Oral Treatment with Angiotensin-(1-7) Attenuates the Kidney Injury Induced by Gentamicin in Wistar Rats

Abstract

Background: Acute Kidney Injury (AKI), a common disease of the urinary system, can be induced by high doses of gentamicin (GM). The Renin-Angiotensin System exerts a key role in the progression of the AKI since elevated intrarenal levels of Ang II, and ACE activity is found in this condition. However, it is unknown whether oral administration of Ang-(1-7), a heptapeptide that evokes opposite effects of Ang II, may attenuate the renal injuries induced by gentamicin. Objectives: To evaluate the effects of Ang (1-7) on GM-induced renal dysfunction in rats. Methods: AKI was induced by subcutaneous administration of GM (80 mg/Kg) for 5 days. Simultaneously, Ang-(1-7) included in hydroxypropyl β-cyclodextrin (HPβCD) was administered by gavage [46 μg/kg HPβCD + 30 μg/kg Ang- (1-7)]. At the end of the treatment period (sixth day), the rats were housed in metabolic cages for renal function evaluation. Thereafter, blood and kidney samples were collected. Results: The Ang-(1-7) attenuated the increase of the plasmatic creatinine and proteinuria caused by GM but did not change the glomerular filtration rate nor tubular necrosis. Ang-(1-7) attenuated the increased urinary flow and the fractional excretion of H2O and potassium observed in GM rats but intensified the elevated excretion of sodium in these animals. Morphological analysis showed that Ang-(1-7) also reduced the tubular vacuolization in kidneys from GM rats. Conclusion: Ang-(1-7) promotes selective beneficial effects in renal injuries induced by GM.

Mitigating Cardiotoxicity of Dendrimers: Angiotensin-(1-7) via Its Mas Receptor Ameliorates PAMAM-Induced Cardiac Dysfunction in the Isolated Mammalian Heart

“…The concept that Ang-(1-7) may serve as a novel therapeutic agent in mitigating cardiovascular toxicity of xenobiotics is further supported by the recent finding that Ang-(1-7) could reduce rat aortic arch dysfunction induced by the anti-cancer agent doxorubicin [65]. Additionally, Ang-(1-7) mitigated renal injury induced by gentamicin, an aminoglycoside antibiotic [66]. Thus, we propose that co-administration of Ang-(1-7) may represent a novel strategy to mitigate cardiotoxicity of nanoparticles in general as well as PAMAM dendrimers as described in our present study.…”

“…Thus, we propose that co-administration of Ang-(1-7) may represent a novel strategy to mitigate cardiotoxicity of nanoparticles in general as well as PAMAM dendrimers as described in our present study. As Ang-(1-7) is a peptide drug, to improve its biological stability and delivery in vivo, it can be formulated with cyclodextrins or even PAMAM delivery systems, which have been shown to be effective [66][67][68][69]. Furthermore, in clinical trials, Ang-(1-7) appears to be well tolerated and safe to use in humans [70,71].…”

Preconditioning by Moderate-Intensity Exercise Prevents Gentamicin-Induced Acute Kidney Injury

“…RAS and KKS components are involved in the development and progression of different forms of AKI [14][15][16][17]. Different works showed that blockade of the classical arm of RAS [18,19,70,71] or activation of the alternative arm of RAS [4,72] attenuates the gentamicin-induced AKI. Regarding KKS, Bledsoe et al [20] showed the activation of B 2 R ameliorated tubular injury induced by gentamicin.…”

“…Acute kidney injury (AKI) is a leading cause of morbidity and mortality worldwide [1,2]. AKI episodes are characterized by transient kidney dysfunction caused by different etiologies [3][4][5][6]. The use of aminoglycosides (AG), such as gentamicin, to treat life-threaten-ing infections is an important etiological factor of AKI [3,[7][8][9].…”

Reducing Oxygen Demand to Alleviate Acute Kidney Injury

“…Angiotensin 1-7 decreases oxygen consumption in the thick ascending limb of the loop of Henle and presumably in the proximal tubules as well [161]. Angiotensin 1-7 alleviates AKI in a variety of animal models [162][163][164][165]. However, whether it has a similar effect in humans remains unknown.…”