The Effect of Grape Seed Proanthocyanidin Extract in Preventing Amikacin-Induced Nephropathy

Department of Nephrology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey.
Renal Failure (Impact Factor: 0.94). 01/2012; 34(2):227-34. DOI: 10.3109/0886022X.2011.643391
Source: PubMed


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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    • "ROS are known to mediate cascade processes leading to tissue damage in the kidney tubules. Several plant polyphenols , known to have antioxidant activity, have shown ameliorative effects on the AK induced nephrotoxicity [31], cisplatin nephrotoxicity [4] and oxytetracycline toxicity [1]. Virgin olive oil and more recently, the olive leaves were shown to be rich in antioxidant polyphenols such as oleuropein, verbascoside , ligstroside, tyrosol and hydroxytyrosol [11]. "
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    ABSTRACT: Amikacin is an important antibiotic, and its use is limited because of the induced nephrotoxicity. Thus, search for natural and synthetic agents that can moderate amikacin toxicity never stopped. The present study aims to investigate the possible ameliorative effects of virgin olive oil and olive leaf extract against the amikacin-induced nephrotoxicity in rat. Methods: 48 rats were distributed into 6 groups: 1-Animals of control (C) group were injected intraperitoneally (ip) with saline, 2-(AK); injected ip with amikacin {300. mg/kg/day for 12days}, 3-(OO) group: given olive oil {7. ml/kg/day for 16days}, 4-(OOAK) group: given olive oil as in OO and amikacin for 12days, 5-(OL) group: given olive leaf extract {50. mg/kg/day for 16days}, 6-(OLAK) group: given leaf extract as in OL and amikacin for 12days. Animals were fasted and sacrificed. Serum was used for biochemical analysis and kidneys for histopathology. Results: Serum urea and creatinine were significantly (P<. 0.001) elevated in AK, and significantly dropped in the OOAK and OLAK groups. Serum uric acid was reduced in AK by 45.29%. Kidneys from AK showed necrosis, whereas, those from OOAK and OLAK showed mild histology. The serum triglyceride was decreased by 17.8% in OL, by 37.02% in OOAK and by 31.48% in OLAK. The calculated amikacin effect showed a significant positive correlation with urea (r=0.521, P=0.0004), and a negative correlation with uric acid (r=-0.58, P< 0.0001). Conclusion: The study confirmed nephrotoxicity of amikacin in rat which was ameliorated by virgin olive oil and by olive leaf extract. Amikacin did not cause dyslipidemia but reduced serum uric acid.
    Full-text · Article · Sep 2015 · Toxicology Reports

  • No preview · Article · Jan 2013 · Iranian journal of kidney diseases
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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.
    Full-text · Article · Apr 2013 · Antimicrobial Agents and Chemotherapy
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