Contribution of γ glutamyl transpeptidase to oxidative damage of ischemic rat kidney

Cutrìn, Juan Carlos; Zingaro, Barbara; Camandola, Simonetta; Boveris, Alberto; Pompella, Alfonso; Poli, Giuseppe

doi:10.1046/j.1523-1755.2000.00871.x

Cited by 33 publications

(20 citation statements)

References 34 publications

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“…Previous studies have demonstrated that acivicin has a protective effect on cisplatin-induced nephrotoxicity (Hanigan et al, 1994) and suppresses GGT-dependent oxidative damage in ischemic rat kidney (Cutrín et al, 2000). However, acivicin is known to inhibit irreversibly various glutamine amidotransferases, including imidazole glycerol phosphate synthase and guanine monophosphate synthetase, and inactivate a number of biosynthetic enzymes for purine and pyrimidine, amino acids, and amino sugars, which results in a potent cytotoxicity (Earhart and Neil, 1985;Chittur et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…However, it still remains to be elucidated whether these interventions are also beneficial in clinical cases. Cutrín et al (2000) have reported that short-term kidney ischemia (25 min) increases GGT activity and also enhances lipid peroxidation, suggesting that the postischemic AKI is related to an increase of GGT activity. In fact, acivicin, a prototype of GGT inhibitor (Capraro and Hughey, 1985), could prevent the ischemia-induced increase in GGT activity, lipid peroxidation enhancement, and morphological alterations (Curtin et al, 2000).…”

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confidence: 99%

“…On the other hand, the renal GSH content was markedly elevated by the GGsTop treatment. The rationale for the dose setting of GGsTop in our study is based on findings that the effective dosage of acivicin to exert antioxidative effects is 50 to 300 mg/kg (Slusser et al, 1990;Cutrín et al, 2000) and GGsTop possesses more than 100 times higher activity in inhibiting GGT than that of acivicin (Han et al, 2007). Next, we evaluated how the increase of GGT activity is associated with renal O 2 .…”

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confidence: 99%

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Preventive Effect of GGsTop, a Novel and Selective γ-Glutamyl Transpeptidase Inhibitor, on Ischemia/Reperfusion-Induced Renal Injury in Rats

Yamamoto¹,

Watanabe²,

Hiratake³

et al. 2011

The Journal of Pharmacology and Experimental Therapeutics

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GGsTop [2-amino-4-{[3-(carboxymethyl)phenyl](methyl)phosphono}butanoic acid], is a novel, highly selective, and irreversible ␥-glutamyl transpeptidase (GGT) inhibitor with no inhibitory activity on glutamine amidotransferases. In this study, we investigated the effects of treatment with GGsTop on ischemia/reperfusion-induced renal injury in uninephrectomized rats. Ischemic acute kidney injury (AKI) was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion 2 weeks after contralateral nephrectomy. Renal function in vehicle-treated AKI rats markedly decreased at 1 day after reperfusion. Treatment with GGsTop (1 and 10 mg/kg i.v.) 5 min before ischemia attenuated the ischemia/reperfusion-induced renal dysfunction in a dose-dependent manner. Histopathological examination of the kidney of AKI rats revealed severe renal damage, which was significantly suppressed by the GGsTop treatment. In renal tissues exposed to ischemia/reperfusion, GGT activity was markedly increased immediately after reperfusion, whereas renal superoxide production and malondialdehyde level were significantly increased 6 h after reperfusion. These alterations were abolished by the treatment with GGsTop. In addition, renal glutathione content was decreased by the 45-min ischemia, but its level was markedly elevated by the GGsTop treatment. Our results demonstrate that the novel and highly selective GGT inhibitor GGsTop prevents ischemia/ reperfusion-induced AKI. The renoprotective effect of GGsTop seems to be attributed to the suppression of oxidative stress by inhibiting GGT activation, thereby preventing the degradation of glutathione.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Preventive Effect of GGsTop, a Novel and Selective γ-Glutamyl Transpeptidase Inhibitor, on Ischemia/Reperfusion-Induced Renal Injury in Rats

Yamamoto¹,

Watanabe²,

Hiratake³

et al. 2011

The Journal of Pharmacology and Experimental Therapeutics

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“…Opinion on whether serum uric acid is a true risk factor for mortality and cardiovascular disease, or is simply associated with other risk factors, is divided, but there is no doubt that it is associated with the metabolic syndrome (Liese et al, 1999;Tomita et al, 2000). Serum gammaglutamyl transferase (GGT) has been shown to be prospectively associated with cardiovascular disease (Cutrin et al, 2000;Emdin et al, 2001;Hood et al, 1990;Lee et al, 2006;Pompella et al, 2004;Ruttmann et al, 2005;Wannamethee et al, 1995), hypertension (Lee et al, 2003b;Miura et al, 1994) and diabetes (Lee et al, 2003a;Lee et al, 2003b;Lee et al, 2004;Meisinger et al, 2005;Nakanishi et al, 2003;Perry et al, 1998;Wannamethee et al, 2005;Whitfield, 2001). Serum GGT is significantly correlated with total or LDL cholesterol, high-density lipoprotein (inversely), and particularly with triglycerides (Whitfield, 2001;Whitfield et al, 2002).…”

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confidence: 99%

A Longitudinal Genetic Study of Uric Acid and Liver Enzymes in Adolescent Twins

et al. 2007

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Biochemical traits such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT) and uric acid are associated with obesity, and with risk of cardiovascular disease, metabolic syndrome and diabetes. Each is subject to genetic influences, but little is known about changes in genetic and environmental influences on these traits over time. We investigated the contribution of genetic and environmental influences to variation in these biochemical traits in adolescent twins and their nontwin siblings from 965 twin families. Twins were studied at ages 12, 14 and 16 years. Multivariate genetic models that included effects of age and sex were fitted to determine whether the same or different genetic or environmental factors influence each trait at different ages. Results showed that the genetic factors influencing AST, ALT, GGT and uric acid change over time during adolescence, and that the magnitude of these effects differs between males and females. The nonshared environment effects were generally time specific. There are developmental changes in genes affecting these traits during adolescence.

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“…Aviacin (an inhibitor of GGT) prevented the increase of GGT activity induced by ischemia and protected the ischemic organs and tissues against lipid peroxidation, free radical generation and morphological changes. [15].…”

Section: Discussionmentioning

confidence: 99%

Gamma-Glutamyl Transpeptidase as the Marker of Kidney Graft Function

Kwiatkowska¹,

Domański²,

Bober³

et al. 2014

Adv Clin Exp Med

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Background. Gamma-glutamyl transpeptidase (GGT) is a glycoprotein of the external surface of various cell types. The activity of GGT has been observed in cells and tissues with secretory activity, such as the proximal tubular cells in kidneys. GGT also plays an important pro-oxidant role, stimulating the generation of hydroxyl radicals, and increases membrane lipid peroxidation. Objectives. In this study we examined whether the monitoring of GGT activity in urine may be a prognostic factor of kidney allograft function. The study enrolled 107 Caucasian renal transplant recipients. Material and Methods. Urine samples were collected for GGT and creatinine analysis on the 1 st day after transplantation, and then in the 3 rd and 12 th month. Results. Higher urine GGT activity in the 3 rd month after transplantation was associated with significantly higher risk of graft failure (HR = 1.063 per each U/g creatinine; 95%Cl:1.004-1.127; p = 0.037) in the Cox proportional hazards model. Moreover, there were positive correlations between urine GGT and the grade of interstitial fibrosis (Rs = 0.64, p = 0.01) and tubular atrophy (Rs = 0.54, p = 0.056) in specimens collected in the 3 rd month after transplantation. Conclusions. Our results suggest that higher urine GGT activity in the 3 rd month after transplantation may be a prognostic factor of graft failure (Adv Clin Exp Med 2014, 23, 6, 947-952).

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Contribution of γ glutamyl transpeptidase to oxidative damage of ischemic rat kidney

Cited by 33 publications

References 34 publications

Preventive Effect of GGsTop, a Novel and Selective γ-Glutamyl Transpeptidase Inhibitor, on Ischemia/Reperfusion-Induced Renal Injury in Rats

Preventive Effect of GGsTop, a Novel and Selective γ-Glutamyl Transpeptidase Inhibitor, on Ischemia/Reperfusion-Induced Renal Injury in Rats

A Longitudinal Genetic Study of Uric Acid and Liver Enzymes in Adolescent Twins

Gamma-Glutamyl Transpeptidase as the Marker of Kidney Graft Function

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