Effects of cisplatininduced nephrotoxicity on gentamicin. Abstract objective to evaluate nephroprotective potential of solanum xanthocarpum s. Protective effects of cilastatin against vancomycin. Pinocembrin attenuates gentamicininduced nephrotoxicity. The defensive effects of hesperidin hdn, a bioflavonoid was investigated on gentamicin gen provoked nephrotoxicity in rats. Apr 18, 2019 dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position. Effects of cosupplementation of vitamins e and c on. Gentamicin is a very effective antibiotic in treating gramnegative bacterial infection in both humans and animals. Nephrotoxic effects of aminoglycosides on the developing kidney. Mechanisms of antimicrobialinduced nephrotoxicity in.
Aminoglycoside antibiotics, in particular gentamicin and tobramycin, are still commonly used in paediatric clinical practice. Nephrotoxicity was induced in rats by intraperitoneal injection i. Acute tubular necrosis due to ischemia or other insults and the pathogenesis and potential therapy of aminoglycoside nephrotoxicity are discussed separately. Greater care is required in people with myasthenia gravis and other neuromuscular disorders as there is a risk of worsening weakness. Gentamicin induced nephrotoxicity ranges between 8% and 26%, while by audiometry about 25% of patients on aminoglycoside therapy develop ototoxicity. Oxidative stress due to abnormal production of reactive oxygen species has been implicated in the nephrotoxicity induced by gentamicin. Gentamicin induced nephrotoxicity is a models of acute renal failure caused by oxidative stress generated through. Nephrotoxicity due to a aminoglycosides b cyclophosphamide c cisplatin d radiocontrast e analgesic f. Apart from their beneficial effects, aminoglycosides induce nephrotoxicity in 1020% of therapeutic cases. The effects of cisplatin induced nephrotoxicity on the pharmacokinetics of a renally excreted antibiotic, gentamicin, were studied in f344 rats.
Along with the use of ag antibiotics is the associated renal insufficiency complication. Gentamicin should not be used if a person has a history of hypersensitivity, such as anaphylaxis, or other serious toxic reaction to gentamicin or any other aminoglycosides. Serum concentrations of aminoglycosides should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels. In addition, based on the experimental and clinical studies, the possible therapeutic approach to prevent gentamicin induced nephrotoxicity has been discussed. Recent epidemiological studies, using more widely accepted. Pdf in this study, we aimed to investigate the possible protective effect of resveratrol on gentamicin induced nephrotoxicity. Extract ameliorates gentamicininduced nephrotoxicity associated oxidative stress, inflammation, and apoptosis in rodent model alia. Bennett, md division of nephrology, hypertension, and clinical pharmacology oregon health sciences university portland, oregon, usa the kidney is the major site of damage from many drugs and chemicals that are used in. The kidneys are susceptible to oxidant induced injury due their high reliance on mitochondria and atp to facilitate the transport function of the nephron. The uk national institute of health and care excellence nice. Gentamicin gm induced nephrotoxicity may be sex hormones related.
The nephroprotective effect of aqueousethanolic extract of moringa oleifera leaves 150 and 300 mgkg was evaluated against gentamicin induced 80 mgkg renal injury in rabbits. Risk factors for nephrotoxicity in patients treated with aminoglycosides were determined from the case records of 214 patients in two prospective, randomized clinical trials of gentamicin and tobramycin. As such, the mechanisms of oxidant induced injury have been a focus of nephrotoxicity for decades. Gentamicininduced acute renal failure model creative biolabs. Aminoglycosideinduced nephrotoxicity in children pdf.
Edwards, pharmd, bcps, cgp journal of pharmacy practice 2014 27. The 6rs of drug induced nephrotoxicity bmc nephrology. Protective effect of crocin on gentamicininduced nephrotoxicity in rats. The urban cf study urinary biomarkers of aminoglycoside induced nephrotoxicity in children with cystic fibrosis received ethical approval from. Drug induced nephrotoxicity is an important cause of renal failure in dogs. Aminoglycoside antibiotics, such as gentamicin, can produce nephrotoxicity in dogs, due to in part to an imbalance of pro and antioxidants oxidative stress. Aminoglycosideinduced nephrotoxicity indiana university. This is especially true of the proximal tubule cells. Lerner sa, schmitt ba, seligsohn r, matz g comparative study of ototoxicity and nephrotoxicity in patients randomly assigned to treatment with amikacin or gentamicin.
Qadir and others published gentamicin induced nephrotoxicity in albino mice. Elmougy1 1department of veterinary medicine, faculty of agriculture and veterinary medicine, alqaseem university, buraydah. Pioglitazone attenuates kidney injury in an experimental model of. However, aminoglycosides are to be used only when there is a definite indication and for the minimum duration required. Nephroprotective action of phoenix dactylifera in gentamicin induced nephrotoxicity a. Almassarani, 1 ajazahmad, 5 mohamedhefnawy, 6 mohammedalyahya, 1 omera. A number of crude herbal extracts have been reported to ameliorate gentamicin induced nephrotoxicity. Androgenandrogen receptor affects gentamicin induced nephrotoxicity through regulation of megalin expression author links open overlay panel elsayed g. Gentamicin induced nephrotoxicity was indicated by the reduced renal. Mar 03, 2016 pdf 761 k pdf plus 422 k citing articles.
N2 aminoglycosides remain critical antibiotics in the armamentarium for serious gramnegative bacterial infections despite their wellknown risk for nephrotoxicity and ototoxicity. Aminoglycoside induced kidney injury has been well described and studies show that up to 33% of children exposed to aminoglycosides will develop aki. Van induced nephrotoxicity has been reported to occur in 525% of patients 2, 8, although this incidence can rise to 20 35%, with a consequent increase in. Elsakka a ahmad mohamed elsisi a b osama abd almotaal mansour a bakheet e. Current evidence shows that aminoglycosides do retain activity against the majority of gramnegative clinical bacterial isolates in many parts of the world. Aminoglycosides are concentrationdependent, bactericidal agents that undergo active transport into the cell where they inhibit protein synthesis on the 30s subunit of the bacterial ribosome. Manifestations of and risk factors for aminoglycoside. Gentamicin treatment also stimulated nrf2, ho1, and. Protective effect of apocynin against gentamicininduced. Pioglitazone attenuates kidney injury in an experimental. Jun 19, 2019 see pathogenesis and prevention of aminoglycoside nephrotoxicity and ototoxicity. Aminoglycosides preferentially affect the proximal tubular cells. Pathophysiologic mechanisms of selected types of nephrotoxicity.
Nov 15, 2016 aminoglycoside antibiotics, in particular gentamicin and tobramycin, are still commonly used in paediatric clinical practice. Protective effect of metformin against gentamicin induced nephrotoxicity in rabbits ayesha janjua1, akbar waheed 2 and salman bakhtiar2 1department of pharmacology, foundation university medical college, islamabad, pakistan 2department of pharmacology, army medical college, rawalpindi, pakistan. Pdf effect of silymarin and vitamin e on gentamicin. Effects of pentoxifylline on gentamicininduced nephrotoxicity. Protective effect of montelukast which is cysteinylleukotriene receptor antagonist on gentamicininduced nephrotoxicity and oxidative damage in rat kidney. Inhibitory effect of olive leaf extract on gentamicin. Nephroprotective action of phoenix dactylifera in gentamicin. Aminoglycoside nephrotoxicity kidney international. The effect of fleroxacin on gentamicininduced nephrotoxicity was evaluated with female spraguedawley rats. The effects of sex hormones on gm induced nephrotoxicity in gonadectomized rats were investigated. Saeed mehrzadi, a seyed kamran kamrava, b banafshe dormanesh, c manijeh motevalian, a azam hosseinzadeh, a seyed mohammad taghi hosseini tabatabaei, d habib ghaznavi e. The manifestations of and risk factors for aminoglycoside nephrotoxicity are discussed separately. Pinocembrin attenuates gentamicininduced nephrotoxicity in.
Combinational effect of curcumin and metformin against. Pdf gentamicin induced nephrotoxicity in albino mice. In patients receiving gentamicin for 3 to 5 days, nephrotoxicity occurs in 10% to 25% of the cases. Gentamicin, an aminoglycoside antibiotic with a wide spectrum of activities, is vastly used in the treatment of gramnegative bacterial infections. Still, the relatively frequent occurrence of nephrotoxicity and ototoxicity during aminoglycoside treatment makes physicians reluctant to use these compounds in everyday practice.
Alsaid, 1 mohammadraish, 3 mohammedalsohaibani, 4 shazam. Influence of iron, deferoxamine and ascorbic acid on gentamicin induced nephrotoxicity in rats. Monitoring of drug levels and for toxicity is recommended. Melatonin synergistically enhances protective effect of atorvastatin against gentamicininduced nephrotoxicity in rat kidney. Most of the studies available in veterinary medicine in which nephrotoxicity of aminoglycosides has been studied are based on experimental models of acute renal injury caused by the administration of high doses of gentamicin. Gentamicin gm is an antibiotic related to aminoglycoside group that is used in treating gram. However, treatment with gentamicin is considered to be limited as it induces an oxidative stress. Protective effect of moringa oleifera leaves against. Risk factors for nephrotoxicity in patients treated with.
Nephrotoxicity, defined as a 50% or greater fall in calculated creatinine clearance, developed in 30 patients 14. Effect of superoxide dismutase treatment on gentamicin nephrotoxicity in rats. Pdf histopathological evaluation of nephroprotective effect. There have been several factors previously reported as increasing the risk of nephrotoxicity. Androgenandrogen receptor affects gentamicininduced. Therefore, the goal of our study was to investigate the effects of pioglitazone on kidney injury in an experimental model of gentamicin induced nephrotoxicity in rats. The issue of serumlevel monitoring is discussed relative to the development of nephrotoxicity. Dec 27, 2019 aminoglycosides preferentially affect the proximal tubular cells. Pdf gentamicininduced nephrotoxicity in rats ameliorated and. Studies of risk factors for aminoglycoside nephrotoxicity craig r. The aim of this study was to compare the nephrotoxic potential of amikacin ak and gentamicin gm in patients with normal baseline renal function. Studies of risk factors for aminoglycoside nephrotoxicity.
These drugs cause nephrotoxicity, which particularly affects the proximal tubule epithelial cells due to selective endocytosis and accumulation of aminoglycosides via the multiligand receptor megalin. Patient and drugrelated risk factors are discussed to help identify patients at increased risk. Specifically, gentamicin induced nephrotoxicity model is mostly used to evaluate in vivo nephroprotective activity of natural compounds. Methods twentyfour wistar rats were divided into four groups n6. Nephroprotective activity of solanum xanthocarpum fruit. Lietman, md, phd the epidemiology of aminoglycoside induced nephrotoxicity is not.
Gentamicininduced nephrotoxicity is functionally characterized by an increase in serum creatinine and blood urea nitrogen, incidences of albuminuria and urinary losses of carnitine, decrease in glomerular filtration rate, and renal dysfunction. Aminoglycosideinduced nephrotoxicity in children springerlink. The main concerns with the use of aminoglycoside antibiotics are nephrotoxicity and ototoxicity. Aminoglycosides are among the oldest antibiotics available to treat serious infections caused by primarily, gramnegative bacteria.
Our current knowledge of drug induced kidney disease is. To evaluate the nephroprotective effect of trichosanthes dioica roxb. Protective effect of metformin against gentamicin induced. Aminoglycosides are known to cause nephrotoxicity, ototoxicity, and, more rarely, neuromuscular blockade. Attenuation of gentamicininduced nephrotoxicity in rats by. The cessation of the treatment allows a recovery to control values within approximately 8 days. Gentamicin induced nephrotoxicity was indicated by the reduced renal function and renal oat3 function and expression. Nephrotoxicity induced by gentamicin is a complex situation characterized by an increase in blood urea nitrogen bun and serum creatinine concentration, and tubular necrosis. See pathogenesis and prevention of aminoglycoside nephrotoxicity and ototoxicity. We performed a retrospective observational study to examine this and the predictive value of rifle stage on patient outcome in this setting. Melatonin synergistically enhances protective effect of. Mar 31, 2015 molecular mechanism of drug induced nephrotoxicity 1.
Aminoglycosides have long been one of the commonest causes of drug induced nephrotoxicity. Gentamicin induces renal morphopathology in wistar rats scielo. The plant extract of rhazya stricta has been noted to dosedependently increase the superoxide dismutase activity and the reducedform of glutathione and subsequently decrease lipid peroxides in the renal cortex of gentamicin administered rats. Although aminoglycoside induced nephrotoxicity has been the subject of multiple studies, the short and longterm effect of aminoglycosides administration on the developing kidney of the fetus or premature newborn has not yet been determined. Gentamicin induced nephrotoxicity 585 gentamicin for 8 days, mgkg fig. Aminoglycoside induced ototoxicity is usually irreversible. Concurrent use of other potentially neurotoxic or nephrotoxic agents, or potent diuretics should be avoided. Prospective cohort studies of aki have documented the frequency of drug induced nephrotoxicity to be approximately 1426% in adult populations. Although derangements of lysosomal, mitochondrial, and plasma mem brane structure and bction have been proposed l, the precise mechanisds of genta micin nephrotoxicity remains unknown. However, proposed pathological mechanisms include induction of.
The 6rs of drug induced nephrotoxicity linda awdishu1,2 and ravindra l. Aminoglycosides have long been one of the common causes of drug induced nephrotoxicity. Diagnosis and treatment aminoglycoside nephrotoxicity typically is associated with nonoliguric acute renal failure, that is, azotemia in the presence. Nephrotoxicity induced by aminoglycosides manifests clinically as nonoliguric renal failure, with a slow rise in serum creatinine and a hypoosmolar urinary output developing after several days of treatment. Mehta2 abstract drug induced kidney injury is a frequent adverse event which contributes to morbidity and increased healthcare utilization. A single dose of gentamicin 30 mgkg, iv was given to different groups of rats alone, at the same time as, or on day 4, 7, 15, or 29 following cisplatin administration 6 mgkg, iv. Structural latency of lysosomal nacetyl3glucosaminidasefollowing gentamicin treatment mean of four independent experiments sem. Although a clear recognition of the patient and treatmentrelated risk factors, combined with the onceaday schedule and effective monitoring procedures, have definitely improved the situation over what prevailed in the early 1980s, we are still short of having brought the safety of.
Nephrotoxicity is largely reversible and its incidence is also low in children. The mechanisms of gentamicin induced nephrotoxicity are not completely known. Aminoglycoside antibiotics, such as gentamicin, can produce nephrotoxicity in dogs, due to in part to an imbalance of pro. Nephrotoxicity induced by gentamicin represents a complex phenomenon. Finally, gentamicin nephrotoxicity is potentiated by magnesium depletion 27.
Gentamicininduced nephrotoxicity kidney international. The expression patterns of nuclear factor erythroidderived 2like 2 nrf2, nuclear factor. A prospective comparative study of gentamicin and amikacin. The incidence of gentamicin associated acute kidney injury aki as defined by the rifle criteria is unknown. Nephrotoxicity is a significant concern in pediatrics with 16% of hospitalized aki events being attributable primarily to a drug 4. We have examined the role of reactive oxygen metabolites rom in gentamicin nephrotoxicity and in glycerol induced acute renal failure, a model for myoglobinuric acute renal failure. Pdf hesperidin protects gentamicininduced nephrotoxicity. The most commonly utilized parenteral agents in this class include gentamicin, tobramycin and amikacin. As the use of aminoglycosides became more widespread, the toxic effects of these agents, most notably ototoxicity and nephrotoxicity, became more apparent.
Gentamicin, at doses of 50 or 100 mgkg body wt administered daily to healthy male mf1 mice by i. Nephrotoxicity is the side effect that most limits the dose of van, particularly in patients receiving high doses or combinations with other antibiotics, such as aminoglycosides 7. Our current knowledge of drug induced kidney disease is limited due to varying definitions of kidney injury, incomplete assessment of concurrent risk factors and lack of long term outcome reporting. Electronic surveillance presents a powerful tool to identify susceptible. Aug 08, 2016 nephrotoxicity was induced in rats by intraperitoneal injection i. Drug induced kidney injury is a frequent adverse event which contributes to morbidity and increased healthcare utilization. These agents are freely filtered by the glomeruli and quickly taken up by the proximal tubular epithelial cells, where they are incorporated into lysosomes after first interacting with phospholipids on the brush border membranes. Effects of pentoxifylline on gentamicininduced nephrotoxicity belde kasap 1, mehmet tu. Serum urea and creatinine levels were evaluated as the markers of renal. Pdf histopathological evaluation of nephroprotective.
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