Renoprotective effects of aliskiren on adenine-induced tubulointerstitial nephropathy: possible underlying mechanisms.
The present study investigated the possible renoprotective effect of direct renin inhibitor (aliskiren) on renal dysfunctions, as well as its underlying mechanisms in rat model of adenine-induced tubulointerstitial nephropathy. Forty male Sprague-Dawley rats were randomized into 4 groups; normal group, aliskiren group (normal rats received 10 mg/kg aliskiren), adenine group (animals received high-adenine diet for 4 weeks and saline for 12 weeks), and adenine + aliskiren group (animals received adenine for 4 weeks and aliskiren 10 mg/kg for 12 weeks). It was found that adenine caused significant decrease in body mass, Hb, HR, serum Ca(2+), eNOS and nrf2 expression, GSH, and catalase in kidney tissues with significant increase in arterial blood pressure (ABP), serum creatinine, BUN, plasma renin activity (PRA), K(+) and P, urinary albumin excretion (UAE), caspase-3, and MDA (lipid peroxidation marker) in kidney tissues compared to normal group (p < 0.05). Administration of aliskiren caused significant improvement in all studied parameters compared to adenine group (p < 0.05). We concluded that aliskiren has renoprotective effect against adenine-induced nephropathy. This might be due to inhibition of PRA, attenuation of oxidative stress, activation of Nrf2 and eNOS genes, and suppression of caspase-3.
a Medical Physiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Abdelaziz M
AM
Hussein
b Clinical Pharmacology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Hala Abdel
HA
Malek
b Clinical Pharmacology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Mohamed-Ahdy
MA
Saad
D000225:Adenine / Q000008:administration & dosage / Q000633:toxicity*; D000577:Amides / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D005650:Fumarates / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009395:Nephritis, Interstitial / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D020011:Protective Agents; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism; D000092502:Renin Inhibitors
D000225:Adenine; D000577:Amides; D005650:Fumarates; D020011:Protective Agents; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren
adenine; adénine; caspase-3; eNOS; nephropathy; nrf2; néphropathie; oxidative stress; stress oxidant