Protective effect of aminoguanidine against oxidative stress and bladder injury in cyclophosphamide‐induced hemorrhagic cystitis in rat

Abstract

Cyclophosphamide (CP) is an antineoplastic agent that is used for the treatment of many neoplastic diseases. Hemorrhagic cystitis (HC) is a major dose limiting side effect of CP. Recent studies show that aminogaunidine, an inhibitor of inducible nitric oxide synthase is a potent antioxidant and prevents changes caused by oxidative stress such as depletion of antioxidant activity and tissue injury. The purpose of the study is to investigate the effect of aminoguanidine on parameters of oxidative stress, antioxidant enzymes and bladder injury caused by CP. Adult male rats were randomly divided into four groups. Control rats were administered saline; the AG control group received 200 mg/kg body wt of aminoguanidine; The CP group received a single injection of CP at the dose of 150 mg/kg body wt intraperitoneally. The CP þAG group received aminoguanidine (200 mg/kg body wt) intraperitoneally 1 h before the administration of CP. The rats were sacrificed 16 h after CP/saline administration. The bladder was used for light microscopic studies and biochemical studies. The markers of oxidative damage including protein carbonyl content, protein thiol, malondialdehyde and conjugated dienes were assayed in the homogenates along with the activities of the antioxidant enzymes, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase and glutathione S transferase. In the bladders of CP treated rats edema of lamina propria with epithelial and sub-epithelial hemorrhage was seen. All the parameters of oxidative stress that were studied were significantly elevated in the bladders of CP treated rats. The activities of the antioxidant enzymes were significantly lowered in the bladders of CP treated rats. Aminoguanidine pretreatment prevented CP-induced oxidative stress, decrease in the activities of anti-oxidant enzymes and reduced bladder damage. The results of the present study suggest the antioxidant role for aminoguanidine in CP-induced bladder damage.

Oral Glutamine Attenuates Cyclophosphamide-Induced Oxidative Stress in the Bladder but Does Not Prevent Hemorrhagic Cystitis in Rats

“…These include α-tocopherol, β-carotene, taurine, and melatonin [4][5][6]. In a recent study, we have shown that aminoguanidine pretreatment attenuates CP-induced oxidative stress, decrease in the activities of antioxidant enzymes, and reduced bladder damage [25].…”

Urothelial Signaling

“…Excess NO levels have been linked to changes in epithelial barrier function in a number of pathologies including BPS/IC (175,231). Studies have shown that both aminoguanidine and TGF-␤1 inhibit expression of iNOS and have been shown to prevent changes in urinary bladder following cyclophosphamide treatment in rats (1,162).…”

Effects of fructosamine-3-kinase deficiency on function and survival of mouse pancreatic islets after prolonged culture in high glucose or ribose concentrations

“…However, the correlation between changes in protein glycation and ␤-cell glucotoxic alterations was rather poor in these studies, thereby raising questions about the causal link between both events (24,39). It is indeed possible that the beneficial effects of aminoguanidine on ␤-cell glucotoxicity may be unrelated to the reduction in protein glycation but rather depend, like those of NAC, on the reduction of oxidative stress (1,17). Despite the lack of effect of FN3K deficiency on ␤-cell function after culture in G10 and G30, our study does not formally exclude the possibility that protein glycation plays a role in ␤-cell glucotoxicity.…”