Gentamicin, at doses of 50 or 100 mgkg body wt administered daily to healthy male mf1 mice by i. The aminoglycoside antibiotic gentamicin was selec ted as the test article in this study as it is known to induce acute kidney injury in dogs, a phenomenon which match es the gentamicin related to human pathology and clinical scenario 2. To investigate the role of oxidative stress in gentamicininduced nephrotoxicity and its prevention by using antioxidant vitamin c in wistar albino rats. To evaluate histopathological changes of gentamicin induced nephrotoxicity in rabbits receiving the combination of ciprofloxacin and gentamicin compared with rabbits receiving gentamicin alone. The aim of this study was to evaluate the inhibitory effect of ole on gentamicin induced nephrotoxicity in rats. Gentamicininduced nephrotoxicity in a patient with. In patients receiving gentamicin for 3 to 5 days, nephrotoxicity occurs in 10% to 25% of the cases.
Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first. 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. Effect of cyclooxygenase inhibitors on gentamicininduced. Rats were injected with gentamicin at doses of 20, 40 and 80 mgkg per day for 6 consecutive days. Comparative nephrotoxicity of ribostamycin and gentamicin. Research article gentamicin induced hepatorenal toxicity. Experiments were carried out in male wistar rats weighing 200250 g. Aminoglycosides are able to cross the placental barrier, and may cause nerve or nephrotoxic effects to the fetus. Vitamin e protection against gentamicininduced nephrotoxicity in rats. Effect of superoxide dismutase treatment on gentamicin nephrotoxicity in rats.
We studied gentamicin susceptibility of kidneys infected with e. Gentamicin is an aminoglycoside antibiotic, which induces renal tubular necrosis in rats. Several parameters of renal function, histological changes on light and electron microscopy, and drug levels in renal parenchyma were com. A number of crude herbal extracts have been reported to ameliorate gentamicininduced nephrotoxicity. Protective effect of metformin against gentamicin induced. The development of multidrug resistance among bacteria has now lead clinicians to reexamine the role of the aminoglycosides in the treatment of serious infections. The present study was designed to determine the protective effect of salicylic acid sa in gentamicininduced nephrotoxicity in rats. In the context of the european innomed predtox project, transcriptomic and proteomic studies were performed to provide new insights into the molecular mechanisms of gentamicininduced nephrotoxicity. Diagnosis and treatment aminoglycoside nephrotoxicity typically is associated with nonoliguric acute renal failure, that is, azotemia in the presence. The female spraguedawley rats were randomly allocated to two groups of 9 animals each for timed treatment once daily either 2 h ours a fter l ights o n 2 halo, termed the diurnal group, or 2h after lights off 14 halo, termed the nocturnal group, to assess treatmenttime differences in the time course and extent of both gentamicin induced global measures of toxicity. 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. In conclusion, our results indicate that gentamicin. We investigated this property for a new diuretic, muzolimine, in female wistar rats.
Flavocoxid attenuates gentamicininduced nephrotoxicity in rats. Pdf gentamicin induced nephrotoxicity in albino mice. Twenty four healthy male wistar rats, weighing between 220 260grams, were divided into three groups. Protective effect of bauhinia purpurea on gentamicin induced. Multiple factors may increase the nephrotoxic potential of aminoglycosides. A central aspect of gentamicin nephrotoxicity is its tubular effect, which may range from a mere loss of the brush border in epithelial cells to. Bauhinia purpurea, gentamicin, nephrotoxicity, fruit juice and ethanol. These in vitro observations have been supported by in vivo studies in which scavengers of reactive oxygen metabolites and iron chelators have shown to be protective in gentamicin induced acute renal failure. Gentamicin induces nephrotoxicity in corresponding author. The most important side effect of this drug is nephrotoxicity 3 which is accompanied with elevating blood urea nitrogen bun and creatinine cr levels in serum 4, 5. Histological modifications compatible with gentamicin nephrotoxicity were more persistent in the infected treated animals. Pathophysiologic evidence of gentamicin nephrotoxicity in.
The treatment caused nephrotoxicity as evidenced by doserelated increases in serum creatinine concentration and renal tubular necrosis. Aminoglycosides preferentially affect the proximal tubular cells. Aminoglycoside antibiotics, such as gentamicin can produce nephrotoxicity, due. Effect of cyclooxygenase inhibitors on gentamicininduced nephrotoxicity in rats. Effect of dimethyl sulfoxide on gentamicininduced nephrotoxicity in rats. Effect of cimetidine on gentamicinlosartan inducednephrotoxicity in. Combining an aminoglycoside with a known nephrotoxin can enhance. Finally, gentamicin nephrotoxicity is potentiated by magnesium depletion 27.
Integrated transcriptomic and proteomic evaluation of. The effects of sex hormones on gm induced nephrotoxicity in gonadectomized rats were investigated. A significant decrease in 14c inulin p rats receiving high doses of antibiotics. Flavocoxid attenuates gentamicininduced nephrotoxicity in.
In old rats, diabetes had significantly less protective effect on the gentamicininduced nephrotoxic signs than in the young rats. Gentamicin nephrotoxicity in diabetic old rats induced mortality in about a third of the animals used, whereas no mortality was. 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 gentamicinadministered rats. Gentamicin nephrotoxicity occurs in 1020% of therapeutic regimes. Gentamicin gm is one of the aminoglycoside drugs which is commonly used for treatment of negative gram bacterial infections 1, 2. Study was conducted in the department of histopathology with the collaboration of the department of. Gentamicininduced ototoxicity and nephrotoxicity vary. Pdf inhibitory effect of olive leaf extract on gentamicininduced. Materials experimental animals male wistar rats weighing 150250g were used and were procured from national center for lab animal sciences, national institution of nutrition, hyderabad, india. Nephrotoxicity is the main limitation to its therapeutic efficacy.
Protective effect of transresveratrol on gentamicin. In the current study a dose of 80 mgkg gentamicin was given daily to male rats for one week. This study demonstrates an improvement in renal function in response to the administration of tr. Conclusions this case illustrates nonoliguric acute renal failure possibly induced by gentamicn.
The present study was designed to determine whether flavocoxid has a protective effect against gentamicininduced nephrotoxicity in rats. The activities of lactate dehydrogenase and alkaline phosphatase were higher in rats treated with gentamicin than in control rats and were reduced by the treatment with tr. It is not recommended that these drugs be used in pregnant rats. Some loop diuretics seem to increase gentamicin nephrotoxicity. Increased nephrotoxicity of gentamicin in pyelonephritic rats. Aminoglycosideinduced nephrotoxicity in children springerlink. Due to high relative blood flow the kidney is prone to drug induced damage. Gentamicin nephrotoxicity in diabetic old rats induced mortality in about a third of the animals used, whereas no mortality was seen in young diabetic rats treated with gentamicin. Assessment of gentamicininduced nephrotoxicity in rats. So, it was hypothesized that there may be involvement of oxidative stress in gentamicin nephrotoxicity. Protective effect of apocynin against gentamicininduced nephrotoxicity in rats show all authors. Newborn puppies were paired n 21 pairs at birth, given gentamicin 5 mgkgday for 7 days and then 7. Gentamicin has been shown to lead to release of iron from renal cortical mitochondria and to enhance generation of hvdroxyl radical.
We have examined the role of reactive oxygen metabolites rom in gentamicin nephrotoxicity and in glycerolinduced acute renal failure, a model for myoglobinuric acute renal failure. Can gentamicin nephrotoxicity in rats be modified by. Nephrotoxicity was induced in rats by intraperitoneal injection i. Gentamicin has no known severe interactions with other drugs. Atpase activity in brush border membrane of rat proximal tubuli was selectively damaged in gentamicin nephrotoxicity. The effects of two nonsteroidal antiinflammatory drugs, ibuprofen 20 mg day. Thus, gentamicin is frequently used as a first or second choice drug in the clinic 4. The study findings indicate robust difference of the time course in rats of both treatment groups of gentamicininduced ototoxicity and nephrotoxicity, supporting the hypothesis these organ toxicities are independent of one another, and further suggest the observed treatmenttime differences in gentamicin adverse effects may be more dependent.
Integrative overview on the mechanisms underlying the. Request pdf effect of cimetidine on gentamicinlosartan inducednephrotoxicity in rats. Concomitant gentamicininduced nephrotoxicity and bilateral ototoxicity aa akinbodewa 1, o okunola 2 1 department of medicine, kidney care centre, university of medical sciences, ondo, ondo state, nigeria 2 department of renal unit, obafemi awolowo university teaching hospital, ile ife, osun state, nigeria. Given its continued use in drug therapy, considerable research has been aimed at developing approaches to reduce aminoglycoside toxicity in patients. In this study, we aimed to investigate the possible protective effect of resveratrol on gentamicin induced nephrotoxicity. The pathogenesis of gentamicin nephrotoxicity is unclear. Protective effect of apocynin against gentamicininduced. Gentamicin administration caused a severe nephrotoxicity as evidenced by an.
In addition, based on the experimental and clinical studies, the possible therapeutic approach to prevent gentamicininduced nephrotoxicity has been discussed. When a dose of 40 mgkg per day was administered intramuscularly to fischer rats for 14 days, ribostamycin caused little change of parameters in urine volume, urine osmolality, urine protein, maltase and beta 2microglobulin. Gentamicin gm induced nephrotoxicity may be sex hormones related. Identification of genes involved in gentamicin induced. Pinocembrin attenuates gentamicininduced nephrotoxicity. Each rat was given gentamicin intraperitoneally in a dosage that induces morphological and functional modifications in the kidneys 20 mgkgday for 7 days. The possibility of concurrently administered drugs causing this adverse reaction was ruled out. 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. Protective effect of fosfomycin on gentamicininduced lipid peroxidation of rat. Gentamicin is a widely used antibiotic against serious and lifethreatening infections. The rats were randomly assigned to either the gentamicin injection without garlic supplementation group group i, n 8, genta. Abstract the nephrotoxicity of ribostamycin and gentamicin was compared by urinalysis using 18 parameters.
The role of sex hormones in gonadectomized male and female rats fatemeheshraghijazi, 1 ardeshirtalebi, 1,2 fatemehsadatmirsaeedi, 1 sarinaahmadian, 1. Bun with recovery in creatinine clearance and holding atpase activity up to 50% on comparison with the control and. Protective effect of crocin on gentamicininduced nephrotoxicity in rats. Gentamicin gm is a widely used antibiotic against serious and lifethreatening infections, but its usefulness is limited by the development of nephrotoxicity.
This study aimed to investigate the possible protective effect of apocynin apo on nephrotoxicity induced by gnt in rats. 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. Comparison of gentamicin nephrotoxicity between rats and. Histopathologic alterations in cortical area of rat kidneys following gentamicin. A similar kind of approach functional analysis was applied for integrating transcriptomic and proteomic evaluation of gentamicin nephrotoxicity in rats by com et al. For this purpose, we quantitatively evaluated gentamicininduced renal structural and functional. Experiments were carried out in male wistar rats weighing 200250g.
Influence of iron, deferoxamine and ascorbic acid on gentamicininduced nephrotoxicity in rats. Protective effect of allicin against gentamicininduced nephrotoxicity. In light microscopic analysis, 80 mgkg gentamicin produced necrosis in the greater part of rat kidney proximal tubuli with no pathological findings in mouse kidney. If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Gentamicin, as with other aminoglycosides, should be used with caution in existing renal conditions or neuromuscular disease. Despite significant research in this field, the molecular mechanism associated with gentamicin nephrotoxicity. The patient was not rechallenged with gentamicin due to the high possibility of this diagnosis. Aminoglycoside type antibiotic gentamicin is one of the leading cause of drug induced nephrotoxicity. Gentamicininduced apoptosis in renal cell lines and embryonic rat. Finally, there is evidence for oxidative stress in gentamicininduced nephrotoxicity. The aim of the current study was to investigate the mechanisms of renoprotection elicited by pinocembrin in gentamicininduced nephrotoxicity. Effect of cimetidine on gentamicinlosartan induced nephrotoxicity in rats.
Gentamicininduced nephrotoxicity in rats ameliorated and. In conclusion, the intratubular ph of the proximal tubule is a factor which influences the cortical uptake of gentamicin, probably by means of changing the cationic nature of the molecule and, therefore, reduced. Antibiotics are a widespread class of drugs and the principal cause of drugassociated nephropathy. Rapamycin protects against gentamicininduced acute kidney.
184 633 797 56 1516 684 573 1120 833 385 916 1273 105 539 137 1255 838 1319 593 720 1108 960 571 51 230 1072 196 586 283 149