Эффекты ниацин-оксиэтилидендифософнат германата и альфа-липоевой кислоты на диабет-индуцированный оксидантный стресс в ткани сетчатки

Odessa National Medical University, Odessa, Ukraine, Conferinţa știinţifică cu participare internaţională ”Actualităţi în farmacologie și în farmacologia clinică” întru comemorarea celor 100 de ani de la nașterea ilustrului savant, profesor universitar, laureat al Premiului de Stat al Republicii Moldova Efim Muhin 29 noiembrie – 1 decembrie 2018 Chișinău, Republica MoldovaEffects of two weeks treatment with niacin-oxyethylidendiphosphonatogermanate (MIGU-4, 2,5; 25,0 mg/kg, i.p.) and alpha-lipoic acid (LA, 5,0 and 50,0 mg/kg, i.p.) as well as their combined usage (MIGU-4 – 2,5, and LA – 5,0 mg/kg) upon antioxidative enzymes and level of malon dialdehyde (MDA) in retina tissue of rats with streptozotocin (STZ)induced diabetes was determined. It was established that in six weeks after STZ administration superoxiddismutase (SOD) activity decreased by 33,4% (P<0,05), catalase (CAT) – by 28,2% (P<0,05), glutathione peroxidase (GPx) – by 39,8%, glutathione reductase (GR) – by 48,3%, and MDA level raised by 2,65 times when compared with intact rats (P<0,05). MIGU-4 treatment (25,0 mg/kg, i.p.) increased SOD activity by 38,1% (P<0,05), GPx and GR – by 62,9% (P<0,05) and by 35,2% (P<0,05), when compared with diabetes rats. MDA level was reduced by 30,2% (P<0,05) correspondently. The SOD activity under condition of combined MIGU-4 (2,5 mg/ kg) and LA (5,0 mg/kg) administration exceeded its level in rats with diabetes by 41,3% (P<0,05), while activity of GPx and GR also was higher by 52,4% and by 47,8% (P<0,05) correspondently. MDA level reduction was higher than in groups which were given MIGU-4 or LA alone (P<0,05). Thus, niacin-oxyethylidendiphosphonato-germanate caused prevention on diabetes-induced deterioration of antioxidant enzymes activity and level of MDA in retina tissue. Combined usage of MIGU-4 and LA was resulted in heightened preventive effects upon manifestations of oxidative stress.Au fost investigate efectele administrării de două săptămani a hidroxietilidendifosfonat germanatului (MIGU-4, 2,5; 25,0 mg/kg, i.p.) şi a acidului alfa-lipoic (LC, 5,0 şi 50,0 mg/kg, i.p.) şi efectul utilizării lor combinate (MIGU-4 – 2,5 şi LC – 5,0 mg/kg) asupra activităţii enzimelor antioxidante şi nivelului de malondialdehidă (MDA) in ţesutul retinei şobolanilor cu diabet indus de streptozotocină (STZ). S-a constatat că după 6 săptămani de la momentul aplicării STZ, activitatea superoxid dismutazei (SOD) a scăzut cu 33,4% (P <0,05), a catalazei (CAT) – cu 28,2% (P <0,05), a glutationperoxidazei – cu 39,8%, a glutationreductazei (GR) – cu 48,3%, cu o creştere a conţinutului de MDA de 2,65 ori, comparativ cu şobolanii intacţi (P <0,05). Odată cu introducerea MIGU-4 (25,0 mg/kg, i.p.), activitatea SOD a fost mai mare cu 38,1% (P <0,05), a HP şi GR – cu 62,9% (P <0,05 ) şi, respectiv, 35,2% (P <0,05), in comparaţie cu animalele cu diabet zaharat. Nivelul MDA a scăzut cu 30,2% (P <0,05). Eficacitatea MIGU-4 (25,0 mg/ kg) a fost comparabilă cu cea a LK utilizată in doză de 50,0 mg/kg. In cazul folosirii combinate a MIGU-4 (2,5 mg/kg) şi a LC (5,0 mg/kg), activitatea SOD a depăşit-o pe cea a şobolanilor cu diabet zaharat cu 41,3% (P <0,05), GP şi GR fiind mai mari cu 52,4% şi, respectiv, cu 47,8% (P <0,05). Scăderea nivelului MDA a fost mai mare decat in cazul grupurilor care utilizează MIGU-4 sau LC (P <0,05). Astfel, administrarea hidroxietildidenfosfonat germanatului previne dereglările activităţii enzimelor antioxidante şi nivelului MDA induse de diabet in ţesutul retinian. Administrarea asociată a MIGU-4 şi a LC este insoţită de o acţiune preventivă sporită impotriva manifestărilor stresului oxidativ.Исследовали влияние двухнедельного введения ниациноксиэтилидендифосфонат германата (МИГУ-4, 2,5; 25,0 мг/кг, в/бр) и альфа-липоевой кислоты (ЛК, 5,0 и 50,0 мг/кг, в/бр), а также влияние их совместного применения (МИГУ-4 – 2,5, и ЛК – 5,0 мг/кг) на активность антиоксидантних ферментов и уровень малонового диальдегида (МДА) в ткани сетчатки крыс со стрептозотоцин (СТЗ)-индуцированным диабетом. Установлено, что через 6 недель с момента применения СТЗ активность супероксидисмутазы (СОД) уменьшилась на 33,4% (P<0,05), каталазы (КАТ) – на 28,2% (P<0,05), глутатионпероксидазы (ГП) – на 39,8%, глутатионредуктазы (ГР) – на 48,3% при увеличении содержания МДА в 2,65 раза в сравнении с интактными крысами (P<0,05). На фоне введения МИГУ-4 (25,0 мг/кг, в/бр) активность СОД была выше на 38,1% (P<0,05), ГП и ГР – на 62,9% (P<0,05) и соответственно 35,2% (P<0,05) при сравнении с животными с диабетом. При этом уровень МДА уменьшался на 30,2% (P<0,05). При комбинированном применении МИГУ-4 (2,5 мг/кг) и ЛК (5,0 мг/кг) активность СОД превышала таковую у крыс с диабетом на 41,3% (P<0,05), в то время как активность ГП и ГР была выше на 52,4% и соответственно 47,8% (P<0,05) соответственно. Величина снижения уровня МДА была выше, чем в группах с применением одного МИГУ-4 или ЛК (P<0,05). Таким образом, применение ниацин-оксиэтилидендифосфонат германата предотвращает диабет-вызванные нарушения активности антиоксидантных ферментов и уровня МДА в ткани сетчатки. Совместное введение МИГУ-4 и ЛК сопровождается потенцированным превентивным действием в отношении проявлений оксидативного стресса

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