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.(AU)

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.(AU)

Response surface methodology for optimization of production of lovastatin by solid state fermentation

Lovastatin, an inhibitor of HMG-CoA reductase, was produced by solid state fermentation (SSF) using a strain of Aspergillus terreus UV 1718. Different solid substrates and various combinations thereof were evaluated for lovastatin production. Wheat bran supported the maximum production (1458 ± 46 µg g-1 DFM) of lovastatin. Response surface methodology (RSM) was applied to optimize the medium constituents. A 2(4) full-factorial central composite design (CCD) was chosen to explain the combined effects of the four medium constituents, viz. moisture content, particle size of the substrate, di-potassium hydrogen phosphate and trace ion solution concentration. Maximum lovastatin production of 2969 µg g-1 DFM was predicted by the quadratic model which was verified experimentally to be 3004 ± 25 µg g-1 DFM. Further RSM optimized medium supplemented with mycological, peptone supported highest yield of 3723.4±49 µg g-1 DFM. Yield of lovastatin increased 2.6 fold as with compared to un-optimized media.

Production of angkak through co-culture of Monascus purpureus and Monascus ruber

Angkak (red mold rice, red yeast rice, Chinese red rice) is a traditional Chinese medicine produced by solid-state fermentation of cooked non-glutinous rice with Monascus species. The secondary metabolite of Monascus species, monacolin K /lovastatin, has been proven to lower blood lipid levels. In this study, a co-culture of Monascus purpureus MTCC 369 and Monascus ruber MTCC 1880 was used for angkak production. Four medium parameters screened by Plackett-Burman design were optimized by response surface methodology for highest lovastatin production in angkak during solid-state fermentation by the co-culture. Maximum lovastatin production of 2.84 mg g-1 was predicted in solid medium containing 20 g rice and 40 ml liquid nutrients medium (malt extract 9.68 g l-1, dextrose 38.90 g l-1, MnSO4.H2O 1.96 g l-1, and MgSO4.7H2O 0.730 g l-1) by point prediction tool of Design Expert 7.1 software (Statease Inc. USA).

Production of angkak through co-culture of Monascus purpureus and Monascus ruber

Angkak (red mold rice, red yeast rice, Chinese red rice) is a traditional Chinese medicine produced by solid-state fermentation of cooked non-glutinous rice with Monascus species. The secondary metabolite of Monascus species, monacolin K /lovastatin, has been proven to lower blood lipid levels. In this study, a co-culture of Monascus purpureus MTCC 369 and Monascus ruber MTCC 1880 was used for angkak production. Four medium parameters screened by Plackett-Burman design were optimized by response surface methodology for highest lovastatin production in angkak during solid-state fermentation by the co-culture. Maximum lovastatin production of 2.84 mg g-1 was predicted in solid medium containing 20 g rice and 40 ml liquid nutrients medium (malt extract 9.68 g l-1, dextrose 38.90 g l-1, MnSO4.H2O 1.96 g l-1, and MgSO4.7H2O 0.730 g l-1) by point prediction tool of Design Expert 7.1 software (Statease Inc. USA).

Proteção funcional do rim com lovastatina após isquemia e reperfusão renal

Acute kidney ischemia is a frequent clinical problem in vascular and urologic surgery, as in cadaver donor transplantation. In the search for an improvement in renal function, in this study we assessed the effect of lovastatin on kidney ischemia-reperfusion. Adult Wistar rats were submitted to 60 minutes of unilateral kidney ischemia followed by contralateral nephrectomy, with 7 days of follow-up. The experimental group (n=14) received 15 mg/Kg/day of lovastatin and the control group (n=17) had no protection against kidney ischemia. Serum urea and cretinine, death rate and mitochondrial function were analysed into each group. Death rate was 29.4% in group A and 0.7% in group B. Serum levels of urea and creatinine raised in both group, but in group B these values were statistically lower. In 83.4% of the group A animals mitochondrial function showed no ATP production, and in group B this condition was seen in only 38.4%. These results suggest that lovastatin has a protective effect on renal function when administered before kidney ischemia. However, at this moment it is impossible to confirm that this action is due to a protective effect on mitochondrial function.

Introdução - a isquemia renal é causa de graves lesões nesse órgão, estando presente em diferentes situações como em cirurgias renais, vasculares e no transplante renal. Assim, a procura de substâncias protetoras da função renal tem amplo interesse clínico. Neste estudo o objetivo foi o de analisar o efeito da lovastatina na isquemia renal normotérmica seguida da reperfusão.

PROTEÇÃO FUNCIONAL DO RIM COM LOVASTATINA APÓS ISQUEMIA E REPERFUSÃO RENAL

Acute kidney ischemia is a frequent clinical problem in vascular and urologic surgery, as in cadaver donor transplantation. In the search for an improvement in renal function, in this study we assessed the effect of lovastatin on kidney ischemia-reperfusion. Adult Wistar rats were submitted to 60 minutes of unilateral kidney ischemia followed by contralateral nephrectomy, with 7 days of follow-up. The experimental group (n=14) received 15 mg/Kg/day of lovastatin and the control group (n=17) had no protection against kidney ischemia. Serum urea and cretinine, death rate and mitochondrial function were analysed into each group. Death rate was 29.4% in group A and 0.7% in group B. Serum levels of urea and creatinine raised in both group, but in group B these values were statistically lower. In 83.4% of the group A animals mitochondrial function showed no ATP production, and in group B this condition was seen in only 38.4%. These results suggest that lovastatin has a protective effect on renal function when administered before kidney ischemia. However, at this moment it is impossible to confirm that this action is due to a protective effect on mitochondrial function.

Introdução - a isquemia renal é causa de graves lesões nesse órgão, estando presente em diferentes situações como em cirurgias renais, vasculares e no transplante renal. Assim, a procura de substâncias protetoras da função renal tem amplo interesse clínico. Neste estudo o objetivo foi o de analisar o efeito da lovastatina na isquemia renal normotérmica seguida da reperfusão.

Effects of cholestyramine and lovastatin upon plasma lipids and egg yolk cholesterol levels of laying hens / Efeitos da colestiramina e da lovastatina sobre os lípides plasmáticos e teores de colesterol da gema do ovo de galinhas poedeiras

The purpose of this study was to evaluate the effect of cholestyramine and lovastatin, lipid-lowering agents, upon egg quality, reproductive performance, plasma lipids and egg yolk cholesterol levels of Shaver laying hens. Twenty-six-weeks-old hens were fed basal diet without animal products containing 0.2% cholestyramine (COL1), 0.3% cholestyramine (COL2) or 0.005% lovastatin (LOV) for 6 weeks. It was observed that the supplementation of the drugs did not impair albumen and shell quality. Hen performance was not adversely affected, with the exception of the significant reduction (p 0.05) in egg weights. No significant changes were observed on plasma lipids, and egg yolk cholesterol remained unchanged with the addition of the drugs.

O presente trabalho teve por objetivo avaliar os efeitos da colestiramina e da lovastatina, drogas hipolipemizantes, sobre a qualidade do ovo, desempenho das aves, teores de lípides plasmáticos e de colesterol na gema do ovo de galinhas poedeiras Shaver. Aves com 26 semanas de idade receberam como alimentação dieta formulada sem ingredientes de origem animal (COM) acrescida de colestiramina a 0,2% (COL1) e 0,3% (COL2) e lovastatina a 0,005% (LOV) durante 6 semanas. A adição das drogas não prejudicou a qualidade da casca e do albúmen dos ovos. De um modo geral, o desempenho produtivo das aves não foi afetado, com exceção da redução observada no peso médio dos ovos. Não foram observadas mudanças nos teores de lípides plasmáticos das aves e a concentração de colesterol na gema permaneceu inalterada mediante a adição das drogas.