Protective Effects of Berberine as A Natural Antioxidant and Anti-Inflammatory Agent Against Nephrotoxicity Induced by Cyclophosphamide in Mice

2021 ◽  
Author(s):  
Mohammad Amin Mombeini ◽  
Hadi Kalantar ◽  
Elahe Sadeghi ◽  
Mehdi Goudarzi ◽  
Hamidreza Khalili ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Serum Levels ◽  
Stress Factors ◽  
Control Group ◽  
Protective Effects ◽  
Group I ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Purpose Cyclophosphamide is an alkylating agent with nephrotoxicity that constraints its clinical application. Berberine is an isoquinoline derivative alkaloid with biological functions like antioxidant and anti-inflammatory. The current research intended to examine the nephroprotective impacts of berberine against cyclophosphamide-stimulated nephrotoxicity. Methods Forty animal subjects were randomly separated into five categories of control (Group I). Cyclophosphamide (200 mg/kg, i.p., on 7th day) (Group II), and groups III and IV that received berberine 50 and 100 mg/kg orally for seven days and a single injection of cyclophosphamide on 7th day. Group V as berberine (100 mg/kg, alone). On day 8, blood samples were drawn from the retro-orbital sinus to determine serum levels of blood urea nitrogen (BUN), creatinine (Cr), Neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) as biomarkers for kidney injury. Nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities as oxidative stress factors, tumor necrosis factor- α (TNF-α) and interleukin 1 beta (IL-1β) levels as inflammatory mediators were assessed in kidney tissue. Results The results of this study demonstrated that berberine was able to protect remarkably the kidney from CP-induced injury through decreasing the level of BUN, Cr, NGAL, KIM-1, NO, MDA TNF-α, IL-1β and increasing the level of GSH, CAT, SOD and GPx activities. Conclusion Berberine may be employed as a natural agent to prevent cyclophosphamide-induced nephrotoxicity through anti-oxidant and anti-inflammatory effects.

scholarly journals Anti-Oxidant and Anti-Inflammatory Effects of Lipopolysaccharide from Rhodobacter sphaeroides against Ethanol-Induced Liver and Kidney Toxicity in Experimental Rats

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7437
Author(s):  
Eman T. Mehanna ◽  
Al-Shimaa A. Ali ◽  
Fatma El-Shaarawy ◽  
Noha M. Mesbah ◽  
Dina M. Abo-Elmatty ◽  
...  
Keyword(s):  
Rhodobacter Sphaeroides ◽  
Iron Homeostasis ◽  
Kidney Injury ◽  
Control Group ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Hepcidin Expression ◽  
Tnf Α ◽  
Anti Oxidant ◽  
Anti Inflammatory

This study aimed to investigate the protective effects of lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) against ethanol-induced hepatotoxicity and nephrotoxicity in experimental rats. The study involved an intact control group, LPS-RS group, two groups were given ethanol (3 and 5 g/kg/day) for 28 days, and two other groups (LPS-RS + 3 g/kg ethanol) and (LPS-RS + 5 g/kg ethanol) received a daily dose of LPS-RS (800 μg/kg) before ethanol. Ethanol significantly increased the expression of nuclear factor kappa B (NF-κB) and levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the liver tissue and decreased anti-oxidant enzymes. Hepcidin expression was downregulated in the liver, with increased serum levels of ferritin and iron. Prior-administration of LPS-RS alleviated the increase in oxidative stress and inflammatory markers, and preserved iron homeostasis markers. In the kidney, administration of ethanol caused significant increase in the expression of NF-κB and the levels of TNF-α and kidney injury markers; whereas LPS-RS + ethanol groups had significantly lower levels of those parameters. In conclusion; this study reports anti-oxidant, anti-inflammatory and iron homeostasis regulatory effects of the toll-like receptor 4 (TLR4) antagonist LPS-RS against ethanol induced toxicity in both the liver and the kidney of experimental rats.

scholarly journals Protective Effects of Hydroalcoholic Extract of Rosa canina Fruit on Vancomycin-Induced Nephrotoxicity in Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Hossein Sadeghi ◽  
Ehsan Karimizadeh ◽  
Heibatollah Sadeghi ◽  
Esmaeel Panahi kokhdan ◽  
Mahboubeh Mansourian ◽  
...  
Keyword(s):  
Kidney Tissue ◽  
Serum Levels ◽  
Treated Group ◽  
Protein Carbonyl ◽  
Control Group ◽  
Histopathological Analysis ◽  
Protective Effects ◽  
Rosa Canina ◽  
Ms Analysis ◽  
Group I

Vancomycin-induced nephrotoxicity (VIN) has been reported to occur in 5–35% of recipient patients. The aims of the study were to evaluate protective effects of Rosa canina (RC) on VIN in rats. Rats were randomly divided into five groups as follows: control group I, group II (received VAN 400 mg/kg/day, every 12 h at doses of 200 mg/kg/day, for 7 consecutive days), group III (VAN + RC 250 mg/kg/day, for 7 consecutive days), group IV (VAN + RC 500 mg/kg/day, for consecutive days), and group V (received RC 500 mg/kg/day, for consecutive 7 days). On the eighth day after anesthetizing the animals, blood samples were taken from the heart, and then, the kidneys were removed to investigate kidney function, oxidative stress, and histopathological marker. Also, the chemical composition of RC extract was identified by GC-MS analysis. Oral dose of 500 mg/kg RC extract significantly reduced the serum levels of blood urea nitrogen (BUN), creatinine (Cr), malondialdehyde (MDA), and nitric oxide (NO) and also the kidney tissue MDA, protein carbonyl, and NO metabolites (nitrite) levels compared to the VAN-treated group ( P < 0.05 ). Based on histopathological analysis, RC extract at the dose of 500 mg/kg inhibited the destructive effects of VAN on kidney tissues. GC-MS analysis indicated that the main compositions were found to be lactose (21.96%), 3-t-butyloxaziridine (20.91%), and 5-oxymethylfurfurole (16.75%). The results indicated that oral administration of RC was able to reduce VAN-induced nephrotoxicity in rats, possibly through antioxidant pathways.

scholarly journals Intraperitoneal Administration of Rosuvastatin Prevents Postoperative Peritoneal Adhesions by Decreasing the Release of Tumor Necrosis Factor

2018 ◽  
Vol 91 (1) ◽  
pp. 79-84 ◽  
Author(s):  
Stefan Chiorescu ◽  
Octavian Aurel Andercou ◽  
Nicolae Ovidiu Grad ◽  
Ion Aurel Mironiuc
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Intraperitoneal Administration ◽  
Serum Levels ◽  
Control Group ◽  
Peritoneal Adhesions ◽  
Group I ◽  
Anti Inflammatory ◽  
Necrosis Factor

Objectives. The purpose of this experimental study was to demonstrate the reduction of peritoneal adhesions formation in rats after intraperitoneal administration of rosuvastatin, due to its anti-inflammatory effect.Method. Peritoneal adhesions were induced in 120 Wistar-Bratislava rats divided into 4 groups (n=30), using a parietal and visceral (cecal) abrasion model. Group I was designated as control group; in group II, a saline solution was administered intraperitoneally; in groups III and IV, a single dose of rosuvastatin solution, 10 mg/kg and 5 mg/kg respectively, was injected intraperitoneally. The serum values of tumor necrosis factor (TNF-α) and interleukin-1 (IL-1α) were determined on day 1 and day 7 postoperatively (ELISA). Macroscopic assessment of the peritoneal adhesions was conducted on day 14.Results. Rosuvastatin therapy induced a significant decrease of tumor necrosis factor serum levels in groups III and IV, on day 1 and day 7 (p<0.01). Intraperitoneal administration of rosuvastatin correlated with a decrease of mean interleukin-1α levels on postoperative day 1 in groups III (p=0.0013) and IV (p=0.00011), but not on day 7, where the differences were no longer statistically significant (p=0.8) The reduction of postoperative peritoneal adhesions in the experimental rat model is supported by the anti-inflammatory effect of rosuvastatin, mediated mainly by the tumor necrosis factor.Conclusions. Rosuvastatin prevents the formation of postoperative peritoneal adhesions in rats. This effect may be linked to the inhibition of proinflammatory cytokines release in the early stages of adhesions formation. The present study suggests that rosuvastatin may be an efficient pharmacological agent in the prevention of postoperative peritoneal adhesions development, and requires further studies as it has a promising application value.

scholarly journals A Randomized Control Trial Study to Determine the Effect of Melatonin on Serum Levels of IL-1β and TNF-α in Patients with Multiple Sclerosis

2020 ◽  
Author(s):  
Masoomeh Yosefifard ◽  
Gholamhassan Vaezi ◽  
Ali Akbar Malekirad ◽  
Fardin Faraji ◽  
Vida Hojati
Keyword(s):  
Multiple Sclerosis ◽  
Interleukin 1 ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Treatment Groups ◽  
Tnf Α ◽  
Significant Difference ◽  
The Central Nervous System

Multiple sclerosis (MS) is the most common neurological disease that happens at a young age. MS is an inflammatory disease; associated with the demyelination of the central nervous system. Therefore, some inflammatory factors are effective in the mechanism and progression of the disease. Melatonin, as a multi-effect substance including anti-inflammatory effects, can reduce symptoms of MS in patients with a change in their inflammatory factors level. In this study, 50 MS patients who were referred to the MS Society of Markazi Province were randomly selected. All patients were treated with routine MS treatment (interferon) and were divided into control (25 placebo recipients) and treatment (25 recipients of 3 mg melatonin per day for 24 weeks) groups. Anthropometric data of patients including height, weight, and age were determined. Blood samples were collected after fasting in order to determine serum levels of interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Then, samples were immediately centrifuged for serum separation and sera were transferred to a freezer at -80°C and serum levels of these factors were determined; using ELISA kit. The results of this study showed that there was no significant difference between the control and treatment groups in terms of serum levels of TNF-α. However, the level of IL-1β was significantly reduced in the treatment group compared to the control group, indicating that melatonin decreases this inflammatory substance. Our findings suggest a valuable strategy in the treatment of patients who suffer from MS

scholarly journals The Effect of Superoxide Dismutase on Inhibition of Acute Kidney Injury Induced by Sepsis Based on Kidney Tissue Histology and Murine Sepsis Score

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Jufitriani Ismy ◽  
Maimun Syukri ◽  
Dessy R. Emril ◽  
Nanan Sekarwana ◽  
Jufriady Ismy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Superoxide Dismutase ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Male Rats ◽  
Control Group ◽  
Control Group Design ◽  
Group I ◽  
Sepsis Score

Sepsis is one of the leading causes contributing to the incidence of acute kidney injury (AKI). Oxidative stress can be used as the main approach against sepsis-induced AKI. One of the primary antioxidants that plays a role in warding off oxidative stress is superoxide dismutase (SOD). This research aimed to observe the effect of antioxidant SOD in inhibiting sepsis in AKI based on kidney tissue histopathology. The research method was an experimental laboratory with a post-test-only control group design. Twenty-five adult male rats aged 12–16 weeks, weighing between 200 and 250 g, were randomly divided into five groups: Group I, as a positive control, where rats were injected with lipopolysaccharides (LPS); Group II, as a negative control; Group III, as treatment 1, where rats were injected with LPS and administered orally with SOD (Glisodin®) 250 IU daily; Group IV, as treatment 2, where rats were injected with LPS and administered orally with SOD (Glisodin®) 500 IU daily; and Group V, as treatment 2, where rats were injected with LPS and administered orally with SOD (Glisodin®) 1000 IU daily. Rats were administered with SOD (Glisodin®) by oral gavage with a flexible feeding tube for 16 weeks, given once daily in the morning, and then injected with LPS of 10 mg/kg body weight. Glisodin SOD had a significant effect on murine sepsis score (MSS). MSS influenced the tubular injury score linearly. We conclude that the optimal dose of SOD at 1000 IU for inhibiting sepsis-induced AKI incidence is compared to SOD at a dose of 250 and 500 IU. The antioxidant effect of SOD can prevent sepsis-induced AKI with oxidative stress events.

scholarly journals Antioxidant and Anti-Inflammatory Effects of Curcumin Nanoparticles on Drug-Induced Acute Myocardial Infarction in Diabetic Rats

Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 504 ◽  
Author(s):  
Boarescu ◽  
Boarescu ◽  
Bocșan ◽  
Gheban ◽  
Bulboacă ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Creatine Kinase ◽  
Serum Levels ◽  
Control Group ◽  
Protective Effects ◽  
Curcumin Nanoparticles ◽  
Creatine Kinase Mb ◽  
Anti Inflammatory

We have investigated the cardio-protective effects of pretreatment with curcumin nanoparticles (CUN) compared to conventional curcumin (CUS) on the changes in oxidative stress parameters and inflammatory cytokine levels during induced acute myocardial infarction (AMI) in rats with diabetes mellitus (DM). DM was induced with streptozotocin, and AMI with isoproterenol. Eight groups of seven Wister Bratislava rats were included in the study. The N-C was the normal control group, AMI-C was the group with AMI, DM-C was the group with DM, and DM-AMI-C was the group with DM and AMI. All four groups received saline solution orally during the whole experiment. S-DM-CUS-AMI and S-DM-CUN-AMI groups received saline for seven days prior to DM induction and continued with CUS (200 mg/kg bw, bw = body weight) for S-DM-CUS-AMI and CUN for S-DM-CUN-AMI (200 mg/kg bw) for 15 days before AMI induction. The CUS-DM-CUS-AMI group received CUS (200 mg/kg bw), while the CUN-DM-CUN-AMI received CUN (200 mg/kg bw) for seven days prior to DM induction, and both groups continued with administration in the same doses for 15 days before AMI induction. CUS and CUN prevented elevation of creatine kinase, creatine kinase-MB, lactate dehydrogenase in all groups, with better results in the CUN (S-DM-CUN-AMI and CUN-DM-CUN-AMI groups). CUS and CUN significantly reduced serum levels of oxidative stress markers (malondialdehyde, the indirect assessment of nitric oxide synthesis, and total oxidative status) and enhanced antioxidative markers (total antioxidative capacity and thiols, up to 2.5 times). All groups that received CUS or CUN showed significantly lower serum levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-1β. The best antioxidative and anti-inflammatory effects were obtained for the group that received CUN before DM induction (CUN-DM-CUN-AMI group). Pretreatment with CUN proved higher cardio-protective effects exerting an important antioxidative and anti-inflammatory impact in the case of AMI in DM.

Protective effects of saffron (its active constituent, crocin) on nephropathy in streptozotocin-induced diabetic rats

2014 ◽  
Vol 34 (2) ◽  
pp. 127-134 ◽  
Author(s):  
E Altinoz ◽  
Z Oner ◽  
H Elbe ◽  
Y Cigremis ◽  
Y Turkoz
Keyword(s):  
Plasma Levels ◽  
Heart Defects ◽  
Ischemia Reperfusion ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Diabetic Rats ◽  
Control Group ◽  
Protective Effects ◽  
Active Constituent ◽  
Hydropic Degeneration

The reactive oxygen species take role in pathogenesis of many diseases including hypoxia, hypercholesterolemia, atherosclerosis, nephropathy, hypertension, ischemia–reperfusion damage, and heart defects. The aim of this study was to evaluate whether crocin administration could protect kidney injury from oxidative stress in streptozotocin-induced diabetic rats. The rats were randomly divided into 3 groups each containing 10 animals as follows: group 1, control group; group 2, diabetes mellitus (DM) group; and group 3, DM + crocin group. At the end of the study, trunk blood was collected to determine the plasma levels of blood urea nitrogen (BUN) and creatinine (Cr). The kidney tissue was removed, and biochemical and histological changes were examined. Diabetes caused a significant increase in malondialdehyde (MDA) and xanthine oxidase (XO) activities and a decrease in glutathione (GSH) contents (  p < 0.01) when compared with control group in the rat kidneys. Crocin given to DM rats significantly decreased MDA (  p < 0.01) and XO (  p < 0.05) activities and elevated GSH (  p < 0.05) contents when compared with DM group. Plasma levels of BUN and Cr were significantly higher in the DM group when compared with the control group (  p < 0.01). Pretreatment of the DM animals with crocin decreased the high level of serum Cr and BUN. Control group was normal in histological appearance, but congestion, severe inflammation, tubular desquamation, tubular necrosis, and hydropic degeneration in tubular cells were observed in the DM group. Histopathological changes markedly reduced, and appearance of kidney was nearly similar to control group in DM + crocin group. Our results show that crocin could be beneficial in reducing diabetes-induced renal injury.

The protective effect of chrysin against carbon tetrachloride-induced kidney and liver tissue damage in rats

2020 ◽  
pp. 1-12 ◽  
Author(s):  
Burcu Gul Baykalir ◽  
Aslihan Sur Arslan ◽  
Seda Iflazoglu Mutlu ◽  
Tuba Parlak Ak ◽  
Ismail Seven ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Group Treatment ◽  
Histopathological Examination ◽  
Kidney Tissue ◽  
Control Group ◽  
Protective Effects ◽  
Sod Activity ◽  
Tnf Α ◽  
Liver And Kidney ◽  
Factor Α

Abstract: The aim of this study was to investigate the possible protective effects of chrysin on oxidative status and histological alterations against carbon tetrachloride (CCl4)-induced liver and kidney tissue in rats. The animals were randomly divided into four groups; the control, chrysin (100 mg/kg), CCl4 (0.5 ml/kg) and chrysin + CCl4 groups. Liver and kidney injuries were assessed by biochemical and histopathological examinations. The levels of malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) activity were measured in tissues. Serum tumor necrosis factor-α (TNF-α), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine levels were also measured in blood samples. MDA, serum TNF-α, AST, ALT, urea, and creatinine levels (p < 0.05) were significantly higher, and SOD activity and GSH level were significantly (p < 0.05) lower in the CCl4 group than in the control group. Treatment with chrysin in the chrysin + CCl4 group decreased MDA, AST, ALT, creatinine, and TNF-α levels (p < 0.05), and increased SOD activity, GSH levels (p < 0.05), and serum TNF-α levels (p < 0.05). In addition, body weight change (BWC) (p < 0.05) and feed intake (FI) were significantly lower (p < 0.001) in the CCl4 group than in the control group. Moreover, treatment with chrysin increased BWC and FI in the chrysin + CCl4 group compared with that in the CCl4 group. These findings also confirmed by histopathological examination. The chrysin treatment ameliorated the CCl4-induced biochemical and pathological alterations. These results demonstrated that chrysin provided amelioration on the rat liver and kidney tissues CCl4-induced injury by increasing the antioxidant activity.

Evaluation of Anti-inflammatory and Antioxidant Effects of Sumatriptan on Carbon Tetrachloride-induced Hepatotoxicity in Rats

Drug Research ◽  
2021 ◽  
Author(s):  
Ahmad Reza Dehpour ◽  
Hasan Yousefi-Manesh ◽  
Mohammad Sheibani ◽  
Mohammad Amin Sadeghi ◽  
Sara Hemmati ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Histopathological Examination ◽  
Serum Levels ◽  
Control Group ◽  
Adult Rats ◽  
Toxic Agents ◽  
Tnf Α ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Pre Treatment

AbstractThe liver detoxifies and metabolizes many drugs and xenobiotics which may cause hepatotoxicity due to some toxic agents. Carbon tetrachloride (CCl4) is metabolized in cytochrome P450 and its reactive radical metabolites cause lipid peroxidation, cellular injury, and apoptosis. Sumatriptan (SUM), 5-HT1B/1D receptor agonist, had anti-inflammatory and anti-oxidant effects. In this research the effect of SUM pre-treatment against CCl4-induced hepatotoxicity was examined. Adult rats received SUM (0.1, 0.3 and 1 mg/kg; i.p.) for 3 consecutive days before CCl4 (2 ml/kg; i.p. on the 3rd day). The aminotransferases serum levels, tissue levels of anti-oxidant and pro-inflammatory markers and histopathological examination were evaluated. SUM (0.3 mg/kg) prevented significantly the elevation of aminotransferases versus the control group (CCl4 group) (P<0.0001) and also, reversed meaningfully the changes of the MPO, MDA, SOD and CAT, IL-1β and TNF-α levels. Additionally, CCl4-intoxication resulted to the disruption of lobular and cellular structures and inflammation in histopathological evaluation which is prevented by SUM (0.3 mg/kg). These data revealed that SUM (0.3 mg/kg), but no at doses 0.1 and 1 mg/kg, decreases the hepatotoxicity of induced by CCl4 in rats.

Curcumin Nanomicelle Improves Lipid Profile, Stress Oxidative Factors and Inflammatory Markers in Patients Undergoing Coronary Elective Angioplasty; A Randomized Clinical Trial

2021 ◽  
Vol 21 ◽  
Author(s):  
Bijan Helli ◽  
Hadis Gerami ◽  
Maria Kavianpour ◽  
Habib Heybar ◽  
Seyed Kianoosh Hosseini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Trial ◽  
Lipid Profile ◽  
Inflammatory Markers ◽  
Interleukin 1 ◽  
Stress Factors ◽  
Inflammatory Factors ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Tnf Α

Background: Curcumin demonstrated many pharmacological effects including antioxidants, anti-inflammation, eliminating free radicals, anti-tumor, lipid regulation, and anti-coagulation. Objective: This study aimed to assess and compare curcumin and nano-curcumin effects on lipid profile, oxidative stress, and inflammatory factors related to patients ‘heart. Method: This randomized, double-blind, placebo-controlled clinical trial was conducted on 90 patients undergoing coronary elective angioplasty which were randomly divided into 3 groups. The doses administered for 8 weeks were a 500 mg capsule of curcumin daily for the first group and an 80 mg capsule of nano-curcumin for the second group. However, the placebo group received capsules like curcumin. Lipid profile, oxidative stress factors, and inflammatory markers were measured at the baseline and end of the experiment. Results: Statistically significant changes were observed in the total cholesterol (TC), triacylglycerol (TG) and low-density lipoprotein cholesterol (LDL-C) in the intervention groups to the control group (p<0.05). Curcumin and nano-curcumin supplementation also improved significant changes in plasma levels of total antioxidant capacity (TAC), malondialdehyde (MDA), Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), high-sensitivity C-reactive protein (hs-CRP), Interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in comparison to the placebo (p<0.05). Furthermore, the nano-curcumin group compared to the curcumin group demonstrated significant changes (p<0.05) in TC, TG, SOD, MDA and TNF-α levels. Conclusion: The effects of curcumin on nano formula may be better for cardiac patients due to its high bioavailability.

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