5 ± 0.2 ng/ml, respectively). These results suggested that the number of receptors (Emax) and sensitivity (EC50) to the norepinephrine hypertensive effect decreased in Group F. Changes in these parameters in Group F corresponded with the results of a &bgr;‐adrenergic receptor binding assay using I‐125 iodocyanopindolol (Bmax = 32 ± 4 in Group F and 53 ± 2 fmol/mg protein in Group N). These results showed that the SNS (presynaptic) activity increased and the SNS receptor sensitivity in the blood pressure regulation system decreased in heart failure. Therefore, high‐dose carvedilol treatment should be used with caution to avoid worsening heart failure.

Comparative effects of pranidipine with amlodipine in rats with heart failure.

The aim of the present study was to compare the cardioprotective properties of long-acting calcium channel antagonist pranidipine with amlodipine in rat model of heart failure induced by autoimmune myocarditis. Twenty-eight days after immunization the surviving rats were randomized for the oral administration of low-dose amlodipine (1 mg/kg/day), high-dose amlodipine (5 mg/kg/day), pranidipine (0.3 mg/kg/day) or vehicle (0.5% methylcellulose). After oral administration for 1 month, the animals underwent echocardiography and hemodynamic analysis. Histopathology, immunohistochemistry, and Western immunoblotting were carried out in the heart samples. Both pranidipine and high-dose amlodipine increased survival rate. Although the heart rate did not differ among the four groups, left ventricular end-diastolic pressure was significantly decreased and ±dP/dt was increased in the pranidipine- and high-dose amlodipine-treated rats, but not in low-dose amlodipine-treated rats. In comparison to amlodipine treatment, pranidipine treatment significantly reduced myocyte size and central venous pressure. Furthermore, both pranidipine and high-dose amlodipine treatment significantly reduced myocardial protein levels of atrial natriuretic peptide and inducible nitric oxide synthase, whereas pranidipine only significantly decreased tumor necrosis factor-α, and improved sarcoplasmic reticulum Ca2+ATPase2 protein levels. We conclude that pranidipine ameliorates the progression of left ventricular dysfunction and cardiac remodeling in rats with heart failure after autoimmune myocarditis in a lower dose when compared to amlodipine and which may be a clinically potential therapeutic agent for the treatment of heart failure.