Efecto de trimetazidina en la nefrotoxicidad por gentamicina / Trimetazidine effect on nephrotoxicity by gentamicyn

La Trimetazidina (TMZ) es una droga utilizada como cardioprotector, ya que previene la muerte celular secundaria a la isquemia miocárdica. Algunos investigadores le atribuyeron efecto reno-protector, actividad antioxidante y scavenger de radicales libres del oxígeno. El objetivo del presente trabajo es mostrar el efecto citoprotector de TMZ en las alteraciones inducidas por Gentamicina (G) a nivel de la célula del túbulo renal. Se diseñaron esquemas en animales de experimentación tratados con ambas drogas. Ratas macho Wistar de 180 a 200 g de peso fueron distribuidas en 5 grupos (n=8) y tratadas con: dieta estándar (A); suplementada con 20 mg/Kg/día de TMZ durante 27 días (B); suplementada con 50 mg/Kg/día de G durante 7 días(C); pretratadas 20 días con 20 mg/Kg/día de TMZ y los últimos 7 días con G (D) y tratadas simultáneamente durante 7 días con 20 mg/Kg/día de TMZ y 50 mg/Kg/día de G(E). Se midieron los compuestos nitrogenados urea y creatinina, la excreción de gamma glutamiltranspeptidasa urinaria y se efectuaron estudios estructurales con tinción de hematoxilina-eosina y ultraestructurales. Se utilizó el grupo C como testigo de nefrotoxicidad inducida por G. El pretratamiento durante 20 días con TMZ demostró el efecto protector para la nefrotoxicidad inducida, sin cambios bioquímicos-funcionales, ni alteración de la histoarquitectura, ni de la ultraestructura. El tratamiento simultáneo con TMZ y G no mostró efecto protector. Se concluye que en el modelo de ratas macho Wistar se demuestra el efecto citoprotector de TMZ en tratamiento previo por 21 días. El estudio histológico del tejido renal, bajo estas condiciones, presenta histoarquitectura conservada y función renal normal. Se infiere que el efecto citoprotector de TMZ que impide la nefrotoxicidad inducida por G se debe a la inhibición de la reabsorción y acumulación de Gentamicina en la célula del túbulo proximal del nefrón.

Trimetazidine (TMZ) is a drug used as a cardioprotector since it prevents cell death secondary to myocardial ischemia. Some investigators have attributed protective effect, antioxidant activity and oxygen free radical scavenging abilityt to TMZ. The aim of the present work is to show the cytoprotective effect of TMZ on Gentamicin (G)-induced alterations at the level of the renal tubular cell. Schemes were designed in experimental animals treated with both drugs. Male Wistar rats weighing 200 to 260 g were divided into 5 groups (n=8) and treated with: standard diet (A); standard diet supplemented with 20 mg/Kg/day of TMZ for 27 days (B); standard diet supplemented with 50 mg/Kg/day of G for 7 days (C), pretreated for 20 days with 20 mg/Kg/day of TMZ and for the last 7 days with G (D), and treated simultaneously for 7 days with 20 mg/Kg/day of TMZ and 50 mg/Kg/day of G (E). The nitrogen compounds urea and creatinine were measured and so was the excretion of urinary gamma-glutamyl transpeptidase. Structural studies with hematoxilin and eosin staining and ultrastructural studies were also performed. Gentamicin was used as a control for nephrotoxicity (group C). Pretreatment with TMZ showed a protective effect against induced nephrotoxicity, with no biochemical changes or alterations in the histoarchitecture. Simultaneous treatment with TMZ and G (group E) showed no protective effect. Conclusions: the cytoprotective effect of TMZ on G-induced nephrotoxicity would take place at the level of the proximal tubular cell of the brush border by inhibiting G reabsorption and accumulation.

Angina pectoris; role of trimetazidine

To assess the clinical efficacy, cost effectiveness and side effect profile of trimetazidine in the management of stable angina pectoris. An open label, uncontrolled study was conducted in 200 patients with stable angina in armed forces institute of cardiology, Rawalpindi Pakistan. Patients were treated for 4 weeks with modified release trimetazidine tablet [35 mg] twice daily in addition to their conventional therapy. As compared to base line trimetazidine significantly reduced the number of angina episodes per week from 10 to 3 [p<0.005], improved exercise duration time on standard exercise tolerance test [ETT] [410 vs. 370 sec; p<0.01], time to onset of typical angina [380 vs. 290 sec; p<0.05], time to 1mm or more ST segment depression [340 vs. 290 sec; p<0.01]. There was no drop out of patients due to side effects or non compliance. These results indicate that trimetazidine is effective and well tolerated when used in combination with existing antianginal therapy in patients with angina pectoris