CHILD syndrome: successful treatment of skin lesions with topical lovastatin and cholesterol lotion

Abstract: CHILD syndrome (Congenital Hemidysplasia, Ichthyosiform erythroderma, Limb Defects) is a rare X-linked dominant disease. The authors report a 2-month-old patient presenting with typical features of CHILD syndrome that was treated with a topical solution containing cholesterol and lovastatin, with complete clearance of her CHILD nevus. The changes in skin lipid metabolism that explain the CHILD ichthyosiform nevus and their correction through topical application of cholesterol and lovastatin are discussed.

Sintomas musculares relacionados ao uso de estatinas / Statin-associated muscle symptoms

Nas últimas duas décadas, comprovou-se que a terapia com estatinas é o instrumento isolado mais potente para atenuar o risco cardiovascular, e seu uso frequente foi enfatizado como um dos elementos mais importantes para reduzir a mortalidade cardiovascular nos países desenvolvidos. Uma incidência igualmente frequente de sintomas musculares em usuários de estatinas levanta a possibilidade de um nexo de causalidade, que leva a uma entidade patológica conhecida como sintomas musculares associados a estatinas (SMAS). Estudos e ensaios clínicos mecanicistas destinados a estudar os SMAS levaram a uma definição clara da sua história natural e incidência exata. Essa informação é essencial para evitar riscos desnecessários de formas graves de SMAS. Ao mesmo tempo, essa compreensão concreta dos SMAS evita o diagnóstico exagerado e a suspensão desnecessária de uma das mais poderosas estratégias de prevenção atuais. Nesse contexto, este artigo de revisão reuniu todas as informações disponíveis sobre o assunto, que são apresentadas em detalhe neste documento como a base da identificação e tratamento dos SMAS

In the last 2 decades, statin therapy has proved to be the most potent isolated instrument for attenuating cardiovascular risk, and its frequent use has been highlighted as one of the most important elements for reducing cardiovascular mortality in developed countries. An equally frequent incidence of muscle symptoms in statin users raises the possibility of a causal link, leading to a disease entity known as statin-associated muscle symptoms (SAMS). Mechanistic studies and clinical trials designed to the study of SAMS have led to a clear definition of its natural history and accurate incidence. This information is vital for avoiding unnecessary risk of severe forms of SAMS. At the same time, this concrete understanding of SAMS prevents over-diagnosis and unnecessary suspension of one of the most powerful prevention strategies available today. In this context, this review has gathered all the available information on the issue, which is presented in detail, in this document, as the basis for the identification and management of SAMS

Genome Shuffling of Mangrove Endophytic Aspergillus luchuensis MERV10 for Improving the Cholesterol-Lowering Agent Lovastatin under Solid State Fermentation

In the screening of marine mangrove derived fungi for lovastatin productivity, endophytic Aspergillus luchuensis MERV10 exhibited the highest lovastatin productivity (9.5 mg/gds) in solid state fermentation (SSF) using rice bran. Aspergillus luchuensis MERV10 was used as the parental strain in which to induce genetic variabilities after application of different mixtures as well as doses of mutagens followed by three successive rounds of genome shuffling. Four potent mutants, UN6, UN28, NE11, and NE23, with lovastatin productivity equal to 2.0-, 2.11-, 1.95-, and 2.11-fold higher than the parental strain, respectively, were applied for three rounds of genome shuffling as the initial mutants. Four hereditarily stable recombinants (F3/3, F3/7, F3/9, and F3/13) were obtained with lovastatin productivity equal to 50.8, 57.0, 49.7, and 51.0 mg/gds, respectively. Recombinant strain F3/7 yielded 57.0 mg/gds of lovastatin, which is 6-fold and 2.85-fold higher, respectively, than the initial parental strain and the highest mutants UN28 and NE23. It was therefore selected for the optimization of lovastatin production through improvement of SSF parameters. Lovastatin productivity was increased 32-fold through strain improvement methods, including mutations and three successive rounds of genome shuffling followed by optimizing SSF factors.

Development of a validated liquid chromatography-tandem mass spectrometry assay for the quantification of simvastatin acid, the active metabolite of simvastatin, in human plasma

Simvastatin is a lipid-lowering drug that is metabolized to its active metabolite simvastatin acid (SA). We developed and validated a sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to quantitate SA in human plasma using a liquid-liquid extraction method with methanol. The protonated analytes generated in negative ion mode were monitored by multiple reaction monitoring. Using 500-mL plasma aliquots, SA was quantified in the range of 0.1-100 ng/mL. Calibration was performed by internal standardization with lovastatin acid, and regression curves were generated using a weighting factor of 1/χ2. The linearity, precision, and accuracy of this assay for each compound were validated using quality control samples consisting of mixtures of SA (0.1, 0.5, 5, and 50 ng/mL) and plasma. The intra-batch accuracy was 95.3-107.8%, precision was -2.2% to -3.7%, and linearity (r2) was over 0.998 in the standard calibration range. The chromatographic running time was 3.0 min. This method sensitively and reliably measured SA concentrations in human plasma and was successfully used in clinical pharmacokinetic studies of simvastatin in healthy Korean adult male volunteers.

Anti-atherosclerotic effects of perilla oil in rabbits fed a high-cholesterol diet / 한국실험동물학회지

Anti-atherosclerosis effects of perilla oil were investigated, in comparison with lovastatin, in rabbits fed a high-cholesterol diet (HCD). Hypercholesterolemia was induced in rabbits by feeding the HCD containing 0.5% cholesterol and 1% corn oil, and perilla oil (0.1 or 0.3%) was added to the diet containing 0.5% cholesterol for 10 weeks. HCD greatly increased blood total cholesterol and low-density lipoproteins, and caused thick atheromatous plaques, covering 74% of the aortic wall. Hyper-cholesterolemia also induced lipid accumulation in the liver and kidneys, leading to lipid peroxidation. Perilla oil not only attenuated hypercholesterolemia and atheroma formation, but also reduced fat accumulation and lipid peroxidation in hepatic and renal tissues. The results indicate that perilla oil prevents atherosclerosis and fatty liver by controlling lipid metabolism, and that it could be the first choice oil to improve diet-induced metabolic syndrome.

Inhibition of HMG-CoA reductase by MFS, a purified extract from the fermentation of marine fungus Fusarium solani FG319, and optimization of MFS production using response surface methodology / 中国天然药物

The present study was designed to isolate and characterize a purified extract from Fusarium solani FG319, termed MFS (Metabolite of Fusarium solani FG319) that showed anti-atherosclerosis activity by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Response surface methodology (RSM) was employed to achieve an improved yield from the fermentation medium. The inhibiting effect of the isolate, MFS, on HMG-CoA reductase was greater than that of the positive control, lovastatin. The average recovery of MFS and the relative standard deviation (RSD) ranged between 99.75% to 101.18%, and 0.31% to 0.74%, respectively. The RSDs intra- and inter-assay of the three samples ranged from 0.288% to 2.438%, and from 0.934% to 2.383%, respectively. From the RSM, the concentration of inducer, cultivation time, and culture temperatures had significant effects on the MFS production, with the effect of inducer concentration being more pronounced that other factors. In conclusion, the optimal conditions for the MFS production were achieved using RSM and that MFS could be explored as an anti-atherosclerosis agent based on its ability to inhibit HMG-CoA reductase.

Regulation of lovastatin on a key inflammation-related microRNA in myocardial cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Advances in the understanding of cardiovascular pathogenesis have highlighted that inflammation plays a central role in atherosclerotic coronary heart disease. Therefore, exploring pharmacologically based anti-inflammatory treatments to be used in cardiovascular therapeutics is worthwhile to promote the discovery of novel ways of treating cardiovascular disorders.</p><p><b>METHODS</b>The myocardial cell line H9c2(2-1) was exposed to lipopolysaccharide (LPS) in culture and resulted in a cellular pro-inflammation status. miR-21 microRNA levels were detected using quantitative real-time polymerase chain reaction (Q-RT-PCR). The influence of lovastatin on miR-21 under normal and pro-inflammatory conditions was tested after being added to the cell culture mixture for 24 hours. Conditional gene function of two predicted cardiovascular system relevant downstream targets of miR-21, protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and signal transducer and activator of transcription 3 (STAT3), were analyzed with immunoblotting.</p><p><b>RESULTS</b>Forty-eight hours of LPS treatment significantly increased the miR-21 to 170.71%± 34.32% of control levels (P = 0.002). Co-treatment with lovastatin for 24 hours before harvesting attenuated the up-regulation of miR-21 (P = 0.013). Twenty-four hours of lovastatin exposure up-regulated PPP1R3A to 143.85%± 21.89% of control levels in cardiomyocytes (P = 0.023). Lovastatin up-regulated the phosphorylation level of STAT3 compared to the background LPS pretreatment (P = 0.0077), this effect was significantly (P = 0.018) blunted when miR-21 was functionally inhibited.</p><p><b>CONCLUSIONS</b>miR-21 plays a major role in the regulation of the cellular anti-inflammation effects of lovastatin.</p>

Cholesterol Lowering Effects of Low-dose Statins in Korean Patients

OBJECTIVE: The aim of this study is to compare cholesterol lowering effects of low dose 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in Korean patients. METHODS: A total of 909 consecutive patients were enrolled prospectively according to the criteria of National Cholesterol Education Program guidelines. Lipid profiles were obtained before and 2 months after statin therapy. RESULTS: Atorvastatin 10 mg (n=260), lovastatin 20 mg (n=145), pitavastatin 2 mg (n=80), pravastatin 20 mg (n=28), rosuvastatin 5 mg (n=145), and simvastatin 20 mg (n=208) reduced low density lipoprotein (LDL) cholesterol by -41.8+/-11.0%, -33.8+/-12.8%, -39.3+/-10.8%, -31.5+/-8.9%, -48.8+/-12.3%, and -42.8+/-13.5%, respectively. LDL cholesterol less than 130 mg/dL was achieved in 90.3%, 76.9%, 88.5%, 85.2%, 97.2%, and 94.2%, respectively. The reduction of LDL cholesterol by 30% or more was obtained in 84.4%, 60.7%, 81.6%, 63.0%, 93.0%, and 83.5%, respectively. LDL cholesterol less than 70 mg/dL or the reduction by 50% or more was observed in a small portion of patients and was variable according to the different types of statins. CONCLUSION: A low dose statin was enough to manage dyslipidemia in most Korean patients with low to moderate risks and was even effective in a subpopulation of high risk patients.

Oral Lovastatin Attenuates Airway Inflammation and Mucus Secretion in Ovalbumin-Induced Murine Model of Asthma

PURPOSE: Lovastatin is an effective inhibitor of cholesterol synthesis. A previous study demonstrated that lovastatin can also suppress airway hyperresponsiveness (AHR) in murine model of asthma. We aimed to investigate the effect of lovastatin on mucus secretion and inflammation-associated gene expression in the lungs of murine model of asthma. METHODS: Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) by intraperitoneal injection, and orally administered lovastatin from days 14 to 27 post-injection. Gene expression in lung tissues was analyzed using real-time polymerase chain reaction. AHR and goblet cell hyperplasia were also examined. BEAS-2B human bronchial epithelial cells were used to evaluate the effect of lovastatin on the expression of cell adhesion molecules, chemokines, and proinflammatory cytokines in vitro. RESULTS: We showed that lovastatin inhibits the expression of Th2-associated genes, including eotaxins and adhesion molecules, in the lungs of murine model of asthma. Mucin 5AC expression, eosinophil infiltration and goblet cell hyperplasia were significantly decreased in the lung tissue of murine model of asthma treated with lovastatin. Furthermore, lovastatin inhibited AHR and expression of Th2-associated cytokines in bronchoalveolar lavage fluid. However, a high dose (40 mg/kg) of lovastatin was required to decrease specific IgE to OVA levels in serum, and suppress the expression of Th2-associated cytokines in splenocytes. Activated BEAS-2B cells treated with lovastatin exhibited reduced IL-6, eotaxins (CCL11 and CCL24), and intercellular adhesion molecule-1 protein expression. Consistent with this, lovastatin also suppressed the ability of HL-60 cells to adhere to inflammatory BEAS-2B cells. CONCLUSIONS: These data suggest that lovastatin suppresses mucus secretion and airway inflammation by inhibiting the production of eotaxins and Th2 cytokines in murine model of asthma.

Effects of lovastatin, clomazone and methyl jasmonate treatment on the accumulation of purpurin and mollugin in cell suspension cultures of Rubia cordifolia / 中国天然药物

AIM@#To determine the IPP origin of the naphthoquinones (NQs) in Rubia cordifolia, and to evaluate the effects of methyl jasmonate (MeJA) treatment, MEP, and MVA pathway inhibitor treatment on the accumulation of anthraquinones (AQs) and NQs in cell suspension cultures of R. cordifolia.@*METHODS@#Cell suspension cultures of R. cordifolia were established. Specific inhibitors (lovastatin and clomazone) and MeJA were supplied to the media, respectively. Treated cells were sampled every three days. Content determination of purpurin (AQs) and mollugin (NQs) were carried out using RP-HPLC. The yield of the two compounds was compared with the DMSO-supplied group and the possible mechanism was discussed.@*RESULTS@#Lovastatin treatment increased the yield of purpurin and mollugin significantly. Clomazone treatment resulted in a remarkable decrease of both compounds. In the MeJA-treated cells, the purpurin yield increased, meanwhile, the mollugin yield decreased compared with control.@*CONCLUSION@#The IPP origin of mollugin in R. cordifolia cell suspension cultures was likely from the MEP pathway. To explain the different effects of MeJA on AQs and NQs accumulation, studies on the regulation and expression of the genes, especially after prenylation of 1,4-dihydroxy-2-naphthoic acid should be conducted.

Cytochrome P450 drug interactions with statin therapy

Statins are commonly used in the treatment of hyperlipidaemia. Although the benefits of statins are well-documented, they have the potential to cause myopathy and rhabdomyolysis due to the complex interactions of drugs, comorbidities and genetics. The cytochrome P450 family consists of major enzymes involved in drug metabolism and bioactivation. This article aims to highlight drug interactions involving statins, as well as provide updated recommendations and approaches regarding the safe and appropriate use of statins in the primary care setting.

Cloning and application of a novel hydroxylase in lovastatin conversion / 生物工程学报

Wuxistatin, a novel and potent statin, is converted from lovastatin by Amycolatopsis sp. CGMCC1149. In the bioconversion, lovastatin is firstly hydroxylated by a hydroxylase. To obtain the critical hydroxylase, a novel hydroxylase gene was isolated from Amycolatopsis sp. CGMCC1149 by Degenerate PCR and Self-Formed Adaptor PCR and expressed in Escherichia coli. BLAST sequence analysis revealed that the gene belonged to cytochrome P450 gene superfamily and could encode a 403-amino-acid protein with a molecular weight of 44.8 kDa. The secondary structure prediction result showed that this protein contained many typical functional regions of P450, such as oxygen binding site, ion-pair region and heme binding region. Meanwhile, a catalytic function verification system was constructed by NADH, ferredoxin and ferredoxin reductase which could catalyze lovastatin hydroxylation into the target product. These would be helpful for further studies in large-scale production of wuxistatin.

Lovastatin protects mithochondrial and renal function in kidney ischemia-reperfusion in rats / Lovastatina protege a função renal e mitocondrial na isquemia/reperfusão renal em ratos

PURPOSE: To investigate the effect of lovastatin on renal ischemia followed by reperfusion. METHODS: Thirty one Wistar rats submitted to left renal ischemia for 60 minutes followed by contralateral nephrectomy were divided into two groups: A (n =17, control, no treatment), and B (n=14, lovastatin 15 mg/kg/day p.o. ten days before ischemia). The animals were sacrificed at the end of ischemia, after 24 hours and at seven days after reperfusion. Survival, serum urea and creatinine levels and renal mitochondrial function were evaluated. RESULTS: Mortality was 29.4% in group A and 0.7% in group B. Urea and creatinine levels were increased in both groups, but the values were significantly lower in group B. Mitochondrial function showed decoupling in 83.4% of group A, as opposed to 38.4/% of group B. CONCLUSIONS: The result shows a protective action of renal function by lovastatin administered before ischemia/reperfusion. Since most of the mitochondrial fraction presented membranes with the ability to maintain ATP production in group B, stabilization of the mitochondrial membrane should be considered as part of the protective action of lovastatin on renal function in ischemia/reperfusion.

OBJETIVO: Investigar a ação da lovastatina na isquemia renal seguida de reperfusão. MÉTODOS: Trinta e um ratos Wistar submetidos à isquemia renal esquerda durante 60 minutos, seguida da nefrectomia contralateral, foram distribuídos em dois grupos: A (n=17, controle, sem tratamento) e B (n=14, recebendo 15 mg/Kg/dia de lovastatina via oral), durante os dez dias que antecederam a isquemia. Os animais foram mortos ao final da isquemia, e com 24 horas e sete dias após a reperfusão. Foram avaliadas a sobrevida, os valores séricos de uréia e creatinina e a função mitocondrial renal. RESULTADOS: A mortalidade foi 29,4% no grupo A e 0,7% no grupo B. Os níveis de uréia e creatinina elevaram-se nos dois grupos, mas foram significativamente menores no grupo B. No grupo A a função mitocondrial renal ficou desacoplada em 83,4% dos ensaios, enquanto que no grupo B isto ocorreu em apenas 38,4% dos ensaios. CONCLUSÕES: Os resultados mostram que a administração de lovastatina antes do episódio de isquemia protege a função renal. No grupo B, como a maior parte da fração mitocondrial isolada apresentou função acoplada à produção de ATP, deve-se também considerar a estabilização da membrana mitocondrial como parte da ação protetora da lovastatina na função renal durante isquemia e reperfusão.

Anti-hypercholesterolemic and anti-atherosclerotic effects of polarized-light therapy in rabbits fed a high-cholesterol diet / 한국실험동물학회지

The effects of polarized-light therapy (PLT) on high-cholesterol diet (HCD)-induced hypercholesterolemia and atherosclerosis were investigated in comparison with that of lovastatin in rabbits. Hypercholesterolemia was induced by feeding male New Zealand white rabbits with 1% cholesterol in diet for 2 weeks and maintained with 0.5% cholesterol for 6 weeks, followed by normal diet for 2 weeks for recovery. Lovastatin (0.002% in diet) or daily 5-min or 20-min PLT on the outside surface of ears was started 2 weeks after induction of hypercholesterolemia. Hypercholesterolemic rabbits exhibited great increases in serum cholesterol and low-density lipoproteins (LDL) levels, and finally severe atheromatous plaques formation covering 57.5% of the arterial walls. Lovastatin markedly reduced both the cholesterol and LDL, but the reducing effect (47.5%) on atheroma formation was relatively low. By comparison, 5-min PLT preferentially decreased LDL, rather than cholesterol, and thereby potentially reduced the atheroma area to 42.2%. Notably, 20-min PLT was superior to lovastatin in reducing both the cholesterol and LDL levels as well as the atheromatous plaque formation (26.4%). In contrast to the increases in blood alanine transaminase and aspartate transaminase following lovastatin treatment, PLT did not cause hepatotoxicity. In addition, PLT decreased platelets and hematocrit level. The results indicate that PLT attenuates atherosclerosis not only by lowering blood cholesterol and LDL levels, but also by improving blood flow without adverse effects. Therefore, it is suggested that PLT could be a safe alternative therapy for the improvement of hypercholesterolemia and atherosclerosis.

Effect of Statins on C-reactive Protein, Lipoprotein(a) and Fibrinogen in Hypercholesterolemic Patients

OBJECTIVE: C-reactive protein (CRP), lipoprotein (a)[Lp(a)], and fibrinogen are associated with systemic inflammatory reactions. Statins have anti-inflammatory effects. However, the effect of statins on these parameters is inconsistent. We evaluated the effect of statins on inflammatory markers and variables related to changes in these markers. METHODS: A total of 390 hypercholesterolemic patients were enrolled. Atorvastatin (n=112), lovastatin (n=25), pitavastatin (n=49), rosuvastatin (n=20), and simvastatin (n=184) were administered. Lipids, CRP, Lp(a), and fibrinogen levels were measured before and after 2 months of the therapy. RESULTS: Statins reduced cholesterol, low density lipoprotein (LDL) cholesterol, and triglyceride levels by -28.9+/-9.1% (P=0.000), -41.4+/-12.4% (P=0.000), and -11.6+/-39.4% (P=0.000), respectively and increased high density lipoprotein (HDL) cholesterol level by 2.56+/-13.2% (P=0.014). CRP levels decreased from 1.23+/-1.30 to 1.14+/-1.29 mg/L (P=0.000). Lp(a) levels were not changed (P=0.91) and fibrinogen levels increased from 277.8+/-54.4 to 282.6+/-56.9 mg/dL (P=0.042). Changes in CRP levels were associated with baseline CRP levels (r=-0.56, P=0.000) and changes in HDL cholesterol levels (r=-0.14, P=0.005). Changes in Lp(a) levels were associated with changes in triglyceride (r=-0.24, P=0.000) and baseline aspartate aminotransferase level (r=0.12, P=0.015). Changes in fibrinogen levels were associated with baseline fibrinogen levels (r=-0.40, P=0.000), sex (r=0.18, P=0.001), and changes in HDL cholesterol levels (r=-0.15, P=0.003). CONCLUSION: Inflammatory markers showed different responses to statins and changes in these markers were associated with different parameters. This finding suggests that anti-inflammatory effect of statin is confined to a specific pathway of inflammation.

Estatinas para el síndrome coronario agudo: medicina basada en evidencia sobre la administración temprana con dosis de carga / Stations in acute coronary syndrome: use of an early loading dose

Objetivo: En algunos Servicios de Emergencias de la CCSS, a los pacientes con infarto agudo de miocardio se les administra una dosis alta aunque variables de lovastatina en las primeras horas de evolución de los síndromes coronarios agudos, con la expectativa de lograr efectos pleiotrópicos, un resultado positivo sobre el endotelio y la disminución de mediadores inflamatorios. Analizar la evidencia científica que sustenta el beneficio de esta intervención farmacológica y clarificar la posible dosis oral y el potencial intervalo idóneo. Búsqueda vías electrónicas en sistemas secundarios de información científica y análisis de fuentes primarias, con énfasis en ensayos clínicos aleatorizados que evalúen la eficacia de las estatinas en los eventos coronarios agudos; también de fuentes terciarias , específicamente revisiones sistemáticas y guías de consenso para prácticas clínicas basadas en evidencia y revisiones por instancias evaluadoras de tecnología con reconocimiento internacional. Resultados: Cuatro ensayos clínicos aleatorizados controlados con placebo, no demostraron diferencias significativas ni clínicamente relevantes en la variable primaria combinada: evento cardiaco mayor, muerte, IAM recurrente fatal, AVC fatal u otra causa de muerte cardiovascular, ninguno usó dosis de carga, ni se inició la administración en las 24hs del inicio de la sintomatología. Conclusión: Ante la falta de evidencia que permita proyectar con claridad un papel beneficioso para las estatinas en el manejo inicial del síndrome coronario agudo, esta práctica desequilibra la relación beneficio/riesgo y se aleja de los principios del uso racional de medicamentos y la aplicación del paradigma de la medicina basada en evidencia.

In vivo and in vitro anti-inflammatory and anti-nociceptive activities of lovastatin in rodents

Statins are among the most prescribed drugs in recent clinical practice. They are also known for their pleiotropic actions, which are independent of their lipid-lowering properties. The effect of lovastatin was investigated against carrageenan-induced paw edema in male Wistar rats (200-250 g) and on leukocyte migration, as measured by carrageenan-induced peritonitis in male Swiss mice (20-25 g), which are models of acute inflammation. Lovastatin (administered 1 h prior to carrageenan), at oral doses of 2, 5, and 10 mg/kg, markedly attenuated paw edema formation in rats at the 4th hour after carrageenan injection (25, 43, and 37 percent inhibition, respectively). Inhibitions of 20, 45 and 80 percent were observed in the leukocyte migration, as evaluated by carrageenan-induced peritonitis in mice with lovastatin doses of 0.5, 1 and 5 mg/kg, as compared to controls. Furthermore, lovastatin (administered 1 h before initiation) reduced the nociceptive effect of the formalin test in mice, at both phases, at doses of 2, 5, and 10 mg/kg: first phase (51, 65, and 70 percent, respectively) and second phase (73, 57, and 66 percent inhibition of licking time, respectively). The anti-nociceptive activity of lovastatin was inhibited by naloxone (3 mg/kg, sc). Lovastatin (0.01, 0.1, and 1 µg/mL) inhibited by 23, 79, and 86 percent, respectively, the release of myeloperoxidase from human neutrophils. Leukocyte (predominantly neutrophils) infiltration was almost completely reduced by lovastatin treatment, as observed in the model of acute paw edema with hematoxylin and eosin staining. In addition, lovastatin decreased the number of cells expressing tumor necrosis factor-α (TNF-α) and the inducible form of nitric oxide synthase (iNOS) activity. Therefore, the alterations in leukocyte activity and cytokine release could contribute to the anti-inflammatory activity of lovastatin.

Rhabdomyolysis related to statin and seizures: report of 3 cases / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the clinical features and prognosis of rhabdomyolysis related to seizure attacks and use of statin.</p><p><b>METHODS</b>The medical records of 3 patients with established diagnosis of rhabdomyolysis were analyzed and the related literatures were reviewed.</p><p><b>RESULTS</b>All the 3 patients had seizure attacks and/or used statin before the onset of rhabdomyolysis. Two of the patients complained of back pain, and all the 3 patients had dark-colored urine. Serum levels of creatine kinase (CK) were markedly increased by over 50 times above the normal upper limit. CK level kept increasing even after proper interventions, till reaching the peak level about 3 days later. The patients improved rapidly with full recovery thereafter, and CK became normal in 2 weeks. None of the patients had renal failure.</p><p><b>CONCLUSION</b>Seizure attacks and use of statin are common risk factors for non-traumatic rhabdomyolysis. Caution needs to be taken when prescribing statin to patients with recent seizure attacks. Special attention should be given to such early symptoms as muscle pain, weakness and dark-colored urine, and CK level monitoring is advisable in such cases.</p>

Lovastatin changes activities of lactate dehydrogenase A and B genes in rat myocardial cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Lactate dehydrogenase (LDH) is a crucial regulator of energy metabolism in many organs including the heart. Lovastatin is widely used in prevention and treatment of coronary heart disease and is a drug with substantial metabolic influences. Our study aimed to determine the activities of the lactate dehydrogenase A and B (LDHA and LDHB) genes following lovastatin treatment.</p><p><b>METHODS</b>The rat myocardial cell line H9c2(2-1) in culture was exposed to 100 nmol/L lovastatin for 24 hours or for five days. The functions of the LDHA and LDHB genes were examined at the transcriptional (mRNA) level with quantitative real-time polymerase chain reaction (Q-RT-PCR), and at the translational (protein) level with immunoblotting.</p><p><b>RESULTS</b>When compared with control levels, the LDHA mRNA went up by (151.65 ± 16.72)% (P = 0.0132) after 24 hours and by (175.28 ± 56.54)% (P = 0.0366) after five days of lovastatin treatment. Although 24 hours of lovastatin treatment had no significant effects on LDHB mRNA levels, when the treatment was extended to five days, LDHB mRNA levels were significantly down-regulated to (63.65 ± 15.21)% of control levels (P = 0.0117). After 24 hours of treatment with lovastatin, there were no significant changes in protein levels of either LDHA or LDHB. When treatment time was extended to five days, the protein levels of LDHA were up-regulated by (148.65 ± 11.81)% (P = 0.00969), while the protein levels of LDHB were down-regulated to (64.91 ± 5.47)% of control levels (P = 0.0192).</p><p><b>CONCLUSIONS</b>Lovastatin affects gene activities of LDHA and LDHB differently, which may reveal novel pharmacological effects of lovastatin.</p>

Effect of hydroxymethylglutaryl-CoA reductase inhibitors on low-density lipoprotein cholesterol, interleukin-6, and high-sensitivity C-reactive protein in end-stage renal disease

This study was conducted to determine the effect of statins on the serum levels of interleukin-6 [IL-6], low-density lipoprotein cholesterol [LDLC], and high-sensitivity C-reactive protein [HSCPR]. This randomized clinical trial was carried out on 95 hemodialysis patients divided into three groups of atorvastatin, 10 mg; simvastatin, 20 mg; and lovastatin, 40 mg, daily, administered for 2 months. Levels of serum HSCRP, IL-6, and LDLC were all measured before and after the study period. At baseline, 59% of the hemodialysis patients presented with elevated HSCRP, 46.3% them had increased IL-6, and 26.3% had an increased LDLC level. The three drugs were capable to lower the level of HSCRP, among which atorvastatin had the highest effect size [41.8% reduction, P = .001]. Lovastatin stood in the next [37.6% reduction, P = .02], while HSCRP reduction was not significant in the simvastatin group [25% reduction, P = .14]. Neither of the drugs significantly reduced IL-6 levels. Effects of atorvastatin and simvastatin on the LDLC levels were significant, while lovastatin had a marginal effect. Use of statins resulted in CRP reduction in patients on hemodialysis. Atorvastatin was much more effective than lovastatin, while CRP reduction was not significant by simvastatin. However, simvastatin had the greatest impact on LDLC. None of these drugs could reduce IL-6 levels within 2 months