The effect of grape seed proanthocyanidin extract in preventing amikacin-induced nephropathy.
ABSTRACT Nephrotoxicity induced by aminoglycosides (AGs) limits their clinical use. As yet, no molecules have been approved to prevent AG nephropathy. We aim to investigate the effectiveness of grape seed proanthocyanidin extract (GSPE) in the prevention of amikacin (AK)-induced nephrotoxicity.
A total of 24 rats were allocated into control, GSPE, AK, and AK + GSPE groups. While 1 mL saline was administered for 6 days in control and AK groups, 100 mg/kg GSPE was administered in GSPE and AK + GSPE groups. On day 7, intraperitoneal (i.p.) saline was administered in control and GSPE groups, while 1.2 g/kg i.p. AK was administered in AK and AK + GSPE groups. The experiment was terminated on day 9. Blood samples were taken for the measurement of renal functions. Renal tissues of the rats were removed for the analysis of malondialdehyde (MDA), total oxidant system (TOS), total antioxidant system, oxidative stress index (OSI), and for histopathological examination.
MDA level was found to be lower in GSPE group compared with other study groups. There was significantly more renal histopathological damage and higher blood urea nitrogen, creatinine, TOS, OSI, and MDA levels in the AK group compared with the control and AK + GSPE groups. The same parameters showed significant improvement in AK + GSPE group compared with AK group.
Our findings demonstrate for the first time that GSPE reduces oxidative damage in AK nephropathy and provides biochemical and renal histopathological improvements.
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ABSTRACT: Aim: The purpose of this study was to assess the role of caspase-dependent apoptosis, caspase 1, calpain 1, inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) and the protective effect of grape seed proanthocyanidin extract (GSPE) in the development of rhabdomyolysis-induced acute kidney injury (AKI). Materials and Methods: Twenty-one rats were divided into 3 groups - control, rhabdomyolysis and rhabdomyolysis + GSPE. Rhabdomyolysis was induced in the rhabdomyolysis and rhabdomyolysis + GSPE groups with the injection into both hind limbs of 10 ml/kg hypertonic (50%) glycerol following 24-hour dehydration on the 6th day. The rhabdomyolysis + GSPE group was given GSPE at 100 mg/kg by gavage for 7 days. The experiment was concluded 48 h after glycerol injection. Blood specimens were collected, and kidney tissues were extracted for histopathological examination. Results: We identified an increase in blood urea nitrogen, creatinine, histopathological score, iNOS, caspase 3, caspase 1 and calpain 1 expression in the rhabdomyolysis group compared to the controls and a decrease in eNOS expression. In the rhabdomyolysis + GSPE group, however, there was a decrease in these mediators, together with an increase in eNOS expression. Conclusion: This study shows for the first time in the literature that calpain 1 is involved in the pathogenesis of rhabdomyolysis-induced AKI, and that GSPE may have a renoprotective effect. © 2013 S. Karger AG, Basel.American Journal of Nephrology 10/2013; 38(5):368-378. DOI:10.1159/000355537 · 2.65 Impact Factor
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ABSTRACT: Aim: Colistin is an old antibiotic used in the treatment of gram negative infections. It was once suspended because of its nephrotoxic effect, but has since been reintroduced due to multi-drug resistant bacterial infections. The pathogenesis of colistin-associated nephropathy has not been clarified, and there is currently no effective therapeutic or prophylactic agent available. The aim of this study was to investigate the role of caspase-associated apoptosis, caspase 1, calpain 1, iNOS and eNOS expression in the pathogenesis of colistin-associated nephrotoxicity and the effect of grape seed proanthocyanidin extract (GSPE) in preventing it.Materials-Methods: 24 rats were divided into three groups; control, colistin and colistin+GSPE. Colistin-associated nephropathy was induced by the administration of 300,000 IU/kg/day colistin intraperitoneally for seven days. The experiment was discontinued on the seventh day. Blood was collected for BUN and creatinine measurement. Histopathological examination of kidney tissue and caspase 1 and 3, iNOS, eNOS, TUNEL and calpain 1 staining was also performed.Results: A significant increase in BUN, creatinine, renal histopathological score, TUNEL, caspase 1, 3, calpain 1, iNOS and eNOS was observed in the colistin group compared to the control group. A significant decrease in BUN, creatinine, renal histopathological score, TUNEL, caspase 1, 3, calpain 1, iNOS and eNOS was observed in the colistin+GSPE group compared to the colistin group.Conclusion: Our study shows, for the first time in the literature, that caspase-mediated apoptosis, iNOS, caspase 1 and calpain 1 are involved in the pathogenesis of colistin-associated nephropathy. GSPE had a renoprotective effect, as shown by these lowered mediators.Antimicrobial Agents and Chemotherapy 04/2013; 57(8). DOI:10.1128/AAC.00343-13 · 4.45 Impact Factor