I016: Losartan (L) enhances antioxidant defenses in renal tissue in normotensive hyperoxaluric rats (HoxR)

• Published in: American journal of hypertension 2000-04, Vol.13 (S2), p.180A-180A
• Main Authors: Toblli, J.E., de Cavanagh, E.M.V., Fraga, C.G., Ferder, L., Inserra, F.
• Format: Article
• Language: English
• Subjects: hyperoxaluria; Losartan; oxidative stress; renal tubulointerstitial lesions
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1016/S0895-7061(00)01163-8

Hyperoxaluria is a recognized cause of chronic tubulointerstitial lesions and this condition could contribute to develop arterial hypertension. Crystal deposition in the renal tubular cell produces injury due to free radicals overproduction. The aim of this study was to evaluate the effect of L on the oxidative stress (OxS) in a model of TI lesions (TIL) by hyperoxaluria by ethylene-glycol (ETG). Male Sprague-Dawley rats in 4 groups (G). G1) control, G2) ETG, G3) ETG + L, G4) L. G1 with regular tap water. ETG (1%) in drinking water “ad libitum” and L (40 mg/kg/day) by gavage were given for four weeks. On day 29 all the animals were sacrificed. Kidneys were processed by LM. TIL were graded by a semiquantitative score (0–4). Oxidative injury was evaluated by: 1) Total glutathione (TGSH) content, 2) Sufhydryles associated to proteins (−SH), 3) Se-glutathione peroxidase activity (Se-GPx) and 4) Lipid peroxidation (LP) as TBARS by fluorometry in kidney homogenates. (See Table) Mean ± sem On day 29 G1 (n = 6) Cont G2 (n = 6) ETG G3 (n = 6) ETG + L G4 (n = 6) L Urine Ox. (μg/bw/day) 1.3 ± 0.04 12.5 ± 0.62 11.9 ± 1.2 1.4 ± 0.08 TIL score 0.1 ± 0.1 1.6 ± 0.2 0.2 ± 0.1* 0.1 ± 0.1 −SH (nM/mg.Prot.) 82.8 ± 2.8 85.3 ± 10.3 117.3 ± 12.4* 151.8 ± 11.6 Se-GPx (mU/mg prot) 27.6 ± 2.1 40.6 ± 4 28 ± 3.3* 22.7 ± 2.3 TGSH (nM/ g ww) 263.4 ± 24.9 205.5 ± 28.9 360.3 ± 34.4* 297.8 ± 22.1 TBARS (nM MDA/ mg prot.) 0.70 ± 0.06 0.66 ± 0.09 0.35 ± 0.01* 0.35 ± 0.01 *p < 0.05 vs. G2. HoxR treated by L showed lower TIL score, lower TBARS and a higher level of antioxidant defenses. In conclusion: L seems to modify the OxS by ameliorate LP and protein peroxidation.