Synergy of zinc oxide nanoparticles to losartan attenuates kidney injury induced by unilateral ureteral obstruction through modulation of the TNF-α/IL6 and BAX/BCL2 signaling pathways.

Abstract

Aim: Although the relief of ureteral obstruction seems to be a radical treatment for obstructive uropathy (OU), progressive kidney damage is the result because of the associated increased apoptosis and fibrosis. Therefore, it is urgent to find a complementary renoprotective therapy against partially obstructed uropathy cascades. Thus, this study investigated the renoprotective effects of both losartan (LOS) and zinc oxide nanoparticles (ZnONPs) in partial unilateral ureteral obstruction (PUUO).

Main methods: In controlled (n = 16) and shamed (n = 16) study, 64 healthy male Sprague-Dawley rats, both PUUO and right nephrectomy (RNX) were induced. The rats were equally allocated into four groups according to treatment protocol: (1) PUUO group (no treatment), (2) ZnONPs group, (3) LOS group and (4) ZnONPs/LOS group. Antioxidant status and gene expression were assessed in renal tissues. Moreover, histologic and immunohistochemical examinations were performed.

Key findings: LOS and ZnONPs significantly mitigated the PUUO-induced renal injury, by significant (P < 0.0001) suppressing of oxidative stress (MDA and TOS), upregulating of antioxidant gene (SOD) and antiapoptotic gene (BCL2), and downregulating the expression of inflammatory cytokines (TNF-α, and IL6), apoptotic gene (Bax) and fibrotic marker (β-Catenin). The combination of both agents offered a more powerful renoprotective effect with additional significant upregulation of the antioxidant marker (TAC, P < 0.0001).

Significance: Both losartan and ZnONPs and specially their combination have synergistic action in protecting the kidney against PUUO-induced chronic renal cascades through improvement the renal function tests, amelioration of oxidative stress, inhibition of induced apoptosis and fibrosis with marked renal regeneration which highlights the possible application of these drugs as a complementary therapies for different chronic renal degenerative diseases.