Abstract
Gamma amino butyric acid (GABA) has been reported to be renoprotective in various preclinical studies. Sodium valproate (SVP) is documented to protect against renal injury through its histone deacetylase-inhibiting activity. The present study investigated the involvement of GABAA receptors and the role of GABAergic activity of SVP against ischemia–reperfusion-induced acute kidney injury (AKI) in rats. The rats were subjected to bilateral renal ischemia for 40 min followed by reperfusion for 24 h to induce AKI. The creatinine clearance, serum urea, uric acid, lactate dehydrogenase, potassium, fractional excretion of sodium, and microproteinuria were measured to assess kidney injury. The thiobarbituric acid-reactive substances, reduced glutathione level, myeloperoxidase, and catalase activity were assayed to assess oxidative stress in renal tissues along with hematoxylin–eosin staining to observe histopathological changes. The ischemia–reperfusion-induced AKI witnessed an increase in serum parameters, microproteinuria, oxidative stress, and histopathological changes in renal tissues. Picrotoxin aggravated ischemia–reperfusion injury-induced AKI confirming the role of GABAA receptors in AKI. The SVP treatment afforded protection against AKI that was blocked by concurrent treatment with picrotoxin. Hence, it is concluded that regulation of GABAA receptors is important for management of AKI. Moreover, the GABAergic activity of SVP is important for its renoprotective effect.
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Brar, R., Singh, J.P., Kaur, T. et al. Role of GABAergic activity of sodium valproate against ischemia–reperfusion-induced acute kidney injury in rats. Naunyn-Schmiedeberg's Arch Pharmacol 387, 143–151 (2014). https://doi.org/10.1007/s00210-013-0928-2
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DOI: https://doi.org/10.1007/s00210-013-0928-2