ACE2 activator diminazene aceturate exerts renoprotective effects in gentamicin-induced acute renal injury in rats

Abstract

Acute Kidney Injury (AKI) comprises a rapidly developed renal failure and is associated with high mortality rates. The Renin–Angiotensin System (RAS) plays a pivotal role in AKI, as the over-active RAS axis exerts major deleterious effects in disease progression. In this sense, the conversion of Angiotensin II (Ang II) into Angiotensin-(1-7) (Ang-(1-7)) by the Angiotensin-converting enzyme 2 (ACE2) is of utmost importance to prevent worse clinical outcomes. Previous studies reported the beneficial effects of oral diminazene aceturate (DIZE) administration, an ACE2 activator, in renal diseases models. In the present study, we aimed to evaluate the therapeutic effects of DIZE administration in experimental AKI induced by gentamicin (GM) in rats. Our findings showed that treatment with DIZE improved renal function and tissue damage by increasing Ang-(1-7) and ACE2 activity, and reducing TNF-α. These results corroborate with a raising potential of ACE2 activation as a strategy for treating AKI.

Activation of angiotensin-converting enzyme 2 ameliorates metabolic syndrome-induced renal damage in rats by renal TLR4 and nuclear transcription factor κB downregulation

“…Our results demonstrated that supplementation of MetS rats with DIZE significantly improved renal function parameters, and this finding is parallel to the renal histopathological results, which revealed that DIZE attenuated renal tubular and glomerular damage, suggesting that DIZE has a reno-protective effect against MetS-induced renal injury. This is consistent with the results of previous studies, which have demonstrated the reno-protective effects of DIZE in different rat models such as gentamicin-induced acute renal injury (45) and γirradiation induced renal damage (46). This ameliorative effect can be explained by the significant reduction in renal Ang II levels in MetS rats supplemented with DIZE, compared to MetS rats.…”

The effect of diminazene, an angiotensin‐converting enzyme 2 activator, on adenine‐induced chronic kidney disease in rats

“…It was shown that diminazene is also an ACE2 activator 7 . Diminazene was shown to have a renoprotective effect in different animal models 2,8–10 …”

Crocetin attenuating Urinary tract Infection and adherence of uropathogenic E. coli in NRK‐52E cells via an inflammatory pathway

“…Therefore, its indirect that gentamicin‐induced nephrotoxicity, especially to renal tubular epithelial cells, long treatment and use of large doses of antibiotics in the absence of xenobiotic metabolism (Kumar et al., 2013; McWilliam, 2015). Previously published research suggests that gentamicin‐induced apoptosis via the generation of reactive oxygen species (ROS) (De Almeida et al., 2020; Ma et al., 2018). During the gentamicin treatment, the host–pathogen interacts with the numerous immunogenic reactions to generate ROS, which further starts the inflammatory responses (Mestry et al., 2020).…”