Protection by Selenium against Gentamicin-Induced Acute Renal Damage in the Rat1

Ngaha, Edwin O.; Ogunleye, Isaac O.; Madusolumuo, M. A.

doi:10.1093/oxfordjournals.jbchem.a134675

Cited by 11 publications

(8 citation statements)

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“…Ngaha and Ogunleye (1983) showed, in vitro, that GM evokes the labilization of rat kidney lysosomes with the marked release of lysosomal acid hydrolases. In their later work, these researchers confirmed this effect in vivo by measuring urinary excretion of some lysosomal enzymes (Ngaha et al, 1984). Moreover, in both studies, they showed that this GM-induced degradation of the lysosomal membrane could be reduced to a considerable extent by concomitant administration of selenium.…”

Section: Discussionmentioning

confidence: 81%

Protective effect of selenium on gentamicin-induced oxidative stress and nephrotoxicity in rats

Randjelović

Veljković

Stojiljković

et al. 2011

Drug and Chemical Toxicology

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Gentamicin (GM) is a widely used antibiotic against serious, life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of selenium (Se) in GM-induced nephrotoxicity in rats. Experiments were done on 32 adult Wistar rats divided into four groups of 8 animals each. The GM group received gentamicin (100 mg/kg), whereas the GM+Se group received the same dose of GM and selenium (1 mg/kg) by intraperitoneal (i.p.) injections on a daily basis. Animals in the Se group, serving as a positive control, received only selenium (1 mg/kg) and the control group received saline (1 mL/day), both given i.p. All groups were treated during 8 consecutive days. Quantitative evaluation of GM-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of selenium coadministration with GM. GM was observed to cause a severe nephrotoxicity, which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous selenium administration protected kidney tissue against oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by selenium pretreatment. The results from our study indicate that selenium supplementation attenuates oxidative-stress-associated renal injury by reducing oxygen free radicals and lipid peroxidation in GM-treated rats.

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Section: Discussionmentioning

confidence: 81%

Protective effect of selenium on gentamicin-induced oxidative stress and nephrotoxicity in rats

Randjelović

Veljković

Stojiljković

et al. 2011

Drug and Chemical Toxicology

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“…Although there are several reports demonstrating that aminoglycoside antibiotics are nephrotoxic, the underly ing mechanism has not been fully described yet [1,12,19,20,29,30]. The data indicating that some radical scaven gers provide marked functional and histopathological protection against gentamicin toxicity [6,18,19,21,22,[31][32][33] suggest the possibility that the free radical metabo lism in the renal tissue is greatly affected by gentamicin.…”

Section: Discussionmentioning

confidence: 99%

“…The data indicating that some radical scaven gers provide marked functional and histopathological protection against gentamicin toxicity [6,18,19,21,22,[31][32][33] suggest the possibility that the free radical metabo lism in the renal tissue is greatly affected by gentamicin. However, the subject has not been studied in detail until now.…”

Section: Discussionmentioning

confidence: 99%

“…Hydrogen peroxide generated by mitochondria is primarily derived from the superoxide radical [17], These radical species then may generate hydroxyl radicals by the Haber-Weiss reaction [ 18]. Ngaha et al [ 19] reported that selenium, the cofactor of gluta thione peroxidase (GSH-Px), decreased the gentamicininduced nephrotoxicity in rats. This observation has im plicated free radicals and lipid peroxidation in the patho genic mechanism of aminoglycoside nephrotoxicity.…”

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confidence: 99%

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Reduced Enzymatic Antioxidant Defense Mechanism in Kidney Tissues from Gentamicin-Treated Guinea Pigs: Effects of Vitamins E and C

Kavutçu¹,

Canbolat²,

Öztürk³

et al. 1996

Nephron

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In this study, the activities of major enzymes participating in free radical metabolism (xanthine oxidase, XO; CuZn and Mn superoxide dismutases, SOD; glutathione peroxidase, GSH-Px; catalase, CAT) were measured in kidney tissues from guinea pigs treated with gentamicin alone (200 mg/kg/day), gentamicin plus vitamin C (600 mg/kg/day), gentamicin plus vitamin E (400 mg/kg/day), and gentamicin plus vitamins C and E together for 10 days, and from animals treated with physiological saline solution alone during this period. We found no significant differences between control and gentamicin groups with respect to XO and CuZn-SOD activities. However, the activities of Mn-SOD, GSH-Px, and CAT were found to be significantly depressed in the gentamicin-treated group relative to controls. In the gentamicin plus vitamin C group, the renal tissue Mn-SOD activity was found to be higher as compared with control and gentamicin groups. In this group, XO, GSH-Px and CAT activities were also higher than in the gentamicin-treated group, but no statistically significant differences existed between the values of this group and controls. Similar results were also observed in the gentamicin plus vitamin E group for Mn-SOD, GSH-Px, CAT, and XO. In this group, the CuZn-SOD activity was found to be decreased as compared with control and gentamicin groups. In the gentamicin plus vitamins C and E group, the CuZn-SOD activity was found to be decreased, the XO activity to be unchanged, and Mn-SOD, GSH-Px, and CAT activities to be increased as compared with the gentamicin and control groups. The results suggest that the enzymatic antioxidant defense system was significantly disturbed because of the suppressed activities of Mn-SOD, GSH-Px, and CAT in the kidney tissues from animals treated with gentamicin. However, vitamins C and E given concurrently with gentamicin completely abrogated this enzymatic suppression.

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“…Therefore, attempts to prevent these toxic events appear justified. Earlier studies suggested a protective effect of polyaspartic acid (3,15) or selenium (32). However, the clinical relevance of those experimental results remains to be established.…”

mentioning

confidence: 98%

Effects of diltiazem on netilmicin-induced nephrotoxicity in rabbits

Lortholary

Blanchet

Nochy

et al. 1993

Antimicrob Agents Chemother

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Aminoglycoside nephrotoxicity remains a common clinical problem and is the major cause of acute toxic renal failure in hospitalized patients. In recent studies, calcium channel blockers gave controversial results in the prevention of acute ischemic or toxic renal failure. The aims of the study were (i) to describe a rabbit model of mild renal failure (50%o reduction in glomerular filtration rate with a mean value of 1.78 0.46 ml/kg/min) induced by netilmicin given intramuscularly at 20 mg/kg of body weight every 8 h for 5 days, (ii) to investigate the protective effect of diltiazem given at a therapeutic dose (1 mg/kg given intramuscularly every 8 h for 5 days), and (iii) to investigate the mechanisms of this protection through evaluation of function tests, optic histology, and glomerular morphometry. Animals treated with netilmicin and diltiazem exhibited an unchanged glomerular filtration rate compared with controls (3.39 + 0.58 versus 3.68 -0.78 ml/kg/min, respectively). This protective effect was not associated with any change in systemic or renal hemodynamics (i.e., no change in renal plasma flow) or changes in the pharmacokinetics of netilmicin, as assessed by fractional excretion and cortical uptake. Netilmicin-induced tubular toxicity was unchanged by diltiazem. Our results suggest that (i) netilmicin exhibits a toxic effect at both the glomerular and the tubular levels, (ii) diltiazem, a calcium channel blocker, when given at low therapeutic doses, is able to prevent the aminoglycoside-induced renal failure through a potential glomerular mechanism. The precise mechanisms of the protection remain to be elucidated. These results deserve clinical evaluation in high-risk patients. (5,21,24). In models of aminoglycoside toxicity, contradictory results have been published. Calcium channel blockers have been reported to be of no use (9,18,43), to exhibit a deleterious effect (17), or again, to be efficient (25, 35) in * Corresponding author. preventing renal failure. In those studies in rats, aminoglycoside and calcium channel blocker doses were high and gentamicin, one of the most nephrotoxic aminoglycosides, was frequently used.We have observed, in human volunteers, that diltiazem (60 mg given three times a day for 7 days) could prevent the increase in urinary N-acetylglucosaminidase (NAG) levels and the loss of dilution ability induced by netilmicin (4.5 mg/kg of body weight given once daily for 7 days) (30). However, in studies performed in humans, it is difficult to investigate the precise mechanisms of such protective effects (37).The aims of the present study were (i) to describe a rabbit model of moderate renal failure induced by netilmicin at the lowest dose that induced a toxic effect (a regimen of three injections per day was chosen to increase the toxic potential over a short period of time [5 days]), (ii) to investigate the protective effect of diltiazem given at therapeutic doses, and (iii) to elucidate at which level protection could occur.Both drugs were chosen because they have previously bee...

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Protection by Selenium against Gentamicin-Induced Acute Renal Damage in the Rat1

Cited by 11 publications

References 0 publications

Protective effect of selenium on gentamicin-induced oxidative stress and nephrotoxicity in rats

Protective effect of selenium on gentamicin-induced oxidative stress and nephrotoxicity in rats

Reduced Enzymatic Antioxidant Defense Mechanism in Kidney Tissues from Gentamicin-Treated Guinea Pigs: Effects of Vitamins E and C

Effects of diltiazem on netilmicin-induced nephrotoxicity in rabbits

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