Gentamicin, at doses of 50 or 100 mgkg body wt administered daily to healthy male mf1 mice by i. Studying the possible usefulness of combining this drug with commonly used. Pdf amelioration of gentamicin induced dyslipidemia in. The effect of aepf 100mgkg given orally either with gentamicin or after 8 days of gentamicin administration was assessed by biochemical and histopathological changes of kidneys. However, its usefulness is limited by its nephrotoxicity. Previously we studied the hydrogen peroxide scavenging activity of eryngium caucasicum. Serum concentrations of aminoglycosides should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels. Intracellular mechanisms of apoptosis induced by aminoglycoside antibiotics sophie denamur. Gentamicin nephrotoxicity and agents that modify it. This work was conducted to evaluate the possible renoprotective effect of eryngium caucasicum against gentamicin induced renotoxicity. Patients with impaired renal function should be monitored closely while on gentamicin therapy because nephrotoxicity caused by gentamicin may be difficult to distinguish from the symptoms of underlying renal disease. A congener of gentamicin has also been isolated that retains clinical efficacy, but does not cause nephrotoxicity. Gentamicininduced acute renal failure model creative biolabs.
Adverse effects 1, 2 hypomagnesaemia, hypocalcaemia, hypokalaemia. Gentamicin, tobramycin, and netilmicin appear to have similar nephrotoxic effects. Concurrent use of other potentially neurotoxic or nephrotoxic agents, or potent diuretics should be avoided. Aminoglycoside nephrotoxicity kidney international. When possible, the drug may be administered in a single daily total dose, which leads to lower renal proximal tubular cell accumulation. Pdf inhibitory effect of olive leaf extract on gentamicininduced.
Calcium dobesilate is an antioxidant drug and this study is aimed to investigate the effects of calcium dobesilate on gentamicininduced nephrotoxicity. Original article from the new england journal of medicine doubleblind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin logo32 logo40. It can be given intravenously, by injection into a muscle. Plajer sm, chin pk, vellabrincat jw, buffery pj, begg ej. Gentamicin induced nephrotoxicity ranges between 8% and 26%, while by audiometry about 25% of patients on aminoglycoside therapy develop ototoxicity. Pdf gentamicin sulphate nephrotoxicity seems to be attributed to the generation of reactive oxygen species. G entamicin is an important bactericidal antibiotic with two serious potential adverse effects.
Pdf aminoglycosides have long been one of the commonest causes of druginduced. Rats were either treated with chrysin 10, 20 and 40 mg kgg 1, p. Gentamicin sulfate, a watersoluble antibiotic of the aminoglycoside group, is derived from micromonospora purpurea, an actinomycete it has the following structural formula. Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious gramnegative infections. The cessation of the treatment allows a recovery to control values within approximately 8 days. Gentamicin, sold under brand name garamycin among others, is an antibiotic used to treat several types of bacterial infections. Nephrotoxicity was induced in male spraguedawley rats 220250 g by intraperitoneal administration of gentamicin 120 mg kgg 1 for 7 consecutive days. Extracts at the doses 200 and 400 mgkgday for 10 consecutive days, by intraperitoneal route i.
May draw peak level 30 min after 30min infusion has been completed or 1 hr after im injection. The drug induced nephrotoxicity is more common in patients receiving certain medication and undergoing certain specific clinical conditions. Dailymed gentamicin gentamicin sulfate injection, solution. Aminoglycosideinduced nephrotoxicity is characterised by selective. Complete protection from gentamicininduced acute renal failure in the diabetes mellitus rat. Inhibitory effect of olive leaf extract on gentamicin. Sweileh clinical pharmacology, annajah national university, nablus, palestine introduction aminoglycosides are commonly used in everyday clinical practice for the treatment of gramnegative infections 1. Gentamicininduced nephrotoxicity kidney international. Aminoglycosides have long been one of the commonest causes of drug induced nephrotoxicity. The medical issues surrounding gentamicin administration and resulting ototoxicity and nephrotoxicity can be divided into 6 broad categories as set forth below.
Ginkgo biloba extract ameliorates gentamicininduced. 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. Nephrotoxicity was induced by intraperitoneal injection of gentamicin 100 mgkg for 8 days. Calcium dobesilate is an antioxidant drug and this study is aimed to investigate the effects of calcium dobesilate on gentamicin induced nephrotoxicity. Gentamicin is an antibiotic complex consisting of four major c1, c1a, c2, and c2a and several minor components.
This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis among others. One case report, two letters to editors, one retrospective study, and two prospective studies evaluated the nephrotoxicity of combination aminoglycoside and vancomycin therapy in pediatric patients. Gentamicin induced ototoxicity gentamicin poisoning. Sildenafil ameliorates gentamicininduced nephrotoxicity. Olive leaf extract ole has been demonstrated to have antioxidant and antiinflammatory. Druginduced nephrotoxicity tends to be more common among certain patients and in specific clinical situations. Influence of iron, deferoxamine and ascorbic acid on gentamicininduced nephrotoxicity in rats.
Pdf attenuation of gentamicininduced nephrotoxicity in. Gentamicininduced in animals by intravenous injection of gentamicin sulphate gentacin 5%, nasr,fariman, iran at a dose rate of 80 mgkg per day. Aminoglycosideinduced renal phospholipidosis and nephrotoxicity. Patients at highest risk of drug induced nephrotoxicity are those with one or more of the following. Seasonal effects on the daily variations of gentamicin. Amelioration of gentamicin induced dyslipidemia in guinea pigs by curcumin and rosemary article pdf available may 2017 with 141 reads how we measure reads. Complete protection from gentamicininduced acute renal failure in. Aminoglycoside type antibiotic gentamicin is one of the leading cause of drug induced nephrotoxicity. Doubleblind comparison of the nephrotoxicity and auditory. Nov 21, 2016 gentamicin injection is a sterile, nonpyrogenic aqueous solution for parenteral administration. Gentamicin is an aminoglycoside antibiotic used in the treatment of severe infections often in combination with other antibiotics including endocarditis also in combination with other antibiotics. In addition, based on the experimental and clinical studies, the.
Gentamicin induced nephrotoxicity 585 gentamicin for 8 days, mgkg fig. Main approaches toward reduction of aminoglycoside nephrotoxicity a. Gentamicin sulfate is a powerful antibiotic delivered intravenously to patients in hospitals, nursing homes, and home healthcare settings to combat severe infections. Gentamicin is an effective treatment, but only when properly administered and monitored by a medical professional. Protective effect of crocin on gentamicininduced nephrotoxicity in rats. Ginkgo biloba extract protected rats from gentamicininduced nephrotoxicity. Influence of iron, deferoxamine and ascorbic acid on gentamicin induced nephrotoxicity in rats. Until these interventions become adopted in clinical practice, however, clinicians must utilize established strategies to reduce the incidence of aminoglycoside induced nephrotoxicity.
Gentamicin induced acute renal failure model a variety of exogenous mainly drugs or endogenous toxins cause acute kidney injury aki in humans and in experimental animals. There are also reports of chip models combining liver and kidney cells. Effect of treatment of mice with gentamicin gen and sitagliptin sita on. In addition, patients with compromised renal function eliminate gentamicin more slowly than patients with normal renal function. Gentamicin sulfate equivalent to 40 mg gentamicin, methylparaben 1. Pdf the renal response to 2 doses of gentamicin low dose of 5 mg kg1 of body weight and high dose of 25 mg kg1 of body weight was examined in.
Pdf gentamicininduced nephrotoxicity and nephroneogenesis in. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicininduced nephrotoxicity in rats. Esterhai jl, bednar j, kimmelman cp gentamicin induced ototoxicity complicating treatment of chronic osteomyelitis. Calcium dobesilate for prevention of gentamicininduced. Amg induced glomerular toxicity shows the following breakdown. The effect of the dipeptidyl peptidase4 inhibitor sitagliptin on. The total gentamicin dose ranged from 160 to 16 520 mg, equivalent to 2 318 mgkg mean, 3639 mg or 52 mgkg. Aminoglycosideinduced nephrotoxicity in children ncbi. Finally, there is evidence for oxidative stress in gentamicininduced nephrotoxicity. A prospective comparative study of gentamicin and amikacininduced nephrotoxicity in patients with normal baseline renal function waleed m. Animals were injected during 4 or 10 days with saline nacl.
Gentamicin serum levels should be followed to minimize nephrotoxicity. Although the rates of aki we observed are similar to other reported rates of gentamicin nephrotoxicity, 1,2,5,1012 it is clear that these rates are higher than in some studies, which in part may be due to differing definitions of nephrotoxicity. Thus, this property of drugstoxin is utilized by investigators to induce disease models for clinical research of potential drugs as well as to study the pathogenesis of. Nephrotoxicity with combination vancomycinaminoglycoside. Gentamicin is inactivated by solutions containing penicillins. Nephrotoxicity due to a aminoglycosides b cyclophosphamide c cisplatin d radiocontrast e analgesic f amphotericin g crystal. Gentamicininduced acute renal failure model a variety of exogenous mainly drugs or endogenous toxins cause acute kidney injury aki in humans and in experimental animals. For this reason, gentamicin and penicillins should not be combined in iv injectionsinfusions. A prospective comparative study of gentamicin and amikacin. Aminoglycosideinduced nephrotoxicity in children springerlink.
Monitor nephrotoxicity, neurotoxicity, and ototoxicity. Patients ranged in age from 3 days to 19 years old. A number of crude herbal extracts have been reported to ameliorate gentamicininduced nephrotoxicity. Patients with impaired renal function, advanced age, dehydration, and those who receive high doses or prolonged therapy are at an increased risk of toxicity. Risk factors and comparisons of clinical nephrotoxicity of aminoglycosides. Sep 07, 2014 aminoglycosideinduced nephrotoxicity article pdf available in journal of pharmacy practice 276 september 2014 with 1,253 reads how we measure reads. In recent years gentamicin nephrotoxicity is significantly reduced by shifting to once daily dosage as well as by eliminating known risk factors. Study of protective effects of stem bark extracts of ficus racemosa in drug induced. Although the exact mechanism of gentamicininduced nephrotoxicity is not well.
Research article gentamicin induced hepatorenal toxicity. Aminoglycosides have long been one of the commonest causes of druginduced nephrotoxicity. Complete protection from gentamicin induced acute renal failure in the diabetes mellitus rat. Amginduced glomerular toxicity shows the following breakdown. Gentamicininduced acute renal failure model creative.
Effect of chrysin on gentamicininduced nephrotoxicity in. Recommendations issued for preventing druginduced nephrotoxicity. The effect of fleroxacin on gentamicin induced nephrotoxicity was evaluated with female spraguedawley rats. 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. It is not effective for gonorrhea or chlamydia infections. Inhibitory effect of olive leaf extract on gentamicininduced. Esterhai jl, bednar j, kimmelman cp gentamicininduced ototoxicity complicating treatment of chronic osteomyelitis. The risk of aminoglycosideinduced nephrotoxicity and ototoxicity, although controversial in newborns, must still be considered a potential hazard related to drug accumulation. Aminoglycosideinduced nephrotoxicity is characterised by selective targeting of the. Therefore, successful prevention requires knowledge of pathogenic mechanisms of renal injury, patientrelated risk factors, drugrelated risk factors, and preemptive measures, coupled with early identification and intervention.
Concomitant gentamicininduced nephrotoxicity and bilateral. Aminoglycosideinduced nephrotoxicity article pdf available in journal of pharmacy practice 276 september 2014 with 1,253 reads how we measure reads. Sildenafil ameliorates gentamicininduced nephrotoxicity in. Structural latency of lysosomal nacetyl3glucosaminidasefollowing gentamicin treatment mean of four independent experiments sem. 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. Diagnosis and treatment aminoglycoside nephrotoxicity typically is associated with nonoliguric acute renal failure, that is, azotemia in the presence. This agent irreversibly binds to the bacterial 30s ribosomal subunit. Morin jp, viotte g, vandewalle a, van hoof f, tulkens p, fillastre jp 1980 gentamicin induced nephrotoxicity a cell biology approach. Gouvea w, vaamonde cm, owens b, alpert h, pardo v, vaamonde ca. Gentamicin sulphate nephrotoxicity seems to be attributed to the generation of reactive oxygen species. 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 due to a aminoglycosides b cyclophosphamide c cisplatin d radiocontrast e analgesic f. Inhibitory effect of olive leaf extract on gentamicininduced nephrotoxicity in rats majid tavafi, 1 hasan ahmadvand, 2 pooran toolabi 3 introduction.
The protection against gentamicin nephrotoxicity in the streptozotocin induced diabetic rat is not related to gender. Finally, gentamicin nephrotoxicity is potentiated by magnesium depletion 27. The collective number of patients in the reports was 165. Patients at highest risk of druginduced nephrotoxicity are those with one or more of the following. Injection route solution therapy has been associated with potential neurotoxicity, ototoxicity, and nephrotoxicity. A number of crude herbal extracts have been reported to ameliorate gentamicin induced nephrotoxicity. Aminoglycosideinduced nephrotoxicity indiana university. Effect of superoxide dismutase treatment on gentamicin nephrotoxicity in rats. Mar 31, 2015 evaluation seminar on molecular mechanisms of drug induced nephrotoxicity.
Each regimen must be followed by at least trough level drawn on third or fourth dose, 30 min before dosing unless renal toxicity suspected. Calcium dobesilate for prevention of gentamicininduced nephrotoxicity in rats mostafa jafarey,1 saeed changizi ashtiyani,2 houshang najafi3 introduction. Links are provided to pages with a more indepth analysis of each of these categories. Nephrotoxic effects of aminoglycosides on the developing kidney. Gentamicin was given daily until the plasma creatinine level of each sheep increased to a minimum of 2. Presently, the study investigated the effect of piperine and. Nephroprotective effect of punica granatum in gentamicin. In the current study a dose of 80 mgkg gentamicin was given daily to male rats for one week. Pdf acute and chronic nephrotoxicity frequently limits the therapeutic benefits of immunosuppressive therapy for transplant and autoimmune. However, many do not know that, contrary to textbooks and antibiotic guidelines, gentamicin ototoxicity causes impairment of vestibular. Effect of dimethyl sulfoxide on gentamicin induced nephrotoxicity in rats. Nephrotoxicity induced by gentamicin is a complex phenomenon characterized by an increase in serum creatinine cr, blood urea nitrogen bun concentration and severe proximal renal tubular necrosis, followed by deterioration and renal failure. Calcium dobesilate for prevention of gentamicin induced nephrotoxicity in rats mostafa jafarey,1 saeed changizi ashtiyani,2 houshang najafi3 introduction.
Jun 04, 2012 the gentamicin dose ranged from 160 to 320 mgday, equivalent to 1. Until these interventions become adopted in clinical practice, however, clinicians must utilize established strategies to reduce the incidence of. Monitor renal and auditory function during therapy and discontinue therapy or adjust dose if. Gentamicin is a broadspectrum aminoglycoside antibiotic produced by fermentation of micromonospora purpurea or m. The mean total dose in the 43 patients who developed nephrotoxicity was 4363 mg, in contrast to 3240 mg in the 60 who did not. Gentamicin injection is a sterile, nonpyrogenic, aqueous solution for parenteral administration and is available both with and without preservatives. Drug induced nephrotoxicity tends to be more common among certain patients and in specific clinical situations. Effect of dimethyl sulfoxide on gentamicininduced nephrotoxicity in rats.
Importance of apoptosis in aminoglycosideinduced nephrotoxicity 36. The protection against gentamicin nephrotoxicity in the streptozotocininduced diabetic rat. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin induced nephrotoxicity in. Jan 01, 2002 the risk of aminoglycosideinduced nephrotoxicity and ototoxicity, although controversial in newborns, must still be considered a potential hazard related to drug accumulation. Clinicians are well aware that rising serum creatinine levels in patients treated with gentamicin could indicate nephrotoxicity. Due to high relative blood flow the kidney is prone to drug induced damage. Gentamicin injection is a sterile, nonpyrogenic aqueous solution for parenteral administration. Aminoglycoside induced renal phospholipidosis and nephrotoxicity. Inhibitory effect of olive leaf extract on gentamicin induced nephrotoxicity in rats majid tavafi, 1 hasan ahmadvand, 2 pooran toolabi 3 introduction. G mycetin, garamycin gentamicin dosing, indications. Sildenafil, a selective phosphodiesterase5 inhibitor, was reported to prevent or decrease tissue injury. Risk of aki with gentamicin as surgical prophylaxis.