British journal of clinical pharmacology · 2026
Possible therapeutic repositioning of valproic acid: From epileptic seizures to acute kidney injury.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Alves-Bezerra Danilo, Negreiros Luiza B, Pereira-Acácio Amaury, Almeida Isadora G, Veloso-Santos João P M, Lopes Jarlene A, Costa-Sarmento Glória, Muzi-Filho Humberto, Vieyra Adalberto
Аннотация
AIMS: Valproic acid is an inhibitor of histone deacetylases (HDACs) and is used for the treatment of epileptic seizures. The drug (sodium valproate) has antihypertensive effects, and HDACs modulate renal Na+-transporting ATPases. The aim was to investigate whether valproate could be repositioned as an adjunctive drug for the prevention of acute kidney injury (AKI).
METHODS: AKI due to ischemia followed by reperfusion (I/R) was induced by clamping of the renal arteries in rats that had received valproate or a vehicle for 20 days. Plasma creatinine and urea concentrations, and glomerular filtration rate (colorimetrically); plasma and urinary Na+ and K+ concentrations, and urinary excretion of Na+ and K+ (spectrophotometrically); proximal tubules (Na++K+)ATPase activity (release of Pi from ATP); and blood pressure (pletismography) were measured 48 h later.
RESULTS: AKI increases plasma creatinine and returns to baseline values observed in non-operated animals when I/R rats are pretreated with valproate. Its decrease in urine is significantly prevented by valproate administration. The elevated plasma urea concentration is significantly reduced. Urinary excretion of Na+ and K+ decreases in I/R, but while the former is recovered by valproate, this does not occur with K+. The plasma levels of both ions remain ~10% below those of Sham controls. The decrease in (Na++K+)ATPase activity in I/R rats is totally prevented by valproate. The AKI-provoked hypertension is prevented by valproate.
CONCLUSIONS: Valproate has pharmacological properties that point to its potential repositioning as an adjuvant in improving several outcomes in AKI and potentially avoiding progression to chronic kidney disease.
METHODS: AKI due to ischemia followed by reperfusion (I/R) was induced by clamping of the renal arteries in rats that had received valproate or a vehicle for 20 days. Plasma creatinine and urea concentrations, and glomerular filtration rate (colorimetrically); plasma and urinary Na+ and K+ concentrations, and urinary excretion of Na+ and K+ (spectrophotometrically); proximal tubules (Na++K+)ATPase activity (release of Pi from ATP); and blood pressure (pletismography) were measured 48 h later.
RESULTS: AKI increases plasma creatinine and returns to baseline values observed in non-operated animals when I/R rats are pretreated with valproate. Its decrease in urine is significantly prevented by valproate administration. The elevated plasma urea concentration is significantly reduced. Urinary excretion of Na+ and K+ decreases in I/R, but while the former is recovered by valproate, this does not occur with K+. The plasma levels of both ions remain ~10% below those of Sham controls. The decrease in (Na++K+)ATPase activity in I/R rats is totally prevented by valproate. The AKI-provoked hypertension is prevented by valproate.
CONCLUSIONS: Valproate has pharmacological properties that point to its potential repositioning as an adjuvant in improving several outcomes in AKI and potentially avoiding progression to chronic kidney disease.