Degeneration of pyramidal cells of CA1, CA2, and CA3 area of the hippocampus in male rats under the influence of Simvastatin

Background: Simvastatin is a lipophilic statin and can cross the blood-brain barrier. This study aimed to evaluate the Effect of Simvastatin on pyramidal cells in CA1, CA2, and CA3 regions of the hippocampus in healthy male rats. Method: For the experiment, 36 male Wistar rats with an average weight of 300-250 g were divided into six groups (each group comprised six heads). Groups: 1): Control group, 2): Vitamin D dose 5 µg/kg, 3): Simvastatin group dose 1 mg/kg, 4): Simvastatin group dose 10 mg/kg, 5): Simvastatin group dose 1 mg/kg + vitamin D dose 5 µg/kg, 6): Simvastatin group dose 10 mg/kg + vitamin D dose 5 µg/kg. The duration of drug use was 28 days. At the end of the drug administration period, the animals were slaughtered, then blood samples were taken from the animals (to check TC[1] and LDL-C[2]), and finally, the brain tissue of the animals was extracted to prepare microscopic sections. Results: Statistical results of total cholesterol and LDL-C in rat serum showed that the groups receiving simvastatin 10 mg/kg and simvastatin 10 mg/kg with vitamin D supplement 5 µg/kg were significantly different compared to the control group (P <0.05).Statistical results showed a significant increase (P <0.05) in degenerated cells in the groups receiving simvastatin 10 mg/kg and simvastatin 10 mg/kg with vitamin D supplementation compared with the control group in CA1 and CA2 regions. The statistical results of the study of the percentage of The statistical results of the study of the rate of degenerative cells in CA3 area CA3 of the hippocampus showed that all groups except the vitamin D group had a significant difference (P <0.50) in the percentage of degenerative cells in this region compared to the control group.Conclusion: The results of the present study showed that Simvastatin, due to its lipophilic nature, easily crosses the blood-brain barrier and reduces cholesterol in the brain, thus causing the degeneration of pyramidal cells in the hippocampus.[1] Total cholesterol[2] Low-Density Lipoproteins

Degeneration of pyramidal cells of CA1, CA2, and CA3 are of the hippocampus in male rats under the influence of simvastatin

Background: Simvastatin is a lipophilic statin and can cross the blood-brain barrier. The aim of this study was to evaluate the effect of simvastatin on pyramidal cells in CA1, CA2, and CA3 regions of the hippocampus in healthy male rats. Method: For the experiment, 36 male Wistar rats with an average weight of 300-250 g were divided into six groups of six (each group comprised six heads). Groups: 1): Control group, 2): Vitamin D dose 5 µg / kg, 3): Simvastatin group dose 1 mg / kg, 4): Simvastatin group dose 10 mg / kg, 5): Simvastatin group dose 1 mg / kg + vitamin D dose 5 µg / kg, 6): Simvastatin group dose 10 mg / kg + vitamin D dose 5 µg / kg. The duration of drug use was 28 days. At the end of the drug administration period, the animals were slaughtered, then blood samples were taken from the animals (to check TC[1] and LDL-C[2]) and finally the brain tissue of the animals was extracted to prepare microscopic sections. Results: Statistical results of total cholesterol and LDL-C in rat serum showed that the groups receiving simvastatin 10 mg / kg and simvastatin 10 mg / kg with vitamin D supplement 5 µg / kg were significantly different compared to the control group (P <0.05).Statistical results showed a significant increase (P <0.05) in degenerated cells in the groups receiving simvastatin 10 mg / kg and simvastatin 10 mg / kg with vitamin D supplementation compared with the control group in CA1 and CA2 regions. The statistical results of the study of the percentage of The statistical results of the study of the percentage of degenerative cells in CA3 region CA3 of the hippocampus showed that all groups except vitamin D group had a significant difference (P <0.50) in the percentage of degenerative cells in this region compared to the control group.Conclusion: The results of the present study showed that simvastatin, due to its lipophilic nature, easily crosses the blood-brain barrier and reduces cholesterol in the brain, thus causing the degeneration of pyramidal cells in the hippocampus.

Can Simvastatin reduce COPD Exacerbations? A Randomised Double Blind Controlled Study

Several studies have shown that statins have beneficial effects in chronic obstructive pulmonary disease (COPD) regarding lung function decline, rates and severity of exacerbations, hospitalisation and need for mechanical ventilation.We performed a randomised double-blind placebo-controlled single-center trial of simvastatin at a daily dose of 40 mg versus placebo in patients with Global Initiative for COPD criteria II-IV at a tertiary care pulmonology department in Austria. Scheduled treatment duration was 12 months and main outcome parameter was time to first exacerbation.Overall 209 patients were enrolled. In the 105 patients taking simvastatin, time to first exacerbation was significantly longer compared to the 104 patients taking placebo: median 341 versus 140 days, log-rank test p<0.001. Hazard ratio for risk of first exacerbation for the simvastatin group was 0.51 (95% CI 0.34–0.75; p=0.001). Rate of exacerbations was significantly lower with simvastatin: 103 (41%) versus 147 (59%), p=0.003. The annualised exacerbation rate was 1.45 per patient-year in the simvastatin group and 1.9 in the placebo group (IRR 0.77, 95% CI 0.60 to 0.99).We found no effect on quality of life, lung function, 6-minute walk test and high-sensitivity C-reactive protein. More patients dropped out in the simvastatin group compared to the placebo group (39 versus 29).In our single-center RCT, simvastatin at a dose of 40 mg daily significantly prolonged time to first COPD exacerbation and reduced exacerbation rate.

Comparing different types of statins for secondary prevention of cardio-cerebrovascular disease from a national cohort study

Background Statins have been recommended for use in atherosclerotic cardio-cerebrovascular disease (CCVD). The purpose of this study was to investigate the efficacy of five different types of statin in the secondary prevention of CCVD in patients. Methods This study has a retrospective design and utilised data from the Korean National Health Insurance Service-National Health Screening Cohort. Participants aged 40 to 69 years at baseline were categorized into five statin groups (atorvastatin, rosuvastatin, pitavastatin, simvastatin, and pravastatin). The primary composite outcome was defined as recurrence of CCVD or all causes of death. Cox proportional hazard regression models were adopted after stepwise adjustments for confounders to investigate the difference in efficacy among the different statins. Results Of the 755 final study participants (485: atorvastatin, 34: pitavastatin, 8: pravastatin, 96: rosuvastatin, and 132: simvastatin group), 48 patients experienced primary composite outcomes. The median follow-up duration was 12.4 years across all groups. After stepwise adjustments, the hazard ratios (95% confidence intervals) for primary composite outcomes of atorvastatin, pitavastatin, and rosuvastatin groups were 0.956 (0.456–2.005), 1.347 (0.354–5.116), and 0.943 (0.317–2.803), respectively, when compared with the simvastatin group. Conclusions There were no significant differences between the statins in their efficacy for preventing recurrence of CCVD events and/or death in CCVD patients. However, further large-scale clinical trials are required to confirm these results.

Efficacy and Safety of Berberine Alone or Combined with Statins for the Treatment of Hyperlipidemia: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

To systematically evaluate the efficacy and safety of berberine for the treatment of hyperlipidemia, six electronic literature databases including SinoMed, CNKI, WanFang Data, PubMed, Embase and The Cochrane Library were searched to collect clinical randomized controlled trials (RCTs) of berberine alone or combined with statins for the treatment of hyperlipidemia from the inception to 8 March 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included RCTs. Then, meta-analysis was performed by using RevMan 5.3 software. A total of 11 RCTs involving 1386 patients were finally included. The results of meta-analysis showed that compared with the placebo group, berberine could significantly reduce the total cholesterol and low-density lipoprotein levels and elevate the high density lipoprotein level ([Formula: see text]). Compared with the simvastatin group, berberine was effective only in reducing the level of triglyceride ([Formula: see text], 95% CI: [Formula: see text]0.66, [Formula: see text]0.07, [Formula: see text]). There, however, was no statistical significance between the BBR group and simvastatin group in the low density lipoprotein and high density lipoprotein levels. Compared with the simvastatin group, berberine plus simvastatin was more effective in reducing the level of triglyceride ([Formula: see text], 95% CI: [Formula: see text]0.46, [Formula: see text]0.20, [Formula: see text]) and total cholesterol ([Formula: see text], 95% CI: [Formula: see text]0.60, [Formula: see text]0.12, [Formula: see text]). In terms of adverse reactions, the incidence of adverse reactions including transaminase elevation and muscle aches was lower in the berberine alone or combined with simvastatin group than that in the control group, while the instance of constipation was higher. This study suggests that berberine is effective for hyperlipidemia. The quality and quantity of included studies, however, were dissatisfactory, which might decrease the reliability of the results. Higher quality studies are needed to provide more high quality evidence.

Statin and anemia in chronic kidney disease (CKD): an experimental study

Anemia is a common feature of chronic kidney disease (CKD). The current management of patients with anemia in CKD is controversial. These make anemia is one of the leading causes poor outcome in CKD patients. Our study focus to assess the effect of statin on hemoglobin level with an experimental model of CKD. We perform the animal model of CKD by subtotal nephrectomy procedure. A total of 20 male swiss was used in these study. All the animal divided into 4 groups: sham group (S), nephrectomy (Nx), simvastatin group 5 mg/kgBB (SV5), and simvastatin group 10 mg/kgBB (SV10). Hematological parameters (hemoglobin (Hb), white blood cells (WBC), red blood cell (RBC), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC)), and serum creatinine are measured at the end of the study. The hemoglobin levels in the Ux group decreased significantly compared with the S group (11.02 ± 0.46 vs 14.3 ± 0.15, p<0.0001). While in the SV group, statin administration led to an increase in hemoglobin levels compared with the Ux group but not statistically significant (SV5: 13.26±0.34; Sv10: 12.68±0.26). These results suggest that administration of statins in CKD may improve the condition of anemia by an unknown mechanism, while still requiring other treatment options to maximize the effect of therapy.

Comparison between Effectiveness of Pomegranate Juice (Punica granatum) and Simvastatin for Lowering Blood LDL Level in Hypercholesterolemic Male Rats (Rattus novergicus)

Background: Coronary heart disease (CHD) is one of the leading causes of death in developed and developing countries. In Indonesia 26% of death is caused by CHD. Hypercholesterolemia is one of the risk factors for CHD. Simvastatin is a hypolipidemic drug which has a significant number of side effects such as myopathy. While, Pomegranate juice (Punica granatum) contains anthocyanin, cathechins, tanin, vitamin C and vitamine E which have beneficial effects to decrease blood LDL level. Objective: The aim of this study was to compare the effectiveness of pomegranate juice (Punica granatum) and simvastatin in lowering blood LDL level of hypercholesterolemic male rats (Rattus novergicus).Methodology: This experimental study was executed following by pre and post control group design. This study used 15 male Wistar rats that were divided into three groups as 2% DMSO, simvastatin and pomegranate juice. Blood LDL level was examined at day-0 and day-15 of trial period. Result: Dependent T-test reveals that both pomegranate juice and simvastatin group showed significant difference in lowering blood LDL level before and after treatment. The result of Kruskal Wallis test showed that both pomegranate juice and simvastatin group have more significant efficacy than 2% DMSO. On the other hand, there was no significant difference between effectiveness of pomegranate juice and simvastatin group. Conclusion: Both Pomegranate juice and simvastatin are effective in lowering blood LDL level of hypercholesterolemia male rats and there is no significant difference between effectiveness of pomegranate juice and simvastatin.Bangladesh Journal of Medical Science Vol.15(2) 2016 p.216-219

Local Administration of Simvastatin Stimulates Healing of an Avascular Meniscus in a Rabbit Model of a Meniscal Defect

Background: Repair of an avascular meniscus is challenging because of its low capacity for healing. Several reports have shown that simvastatin stimulates the anabolic activity of intervertebral fibrochondrocytes, suggesting that simvastatin may be used for the treatment of meniscal defects. Purpose: To test whether the local administration of simvastatin stimulates healing of an avascular meniscus in rabbits. Study Design: Controlled laboratory study. Methods: In 30 Japanese White rabbits, a cylindrical defect (1.5-mm diameter) was introduced into the avascular zone of the anterior part of the medial meniscus in bilateral knees. Either a gelatin hydrogel (control group) or simvastatin-conjugated gelatin hydrogel (simvastatin group) was implanted into the defect. Histological assessments were performed using qualitative scoring systems, and immunohistochemical analysis was performed at 12 weeks after surgery. The occupation ratio (OR) and safranin O staining occupation ratio (SOR) were evaluated quantitatively at each time point. Stiffness of the regenerated tissue was analyzed biomechanically at 12 weeks after surgery. Rabbit meniscal cells were cultured in the presence or absence of 0.5 μM simvastatin, and then real-time polymerase chain reaction was performed to evaluate gene expression. Results: The qualitative score was significantly higher in the simvastatin group after 8 and 12 weeks ( P = .031 and .035, respectively). The mean OR and SOR were also significantly higher in the simvastatin group (OR at 8 weeks: 0.396 ± 0.019 [control] vs 0.564 ± 0.123 [simvastatin], P = .008; OR at 12 weeks: 0.451 ± 0.864 [control] vs 0.864 ± 0.035 [simvastatin], P = .001; SOR at 8 weeks: 0.071 ± 0.211 [control] vs 0.487 ± 0.430 [simvastatin], P = .009; SOR at 12 weeks: 0.093 ± 0.088 [control] vs 0.821 ± 0.051 [simvastatin], P = .006). Immunohistochemical analysis showed that at 12 weeks, the reparative tissue was more strongly positive for type I collagen (COL1), type II collagen (COL2), bone morphogenetic protein 2 (BMP-2), and BMP-7 in the simvastatin group than in the control group. Biomechanical analysis showed significantly higher stiffness in the simvastatin group (2.417 ± 1.593 N/ms [control] vs 5.172 ± 1.078 N/ms [simvastatin]; P = .005). In rabbit meniscal cells, BMP-2 and BMP-7 were upregulated after 4 and 8 hours and after 7 and 14 days, whereas COL1A1 and COL2A1 were significantly upregulated by simvastatin after 7 and 14 days. Conclusion: The local administration of simvastatin promotes the regeneration of an avascular meniscus in the rabbit model of a meniscal defect. The mechanism may involve the upregulation of BMPs and the subsequent upregulation of COL1 and COL2. Clinical Relevance: This study suggests that simvastatin stimulated intrinsic healing of an avascular meniscus. The local administration of simvastatin is safe and inexpensive and seems to be a promising treatment of meniscal injuries.

The Effects of Simvastatin on Proteinuria and Renal Function in Patients with Chronic Kidney Disease

Current data suggests that statins might have beneficial effects on renal outcomes. Beneficial effects of statin treatment on renal progression in advanced chronic kidney disease (CKD) are obviously controversial. In a retrospective, controlled study, the authors have evaluated the effects of 53-week treatment with simvastatin, versus no treatment on proteinuria and renal function among 51 patients with CKD stages III-IV. By the end of the 53-week treatment, urine protein excretion decreased from 0.96 (IQR 0.54, 2.9) to 0.48 (IQR 0.18, 0.79) g/g creatinine (P<0.001) in patients treated with simvastatin in addition to ACEI and ARBs, while no change was observed among the untreated patients. Moreover, a significantly greater decrease in urine protein excretion was observed in the simvastatin group as compared with the untreated group. The mean changes of serum creatinine and eGFR did not significantly differ in both groups. A significantly greater decrease in total cholesterol and LDL-cholesterol was found in the simvastatin group than in the untreated group. In summary, apart from lipid lowering among CKD patients, ingesting simvastatin was associated with a decrease in proteinuria. These statin effects may become important for supportive therapy in renal damage in the future.

Abstract 240: Effect of Co-Administration of Simvastatin and Pioglitazone on Lipid Profile and Insulin Resistance in Insulin-Resistant Rats

Objective: Insulin resistance is characterized by hyperglycemia, dyslipidemia, hyperinsulinemia and hypertension. Also, in obesity, decreased plasma adiponectin and increased free fatty acids, are the main factors that correlate with insulin resistance. Thiazolidinediones, like pioglitazone are used to improve insulin sensitivity and ATPIII guidelines suggest statin therapy for correction of dyslipidemia in metabolic syndrome. In this study we evaluated co-administration of simvastatin and pioglitazone on insulin resistance in rats. Materials and Methods: Rats were randomly divided into five groups. After 6 weeks on a high-fructose diet, one group received simvastatin, one group received pioglitazone, and one received pioglitazone and simvastatin. After 2 weeks of treatment, animals were anesthetized with ether. Blood was collected from their heart. Liver, visceral adipose, and muscle tissues were collected and were immediately frozen. Serum glucose, TGs, cholesterol, insulin, adiponectin, and free fatty acids were measured. Expression of PPAR.γ and GLUT4 genes was checked by real-time PCR and Western blotting. Results: Only the results that showed a significant difference are shown. Blood glucose: pioglitazone group (129.1±5.8mg/dl), simvastatin-pioglitazone treated group (137.1±9.9 mg/dl); TG: simvastatin group (123.6±16.6 mg/dl), simvastatin-pioglitazone group (101.5±7.5 mg/dl); Insulin: pioglitazone group (40.27±2.75 p mol/l), simvastatin group (70.07±10.35 pmol/l), simvastatin-pioglitazone (47.62±2.8 pmol/l); Adiponectin: pioglitazone (5.90±0.29 μg/ml), simvastatin-pioglitazone (5.89±0.41μg/ml); HOMA-IR: pioglitazone (2.11±0.13), simvastatin (4.76±0.37), simvastatin-pioglitazone (2.70±0.29). In pioglitazone group, PPAR.γ expression at both mRNA and protein levels was significantly different from insulin resistant group. Conclusion: As the results show, simvastatin has beneficial effects on insulin resistance in rats. Pioglitazone did not show any synergistic effect with simvastatin, however, when used in combination with simvastatin, pioglitazone shows a synergistic effects in lowering TG and HOMAIR that potentially can lower diabetes complications.