Effects of Losartan, Tempol, and Their Combination On Renal Nitric Oxide Synthases in the Animal Model of Chronic Kidney Disease

Abstract

Down-regulation of nitric oxide synthase (NOS) and NO defi ciency in the kidneys have been implicated in the pathogenesis of chronic kidney disease (CKD). In this study we examined the effects of losartan, tempol, and combined treatment on three NOS isoforms expressions, kidney NO content and NOS correlation with renal function and structure in the early stage of adriamycin (ADR)-induced CKD in spontaneously hypertensive rats (SHR). Rats were divided into control group, and four other groups which were treated with ADR and received vehicle, losartan (L, angiotensin II type 1 receptor blocker), tempol (T, redox-cycling nitroxide) or T+L treatment (by gavage) in a six-week study. Reduction of all NOS isoforms expressions were signifi cantly improved by losartan or tempol, and correlated with proteinuria amelioration. Combined treatment induced down-regulation of constitutive NOS isoforms, whilst inducible NOS was up-regulated and followed by increased nitrite content and a signifi cant decline in the glomerular fi ltration rate. Losartan or tempol prevented ADR-induced neoexpression of vimentin in the glomeruli and tubulointerstital areas, whereas de novo vimentin expression was still observed in the atrophic tubules and in the interstitial fi broblasts and myofi broblasts in combined treatment. It can be concluded that single treatments, contrary to combined, were effective in improving NO bioavailability and slowing down the progression of CKD.

Olive leaf extract attenuates adriamycin‐induced focal segmental glomerulosclerosis in spontaneously hypertensive rats via suppression of oxidative stress, hyperlipidemia, and fibrosis

“…The development of ADR-induced nephropathy in SHR resembling to the early stage of FSGS is well documented in our earlier studies (Karanovic et al, 2016(Karanovic et al, , 2017Mihailovic-Stanojevic et al, 2009). In SHR injected with ADR, along with hypoalbuminemia and albuminuria, we detected glomerulosclerosis, tubular injury, interstitial inflammatory cells infiltration, and fibrosis that were accompanied with increased collagen deposition, fibronectin overexpression, and HO deficiency in the kidney.…”

“…Kidney tissue samples (six rats per group) were homogenized in lysis buffer (Karanovic et al, 2017), and with an equal amount of protein were separated by SDS‐PAGE and electrotransferred to nitrocellulose membrane. The membranes were incubated with the primary antibodies: SOD1 (1:2000, ab16831), CAT (1:2000, ab16731), GPx (1:1000, ab59546), HO‐1 (1:250, ab13248), HO‐2 (1:1000, ab90515), BVR (1:1000, ab19260), NF‐kB p65 subunit (1:500, MAB3026), TNF‐α (1:1000, ab6671), TGF‐β (1:1000, ab66043), fibronectin (1:1000, ab2413), and actin (1:500, A5060).…”

“…Kidney tissue samples (six rats per group) were homogenized in lysis buffer (Karanovic et al, 2017), and with an equal amount of protein were separated by SDS-PAGE and electrotransferred to nitrocellulose membrane. The membranes were incubated with the primary antibodies: SOD1 (1:2000, ab16831), CAT (1:2000, ab16731), GPx…”

Hyperbaric Oxygen Reduces Oxidative Stress Impairment and DNA Damage and Simultaneously Increases HIF-1α in Ischemia–Reperfusion Acute Kidney Injury

“…Kidney tissue samples were taken from six rats per group and homogenized in lysis buffer [92], and with an equal amount of protein, they were separated by 10% SDS-PAGE and transferred to nitrocellulose membrane. The membranes were incubated with the primary antibodies: HIF-1 alpha (1:1000, H6536 Sigma-Aldrich) and actin (1:500, A5060 Sigma-Aldrich).…”