The protective effect of aminoguanidine on doxorubicin‐induced nephropathy in rats

Abstract

Reactive oxygen species and cytokines have been implicated in the nephrotoxicity induced by doxorubicin. The goal of the present study was to determine protective effect of aminoguanidine on doxorubicin-induced nephrotoxicity in rats. Different groups of male Wistar rats received doxorubicin (67.75 mg/kg/i.p./2 days), aminoguanidine alone and aminoguanidine (200 and 400 mg/kg/i.p./30 days) prior to doxorubicin, respectively. Doxorubicin significantly increased serum creatinine (505%), blood urea nitrogen (333%), nitric oxide (406%), and plasma tumor necrosis factor-alpha (706%) as well as urinary albumin (452%) and N-acetyl-β-D-glucosaminidase (415%) compared to control. Moreover, renal glutathione (334%), superoxide dismutase (283%), and catalase (513%) were significantly reduced accompanied with elevation in renal malondialdehyde compared to control. Pretreatment with aminoguanidine mitigated such changes in all mentioned parameters. Histopathological changes showed that doxorubicin-caused significant structural damages to kidneys that were reduced with aminoguanidine. Results indicate that reactive oxygen species and cytokines are involved in doxorubicin-induced nephrotoxicity, which can be reduced by aminoguanidine.

Aminoguanidine Protects Boar Spermatozoa against the Deleterious Effects of Oxidative Stress

“…In this sense, Balercia et al [43] found that asthenozospermic men show greater levels of NO • than normozoospermic men and that the concentration of this gasotransmitter were negatively correlated with the sperm motility. In this way, our findings indicate that aminoguanidine can be employed for protecting against the effects of oxidative stress in sperm cells, which is consistent with the findings in other cells and tissues (lung: [44]; bladder: [45]; kidney: [46]; testis: [29]). Similarly, Abbasi et al [30,31] and Alizadeh et al [32,33] found that the in vivo administration of aminoguanidine improves the sperm concentration, motility, viability, normal morphology, mitochondrial membrane potential, and DNA integrity in varicocelized rats where the upregulation of the iNOS isoform may lead to high levels of ROS in the semen.…”

Protective effects of molsidomine against doxorubicin-induced renal damage in rats

“…In the present study, DOX treatment caused a significant increase in TBARS levels and a significant decrease in GSH and CAT levels, when compared with the control group. These findings are in agreement with previous reports [25,29]. TBARS, a stable metabolite of the free radical mediated lipid peroxidation cascade, is widely used as a marker of oxidative stress and lipid layer destruction [30].…”

Curcumin ameliorates doxorubicin‐induced cardiotoxicity by abrogation of inflammation, apoptosis, oxidative DNA damage, and protein oxidation in rats

“…The most popular hypothesis is oxidative stress as a result of free radical production . The semiquinone form of DXR is a metabolite with a short life‐span and it starts a series of reactions that produce reactive oxygen species (ROS) after reacting with molecular oxygen . Moreover, it was reported that free radical production, mitochondrial dysfunction, calcium overload, and peroxynitrite also lead to DXR‐induced cardiotoxicity .…”

“…[2] The semiquinone form of DXR is a metabolite with a short life-span and it starts a series of reactions that produce reactive oxygen species (ROS) after reacting with molecular oxygen. [6,7] Moreover, it was reported that free radical production, mitochondrial dysfunction, calcium overload, and peroxynitrite also lead to DXR-induced cardiotoxicity. [8,9] It has been reported that DXR also increases inflammatory effects in the myocardium and the vasculature by increasing the expression of nuclear factor kappa-B (NF-B), a key regulator of genes that are involved in the inflammatory responses and immune responses.…”