Improvement of Na+-K+ ATPase Activity and Gene Expression Associated with Glomerular Ultrastructural Protection in Diabetic Nephropathy by Acacia senegal: Role of Oxidative Stress Disturbances / Mejora de la actividad Na+-K+ ATPasa y la Expresión Génica Asociada con la Protección Ultraestructural Glomerular en la Nefropatía Diabética por Acacia senegal: Papel de las Alteraciones del Estrés Oxidativo

SUMMARY: This study assessed the effects of Acacia Senegal (AS) combined with insulin on Na+/K+-ATPase (NKA) activity and mRNA expression, serum glucose, renal function, and oxidative stress in a rat model of diabetic nephropathy (DN). Sixty rats were equally divided into six groups: normal control, normal+AS, diabetic (DM), DM+insulin, DM+AS, and DM+insulin+AS groups. Diabetes mellitus (type 1) was induced by a single injection of streptozotocin (65 mg/kg), and insulin and AS treatments were carried until rats were culled at the end of week 12. Serum glucose and creatinine levels, hemoglobin A1c (HbA1c) were measured. Renal homogenate levels of NKA activity and gene expression, malondialdehyde, superoxide dismutase (SOD), catalase and reduced glutathione (GSH) were evaluated as well as kidney tissue histology and ultrastructure. Diabetes caused glomerular damage and modulation of blood and tissue levels of creatinine, glucose, HbA1c, malondialdehyde, NKA activity and gene expression, SOD, catalase and GSH, which were significantly (p<0.05) treated with AS, insulin, and insulin plus AS. However, AS+insulin treatments were more effective. In conclusion, combined administration of AS with insulin to rats with DN decreased NKA activity and gene expression as well as oxidative stress, and improved glycemic state and renal structure and function.

Este estudio evaluó los efectos de Acacia senegal (AS) combinada con insulina sobre la actividad Na+/K+- ATPasa (NKA) y la expresión de ARNm, la glucosa sérica, la función renal y el estrés oxidativo en un modelo de nefropatía diabética (ND) en ratas. Sesenta ratas se dividieron equitativamente en seis grupos: control normal, normal+AS, diabética (DM), DM+insulina, DM+AS y DM+insulina+AS. La diabetes mellitus (tipo 1) se indujo mediante una única inyección de estreptozotocina (65 mg/kg), y los tratamientos con insulina y AS se llevaron a cabo hasta que las ratas fueron sacrificadas al final de la semana 12. Se midieron niveles séricos de glucosa y creatinina, hemoglobina A1c (HbA1c). Se evaluaron los niveles de homogeneizado renal de actividad NKA y expresión génica, malondialdehído, superóxido dismutasa (SOD), catalasa y glutatión reducido (GSH), así como la histología y ultraestructura del tejido renal. La diabetes causó daño glomerular y modulación de los niveles sanguíneos y tisulares de creatinina, glucosa, HbA1c, malondialdehído, actividad y expresión génica de NKA, SOD, catalasa y GSH, los cuales fueron tratados significativamente (p<0,05) con AS, insulina e insulina más AS. Sin embargo, los tratamientos con AS+insulina fueron más efectivos. En conclusión, la administración combinada de AS con insulina a ratas con DN disminuyó la actividad de NKA y la expresión genética, así como el estrés oxidativo, y mejoró el estado glucémico y la estructura y función renal.

A high-fat diet rich in corn oil exaggerates the infarct size and memory impairment in rats with cerebral ischemia and is associated with suppressing osteopontin and Akt, and activating GS3Kß, iNOS, and NF-κB.

The increase in osteopontin (OPN) levels after stroke induces neural protection by activating Akt signaling and inhibiting GS3Kß, iNOS, and NF-κB. This study investigated the effect of a high-fat diet rich in corn oil (CO-HFD) on infarct size and memory function in rats after induction of cerebral ischemia in rats and investigated its effect on the expression of OPN/Akt/iNOS/NF-κB signaling pathways. Rats were initially fed a standard diet (STD, 3.82 kcal/g; 9.4%, from fat) or a CO-HFD (5.4 kcal/g, 40% from fat) for 12 weeks. Then, both groups were further subdivided into either sham group or group exposed to cerebral ischemia by the middle cerebral artery occlusion (MCAO) protocol. Compared with sham-operated rats fed STD diet, neurological scores and both short- and long-term memory functions were significantly impaired in sham-operated CO-HFD-fed rats. In addition, brains collected from CO-HFD-fed rats showed lower protein levels of OPN, p-Akt (Thr308), p-GS3Kß (Ser9), and Bcl-2 and had higher protein levels of iNOS, cleaved caspase-3, nuclear NF-κB p65, and cytoplasmic cytochrome C. However, once exposed to MCAO surgery, similar but more profound alterations of all these biochemical parameters with more severe impairment in short- and long-term memory functions and larger infarct size were noticed in the brains of CO-HFD-fed rats as compared with STD-fed rats exposed to MCAO. In conclusion, chronic consumption of CO-HFD induces memory impairments and worsens memory function recovery and infarct size after cerebral ischemia in rats by reducing levels of OPN, inhibiting the activation of Akt and activating iNOS and NF-κB.