Gentamicin-Induced Nephrotoxicity in Rats Ameliorated and Healing Effects of Resveratrol

Silan, Coşkun; Uzun, Orhan; Çomunoglu, Nil Üstündag; Gökçen, Sanem; Bedirhan, Selma; Cengiz, Müjgan

doi:10.1248/bpb.30.79

Cited by 81 publications

(59 citation statements)

References 40 publications

(26 reference statements)

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“…These results could be in accord with several other researches, which reported that, compounds with antioxidant properties like S-allylmercaptocysteine 40) and diallyl sulfide 41) inhibited the increased urinary excretion of total protein induced by GM in rats. Other compounds like resveratrol, 22) carnosine 23) or garlic extract, 8) partially prevented the increase in BUN and serum creatinine levels induced by GM. In the present study, the role of ROS in GM-induced nephrotoxicity was assessed by the usage of antioxidant agent, quercetin, and further evaluation of alterations in the biochemical indicators of oxidative stress mainly GSH, TBARS levels, SOD and CAT activities beside histological changes.…”

Section: Discussionmentioning

confidence: 95%

“…Results from many studies 22,23,40) have shown that GM produced an elevation in the concentrations of biochemical indicators of kidney function such as BUN, serum creatinine and total protein excretion in urine. Consistent with the data from the study of Pedraza-Chaverrí et al 40) we observed in our study that urinary excretion of total protein was increased after GM injection indicating tubular damage.…”

Section: Discussionmentioning

confidence: 99%

“…This result is confirmed by other studies, which have pointed to reduction of GSH levels after GM administration. 22,23) An explanation to GSH depletion after GM treatment is increased consumption of GSH in non-enzymatic removal of oxygen-radicals. In addition, oxidation of GSH to GSSG by the oxidant stress, with efflux of GSSG being the major factor responsible for maintenance of the redox ratio.…”

Section: Discussionmentioning

confidence: 99%

“…Cellular swelling is the first manifestation of these reversible changes which can be detected under light microscope. 22) Swelling of endothelium lining the glomerular tufts and tubular vacuolization is the reflection of these reversible changes in kidneys. 54) In gentamicin group, we have observed swelling of endothelium lining the glomerular tufts and vacuolization in all samples.…”

Section: Discussionmentioning

confidence: 99%

“…21,12) Quercetin was dissolved in ethanol and then diluted with tap water to the required concentration for oral administration. Group 3: Rats in this group were injected intraperitoneally with 80 mg/kg/d of gentamicin sulfate for 7 d. 22,23) Group 4: Rats in this group were simultaneously treated with the same previous doses of quercetin and gentamicin for 7 d. Total protein levels were estimated in 24-h urine samples every other day. The rats were sacrificed on the seventh day; blood samples were collected into tubes and allowed to clot at room temperature.…”

Section: Drugs and Chemicalsmentioning

confidence: 99%

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Protective Effect of Quercetin against Gentamicin-Induced Nephrotoxicity in Rats

Abdel-Raheem

Abdelghany

Mohamed

2009

Biological & Pharmaceutical Bulletin

152

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Gentamicin (GM) is an antibiotic widely used in treating severe gram-negative infections. However, its clinical use is limited by its nephrotoxicity. Several lines of evidence indicate that free radicals are important mediators of gentamicin nephrotoxicity. Therefore, the aim of this work was to investigate the possible protective effect of the flavonoid quercetin, an antioxidant, on gentamicin-induced nephrotoxicity. For this purpose, rats were divided into four groups. First group served as a control and injected with the normal saline, second group was injected with quercetin (50 mg/kg/d, per os) for 7 d, third group was injected with gentamicin (80 mg/kg/d, intraperitoneally) for 7 d and the fourth group of animals was injected with quercetin plus gentamicin simultaneously for 7 d. Total protein levels were estimated in 24-h urine samples to assess kidney dysfunction. The rats were sacrificed on the seventh day and kidneys were collected for histopathological studies. Blood urea nitrogen (BUN) and creatinine levels were measured in the blood. Moreover, glutathione (GSH), lipid peroxide (TBARS) levels, superoxide dismutase (SOD) and catalase (CAT) activities were determined in renal tissues. GM-treated rats showed early kidney dysfunction as urinary total protein, BUN and serum creatinine levels were significantly increased. The significant decrease in GSH levels, SOD, CAT activities and increase in TBARS levels, indicated that GMinduced nephrotoxicity was mediated through oxidative stress reactions. Histopathological examination of GM-treated rats revealed degenerative changes in glomeruli and tubules. On the other hand, simultaneous administration of quercetin plus gentamicin protected kidney tissues against nephrotoxic effects of gentamicin as evidenced from amelioration of histopathological changes and normalization of kidney biochemical parameters.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Drugs and Chemicalsmentioning

confidence: 99%

See 3 more Smart Citations

Protective Effect of Quercetin against Gentamicin-Induced Nephrotoxicity in Rats

Abdel-Raheem

Abdelghany

Mohamed

2009

Biological & Pharmaceutical Bulletin

152

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Candesartan and epigallocatechin‐3‐gallate ameliorate gentamicin‐induced renal damage in rats through p38‐MAPK and NF‐κB pathways

Ahmed

Mohamed

2018

J Biochem & Molecular Tox

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This study pointed to estimate the possible protective impacts of candesartan and/or epigallocatechin‐3‐gallate (EGCG) against gentamicin‐induced nephrotoxicity. The current work revealed that gentamicin significantly elevated relative kidney weight and the serum level of creatinine and urea. Also, renal level of malondialdehyde was significantly increased with a concurrent decrease in renal glutathione‐S‐transferase and superoxide dismutase activities. Moreover, renal levels of nuclear factor‐kappa B (NF‐κB) and p38 mitogen‐activated protein kinase (p38‐MAPK) were increased together with the elevation of tumor necrosis factor‐alpha and interleukin‐1 beta levels after gentamicin treatment. In addition, caspase‐3 expression was elevated, and histological examination revealed extreme alterations enlightening inflammation, degeneration, and necrosis. Pretreatments with candesartan and/or EGCG attenuated gentamicin‐induced nephrotoxicity. Importantly, the altered expression of p38‐MAPK and NF‐κB may play a significant role in the protective mechanisms exerted by candesartan and EGCG. Coadministration of candesartan and EGCG exhibited more profound response compared with the monotherapy.

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Effects of resveratrol on drug- and carcinogen-metabolizing enzymes, implications for cancer prevention

Guthrie

Chow

Martinez

2017

Pharmacol Res Perspect

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Resveratrol is a polyphenol found in grape skins and peanuts that has demonstrated many health benefits including protection against aging, cardiovascular and metabolic disease, neurological decline, and cancer. The anticancer properties of resveratrol have been attributed to a variety of mechanisms, including its general inhibition of phase I metabolism and induction of phase II metabolism. The effects of resveratrol on these enzymes, however, are still unclear, as in vitro evidence often contrasts with animal studies and clinical trials. Reasons for these variances could include the low bioavailability of resveratrol and the effects of resveratrol metabolites. Due to resveratrol's interactions with drug‐metabolizing enzymes and drug transporters, individuals concurrently taking pharmacological doses of resveratrol with other supplements or medications could potentially experience nutrient‐drug interactions. This review summarizes the known effects of resveratrol and its main metabolites on drug metabolism in order to help characterize which populations might benefit from resveratrol for the prevention of cancer, as well as those that may need to avoid supplementation due to potential drug interactions.

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Gentamicin-Induced Nephrotoxicity in Rats Ameliorated and Healing Effects of Resveratrol

Cited by 81 publications

References 40 publications

Protective Effect of Quercetin against Gentamicin-Induced Nephrotoxicity in Rats

Protective Effect of Quercetin against Gentamicin-Induced Nephrotoxicity in Rats

Candesartan and epigallocatechin‐3‐gallate ameliorate gentamicin‐induced renal damage in rats through p38‐MAPK and NF‐κB pathways

Effects of resveratrol on drug- and carcinogen-metabolizing enzymes, implications for cancer prevention

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