Effect of Berberine Plus Bezafibrate Administration on the Lipid Profile of Patients with Mixed Dyslipidemia: A Pilot Clinical Trial.

To evaluate the effect of berberine (BBR) plus bezafibrate administration on the lipid profile of patients with mixed dyslipidemia. A double-blind randomized pilot clinical trial with parallel groups was carried out in 36 patients, aged 30-60 years with mixed dyslipidemia [triglycerides (TG) ≥1.7 mM and total cholesterol (TC) ≥5.2 mM]. Patients were assigned to 3 groups of 12 patients each, receiving oral administration during 90 days of BBR 500 mg t.i.d., bezafibrate 400 mg b.i.d., or BBR 500 mg t.i.d. plus bezafibrate 400 mg b.i.d, respectively. Clinical evaluation, lipid profile, glucose, creatinine, and uric acid levels were measured before and after the pharmacological intervention. Kruskal-Wallis, Wilcoxon, Mann-Whitney U, and χ2 tests were used for statistical analyses; a P ≤ .05 was considered statistically significant. BBR reduced TC levels. Bezafibrate decreased TG, TC, low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein (VLDL) concentrations. BBR plus bezafibrate decreased TG (2.6 ± 0.8 vs. 1.3 ± 0.7 mM, P = .007), TC (6.3 ± 0.7 vs. 4.6 ± 1.2 mM, P = .005), LDL-C (3.4 ± 0.6 vs. 2.2 ± 1.3 mM, P = .037), and VLDL (0.5 ± 0.2 vs. 0.2 ± 0.1 mM, P = .007) levels. Bezafibrate and BBR plus bezafibrate significantly decreased TG, TC, LDL-C, and VLDL concentrations, and thus, remitting the diagnosis of mixed dyslipidemia in 90% of the patients.

Bezafibrate In Vivo Administration Prevents 3-Methylglutaric Acid-Induced Impairment of Redox Status, Mitochondrial Biogenesis, and Neural Injury in Brain of Developing Rats.

3-Methylglutaric acid (MGA) is an organic acid that accumulates in 3-methylglutaconic (MGTA) and 3-hydroxy-3-methylglutaric (HMGA) acidurias. Patients affected by these disorders present with neurological dysfunction that usually appears in the first years of life. In order to elucidate the pathomechanisms underlying the brain injury in these disorders, we evaluated the effects of MGA administration on redox homeostasis, mitochondrial respiratory chain activity, and biogenesis in the cerebral cortex of developing rats. Neural damage markers and signaling pathways involved in cell survival, and death were also measured after MGA administration. Furthermore, since the treatment for MGTA and HMGA is still limited, we tested whether a pre-treatment with the pan-peroxisome proliferator-activated receptor (PPAR) agonist bezafibrate could prevent the alterations caused by MGA. MGA provoked lipid peroxidation, increased heme oxygenase-1 content, and altered the activities of antioxidant enzymes, strongly suggestive of oxidative stress. MGA also impaired mitochondrial function and biogenesis by decreasing the activities of succinate dehydrogenase and various respiratory chain complexes, as well as the nuclear levels of PGC-1α and NT-PGC-1α, and cell content of Sirt1. AMPKα1 was further increased by MGA. Neural cell damage was also observed following the MGA administration, as verified by decreased Akt and synaptophysin content and reduced ERK phosphorylation, and by the increase of active caspase-3 and p38 and Tau phosphorylation. Importantly, bezafibrate prevented MGA-elicited toxic effects towards mitochondrial function, redox homeostasis, and neural cell injury, implying that this compound may be potentially used as an adjunct therapy for MGTA and HMGA and other disorders with mitochondrial dysfunction.

Therapy of Canine Hyperlipidemia with Bezafibrate.

BACKGROUND: Bezafibrate (BZF) is effective in the treatment of hypertriglyceridemia in human patients, but there are no data on its use in dogs. OBJECTIVE: To assess the safety of BZF in hyperlipidemic dogs and its efficacy in decreasing serum triglyceride (TG) and cholesterol (CHO) concentrations. ANIMALS: Forty-six dogs, 26 females and 20 males, mean (±SD) age of 9 (±3) years, with TG ≥150 mg/dL (33 dogs also were hypercholesterolemic [>300 mg/dL]). METHODS: Prospective, uncontrolled clinical trial. Dogs were treated with bezafibrate once daily, using 200 mg tablets at a dosage of 4-10 mg/kg (depending on body weight). Serum TG and CHO concentrations and alanine aminotransferase (ALT) and creatine kinase (CK) activity before and after 30 days of treatment were compared. RESULTS: Sixteen dogs (34.8%) had primary hyperlipidemia, and 30 dogs (65.2%) had secondary hyperlipidemia (including spontaneous hyperadrenocorticism [41.3%, n = 19/46], chronic treatment with glucocorticoids [10.8%, n = 5/46], and hypothyroidism [15.2%, n = 7/46]). After 30 days, serum TG concentration normalized (<150 mg/dL) in 42 dogs (91.3%) and CHO concentration normalized (<270 mg/dL) in 22 of 33 dogs (66.7%). There was no difference in baseline TG concentration between the primary and secondary hyperlipidemia subgroups, but the decrease in TG concentration after treatment was greater in the primary hyperlipidemia subgroup. No adverse effects were observed, but ALT activity decreased significantly after 30 days of treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Over 30 days, BZF was safe and effective in treatment of primary and secondary hyperlipidemia in dogs.

Eficácia e tolerância do bezafibrato retard nas hiperlipidemias primárias / Efficacy and tolerance of bezafibrate retard in the primary hyperlipidemia

Em estudo aberto, näo comparativo, foram avaliados 25 pacientes portadores de hiperlipidemia primária. Deste total, 13 pacientes apresentavam hiperlipiproteinemia do tipo IIA de Fredrickson com níveis plasmáticos de colesterol acima de 220 mg/dl e 12 pacientes do tipo IIB com colesterol maior que 220 mg/dl e triglicérides acima de 250 mg/dl. Antes do início do tratamento o uso de medicamentos hipolipeniantes foi suspenso e os pacientes submetidos durante 60 dias à uma orientaçäo dietética. Durante os primeiros 30 dias os pacientes receberam placebo na posologia de um comprimido ao dia, seguido por um tratamento de 90 dias, durante o qual foi administrado um comprimido (400 mg) de bezafibrato retard ao dia. Ao término do tratamento houve uma reduçäo média da taxa de colesterol total (-17,1%), dos níveis de triglicérides (-38,6%) bem como um aumento de HDL-colesterol (+39,5%);-observou-se também uma queda de LDL-colesterol (-25,3%). Reaçöes colaterais ocorreram em nove casos sendo na maioria de intensidade leve, näo levando à suspensäo do tratamento

Tratamento de hipertensos essenciais, hipercolesterolêmicos com ou sem hipertrigliceridemia, com dose baixa de bezafibrato (200 mg/dia) / Treatment of essential hypertension, hypercholesterolemia with or without hypertriglyceridemia, with low dose of bezafibrate (200 mg/day)

Vinte hipertensos esenciais, cinco portadores de dislipidemia tipo IIa e 15, IIb, foram tratados com 200 mg/dia de bezafibrato. Um grupo semelhante, controle, näo medicado, näo apresentou diferenças significativas da lipidemia. Seis pacientes eram do sexo masculino (60 anos ñ 4) e 14 do feminino (57 anos ñ 2). A clesterolemia e a trigliceridemia foram valiadas antes do início da terapéutica (dia zero) e nos dias 28§ e 56§. A colesterolemia média inicial (n = 20) foi de 334 mg/dl ñ 10 E.P.§.), diminuindo significativamente para 274 ñ 7 e 279 ñ 11 (P < 0,01). A trigliceridemia média inicial (n = 15) foi de 544 mg/dl ñ 85, decrescendo significativamente (P < 0,01) para 234 ñ 36 e 245 ñ 36. A reduçäo porcentual média do colesterol foi de 16% ñ 4 e 14% ñ 5; a dos triglicérides, na dislipidemia IIb (n = 15), foi de 46% ñ 8, em ambos os dias 28§ e 56§. Näo foram constatados efeitos colaterais da droga. Concluíu-se que o bezafibrato (200 mg/dia) foi útil na melhora das dislipidemias de hipertensos essenciais, apesar dos pacientes näo terem modificado os hábitos alimentares e a atividade física, em curto prazo

[Treatment of essential hypertension and hypercholesterolemia with or without hypertriglyceridemia, with low dose of bezafibrate (200 mg/day)]. / Tratamento de hipertensos essenciais, hipercolesterolêmicos com ou sem hipertrigliceridemia, com dose baixa de bezafibrato (200 mg/dia).

Twenty patients with essential hypertension, 5 with dyslipidemia type IIa and 15 with that of type IIb, were treated with bezafibrate, 200 mg/day. As control group, 20 normo or dislipemic patients with essential hypertension receiving no hypolipidemic drugs, and chosen at random, showed no significant changes of the mean values of serum total cholesterol and triglycerides at three evaluations made in a period of about six months. Six patients were males (60 +/- 4 years) and 14 females (57 +/- 2 years). The levels of cholesterolemia and triglyceridemia were evaluated before the administration of the drug and on the 28th and 56th day of its use. The mean initial value of total cholesterol (n = 20) was 334 +/- 10 mg/dl, lowering significantly (P less than 0.01) to 274 +/- 7 mg/dl and 279 +/- 11 mg/dl. Initial triglyceridemia level (n = 15) was 544 +/- 85 mg/dl, decreasing significantly (P less than 0.01) to 234 +/- 36 and 245 +/- 36. Percentual mean decrease of cholesterolemia was respectively 16 +/- 4% and 14 +/- 5% and that of triglyceridemia was 46 +/- 8% for both evaluations. Side effects of the drug were not seen with the indicated dose. The therapy was useful to lower the dislipemic values of the essential hypertensive patients, in spite of no consistent changes in their diet and physical activity and of its use for a short period.

Comparaçäo dos efeitos hipolipemiantes da lovastatina e do bezafibrato em pacientes com hipercolesterolemia primária: estudo multicêntrico brasileiro / Comparison of lipid-lowering effects of lovastatin and bezafibrate in patients with primary hypercholesterolemia: the brazilian multicenter study

Cento e vinte e dois pacientes hipercolesterolêmicos foram acompanhados em estudo aleatório, duplo-cego por 22 semanas. Após 6 semanas de dieta hipolipemiante e quatro sob uso de placebo (período controle-PC), os pacientes foram alocados em dois extratos: El - 73 pacientes com colesterolemia total (CT) > ou = 250 mg e < 300 mg/dl e EII - 49 pacientes com CT > ou = 300 mg/dl. Os do EI foram tratados com Lovastatina (L) (Grupo L1) na dose de 20 mg/dia + placebo de bezafibrato (B) ou 600 mg de B + placebo de lobastatina (Grupo B1). Os do EII receberam L40 mg/dia + placebo B (Grupo L2) ou B 600 mg/dia + placebo L (Grupo B2). O período de tratamento ativo (PTA) durou 12 semanas, sendo determinados CT, TG, LDL-C, VLDL-C, HDL-c, CT/hdl-c (RI1) e LDL-c/HDL-c (RI2) no PC e ao final das 6ª e 1ª semanas do PTA. Controles clínicos, eletrocardiográficos, oftalmológicos e de outras variáveis laboratoriais foram realizados nas mesmas ocasiöes. Os dados foram submetidos à análise estatística, pela técnica multivariada de perfil de médias. O nível de significância estatística considerado foi p < 0.05. Os grupo L1, B1, L2 e B2 apresentaram respostas semelhantes em relaçäo a TG, HDL-C E VLDL-C. L1 e B1 sofreram reduçöes significativas de CT, LDL-C, IR1 e IR2 na sexta semana que se mantiveram até a décima segunda. L2 e B2 apresentaram para estes parâmetros reduçöes significativas na 6ª semana, que se intensificaram significativamente na 12ª semana apenas para L2. Foram os seguintes os decréscimos percentuais médios da 12ª semana em relaçäo ao PC