The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin induced nephrotoxicity in. Gentamicin injection is a sterile, nonpyrogenic, aqueous solution for parenteral administration and is available both with and without preservatives. Gentamicin induced nephrotoxicity ranges between 8% and 26%, while by audiometry about 25% of patients on aminoglycoside therapy develop ototoxicity. It is not effective for gonorrhea or chlamydia infections. Amginduced glomerular toxicity shows the following breakdown. Each regimen must be followed by at least trough level drawn on third or fourth dose, 30 min before dosing unless renal toxicity suspected.
The collective number of patients in the reports was 165. Aminoglycosideinduced nephrotoxicity article pdf available in journal of pharmacy practice 276 september 2014 with 1,253 reads how we measure reads. However, its usefulness is limited by its nephrotoxicity. Gentamicininduced acute renal failure model creative. Patients at highest risk of drug induced nephrotoxicity are those with one or more of the following. Inhibitory effect of olive leaf extract on gentamicininduced nephrotoxicity in rats majid tavafi, 1 hasan ahmadvand, 2 pooran toolabi 3 introduction. In addition, based on the experimental and clinical studies, the. 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. Effect of dimethyl sulfoxide on gentamicin induced nephrotoxicity in rats. A prospective comparative study of gentamicin and amikacininduced nephrotoxicity in patients with normal baseline renal function waleed 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. Gentamicininduced acute renal failure model creative biolabs. When possible, the drug may be administered in a single daily total dose, which leads to lower renal proximal tubular cell accumulation. Patients at highest risk of druginduced nephrotoxicity are those with one or more of the following. Calcium dobesilate is an antioxidant drug and this study is aimed to investigate the effects of calcium dobesilate on gentamicin induced nephrotoxicity. Diagnosis and treatment aminoglycoside nephrotoxicity typically is associated with nonoliguric acute renal failure, that is, azotemia in the presence. Sep 07, 2014 aminoglycosideinduced nephrotoxicity article pdf available in journal of pharmacy practice 276 september 2014 with 1,253 reads how we measure reads. Effect of treatment of mice with gentamicin gen and sitagliptin sita on. Importance of apoptosis in aminoglycosideinduced nephrotoxicity 36. The medical issues surrounding gentamicin administration and resulting ototoxicity and nephrotoxicity can be divided into 6 broad categories as set forth below.
Gentamicin was given daily until the plasma creatinine level of each sheep increased to a minimum of 2. 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. Complete protection from gentamicininduced acute renal failure in the diabetes mellitus rat. Risk factors and comparisons of clinical nephrotoxicity of aminoglycosides. 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. Inhibitory effect of olive leaf extract on gentamicininduced. Nephrotoxicity due to a aminoglycosides b cyclophosphamide c cisplatin d radiocontrast e analgesic f amphotericin g crystal. Gentamicin sulfate is a powerful antibiotic delivered intravenously to patients in hospitals, nursing homes, and home healthcare settings to combat severe infections. Animals were injected during 4 or 10 days with saline nacl. This work was conducted to evaluate the possible renoprotective effect of eryngium caucasicum against gentamicin induced renotoxicity. Adverse effects 1, 2 hypomagnesaemia, hypocalcaemia, hypokalaemia.
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. Ginkgo biloba extract protected rats from gentamicininduced nephrotoxicity. Seasonal effects on the daily variations of gentamicin. Amg induced glomerular toxicity shows the following breakdown. Plajer sm, chin pk, vellabrincat jw, buffery pj, begg ej. A congener of gentamicin has also been isolated that retains clinical efficacy, but does not cause nephrotoxicity.
Structural latency of lysosomal nacetyl3glucosaminidasefollowing gentamicin treatment mean of four independent experiments sem. Druginduced nephrotoxicity tends to be more common among certain patients and in specific clinical situations. Gentamicin is inactivated by solutions containing penicillins. Protective effect of crocin on gentamicininduced nephrotoxicity in rats. Aminoglycoside nephrotoxicity kidney international. Recommendations issued for preventing druginduced nephrotoxicity.
Links are provided to pages with a more indepth analysis of each of these categories. Patients ranged in age from 3 days to 19 years old. 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. Pdf acute and chronic nephrotoxicity frequently limits the therapeutic benefits of immunosuppressive therapy for transplant and autoimmune. Aminoglycosideinduced nephrotoxicity is characterised by selective. The protection against gentamicin nephrotoxicity in the streptozotocin induced diabetic rat is not related to gender. Aminoglycosides have long been one of the commonest causes of druginduced nephrotoxicity. Dailymed gentamicin gentamicin sulfate injection, solution. 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. Nov 21, 2016 gentamicin injection is a sterile, nonpyrogenic aqueous solution for parenteral administration.
Sildenafil ameliorates gentamicininduced nephrotoxicity. There are also reports of chip models combining liver and kidney cells. Mar 31, 2015 evaluation seminar on molecular mechanisms of drug induced nephrotoxicity. Olive leaf extract ole has been demonstrated to have antioxidant and antiinflammatory. Gentamicin is an effective treatment, but only when properly administered and monitored by a medical professional. Drug induced nephrotoxicity tends to be more common among certain patients and in specific clinical situations. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicininduced nephrotoxicity in rats. Gentamicin sulfate, a watersoluble antibiotic of the aminoglycoside group, is derived from micromonospora purpurea, an actinomycete it has the following structural formula. 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. Aminoglycosideinduced nephrotoxicity in children springerlink.
Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious gramnegative infections. Gentamicininduced in animals by intravenous injection of gentamicin sulphate gentacin 5%, nasr,fariman, iran at a dose rate of 80 mgkg per day. Gentamicin is a broadspectrum aminoglycoside antibiotic produced by fermentation of micromonospora purpurea or m. Finally, gentamicin nephrotoxicity is potentiated by magnesium depletion 27. Nephrotoxicity with combination vancomycinaminoglycoside. Inhibitory effect of olive leaf extract on gentamicin. Previously we studied the hydrogen peroxide scavenging activity of eryngium caucasicum. Gentamicin induced ototoxicity gentamicin poisoning. Due to high relative blood flow the kidney is prone to drug induced damage. Gentamicin sulphate nephrotoxicity seems to be attributed to the generation of reactive oxygen species. Ginkgo biloba extract ameliorates gentamicininduced. Gentamicin induced nephrotoxicity 585 gentamicin for 8 days, mgkg fig. Patients with impaired renal function, advanced age, dehydration, and those who receive high doses or prolonged therapy are at an increased risk of toxicity.
In addition, patients with compromised renal function eliminate gentamicin more slowly than patients with normal renal function. 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. Effect of dimethyl sulfoxide on gentamicininduced nephrotoxicity in rats. The cessation of the treatment allows a recovery to control values within approximately 8 days. However, many do not know that, contrary to textbooks and antibiotic guidelines, gentamicin ototoxicity causes impairment of vestibular. Pdf gentamicin sulphate nephrotoxicity seems to be attributed to the generation of reactive oxygen species. 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. Pdf amelioration of gentamicin induced dyslipidemia in. Nephrotoxicity due to a aminoglycosides b cyclophosphamide c cisplatin d radiocontrast e analgesic f. 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. Pdf attenuation of gentamicininduced nephrotoxicity in. 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.
Injection route solution therapy has been associated with potential neurotoxicity, ototoxicity, and nephrotoxicity. Rats were either treated with chrysin 10, 20 and 40 mg kgg 1, p. Aminoglycosideinduced nephrotoxicity is characterised by selective targeting of the. Gentamicin sulfate equivalent to 40 mg gentamicin, methylparaben 1. Identification of genes involved in gentamicin induced. Pdf inhibitory effect of olive leaf extract on gentamicininduced. The drug induced nephrotoxicity is more common in patients receiving certain medication and undergoing certain specific clinical conditions. It can be given intravenously, by injection into a muscle. Gentamicin injection is a sterile, nonpyrogenic aqueous solution for parenteral administration. Sildenafil, a selective phosphodiesterase5 inhibitor, was reported to prevent or decrease tissue injury. Pdf gentamicininduced nephrotoxicity and nephroneogenesis in. Gentamicin serum levels should be followed to minimize nephrotoxicity. Until these interventions become adopted in clinical practice, however, clinicians must utilize established strategies to reduce the incidence of. May draw peak level 30 min after 30min infusion has been completed or 1 hr after im injection.
Inhibitory effect of olive leaf extract on gentamicin induced nephrotoxicity in rats majid tavafi, 1 hasan ahmadvand, 2 pooran toolabi 3 introduction. Gentamicin, tobramycin, and netilmicin appear to have similar nephrotoxic effects. Although the exact mechanism of gentamicininduced nephrotoxicity is not well. 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. Esterhai jl, bednar j, kimmelman cp gentamicininduced ototoxicity complicating treatment of chronic osteomyelitis. Studying the possible usefulness of combining this drug with commonly used. Main approaches toward reduction of aminoglycoside nephrotoxicity a. Nephrotoxicity was induced by intraperitoneal injection of gentamicin 100 mgkg for 8 days. The effect of the dipeptidyl peptidase4 inhibitor sitagliptin on.
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. Aminoglycosides have long been one of the commonest causes of drug induced nephrotoxicity. A number of crude herbal extracts have been reported to ameliorate gentamicininduced nephrotoxicity. The risk of aminoglycosideinduced nephrotoxicity and ototoxicity, although controversial in newborns, must still be considered a potential hazard related to drug accumulation.
Gentamicin nephrotoxicity and agents that modify it. Doubleblind comparison of the nephrotoxicity and auditory. Esterhai jl, bednar j, kimmelman cp gentamicin induced ototoxicity complicating treatment of chronic osteomyelitis. Monitor renal and auditory function during therapy and discontinue therapy or adjust dose if.
Finally, there is evidence for oxidative stress in gentamicininduced nephrotoxicity. Effect of superoxide dismutase treatment on gentamicin nephrotoxicity in rats. Sildenafil ameliorates gentamicininduced nephrotoxicity in. Morin jp, viotte g, vandewalle a, van hoof f, tulkens p, fillastre jp 1980 gentamicin induced nephrotoxicity a cell biology approach. Influence of iron, deferoxamine and ascorbic acid on gentamicin induced nephrotoxicity in rats. Gentamicin, sold under brand name garamycin among others, is an antibiotic used to treat several types of bacterial infections. Presently, the study investigated the effect of piperine and. Concurrent use of other potentially neurotoxic or nephrotoxic agents, or potent diuretics should be avoided. Jun 04, 2012 the gentamicin dose ranged from 160 to 320 mgday, equivalent to 1. The effect of fleroxacin on gentamicin induced nephrotoxicity was evaluated with female spraguedawley rats.
Gouvea w, vaamonde cm, owens b, alpert h, pardo v, vaamonde ca. Gentamicin is an antibiotic complex consisting of four major c1, c1a, c2, and c2a and several minor components. Aminoglycosideinduced renal phospholipidosis and nephrotoxicity. Aminoglycoside type antibiotic gentamicin is one of the leading cause of drug induced nephrotoxicity.
The protection against gentamicin nephrotoxicity in the streptozotocininduced diabetic rat. Nephrotoxicity was induced in male spraguedawley rats 220250 g by intraperitoneal administration of gentamicin 120 mg kgg 1 for 7 consecutive days. Complete protection from gentamicin induced acute renal failure in the diabetes mellitus rat. Intracellular mechanisms of apoptosis induced by aminoglycoside antibiotics sophie denamur. Complete protection from gentamicininduced acute renal failure in. Amelioration of gentamicin induced dyslipidemia in guinea pigs by curcumin and rosemary article pdf available may 2017 with 141 reads how we measure reads. Gentamicin, at doses of 50 or 100 mgkg body wt administered daily to healthy male mf1 mice by i.
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. G entamicin is an important bactericidal antibiotic with two serious potential adverse effects. Risk of aki with gentamicin as surgical prophylaxis. Gentamicininduced nephrotoxicity kidney international. In recent years gentamicin nephrotoxicity is significantly reduced by shifting to once daily dosage as well as by eliminating known risk factors. 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. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis among others. A prospective comparative study of gentamicin and amikacin. G mycetin, garamycin gentamicin dosing, indications. Nephrotoxic effects of aminoglycosides on the developing kidney. Aminoglycosideinduced nephrotoxicity in children ncbi. Sweileh clinical pharmacology, annajah national university, nablus, palestine introduction aminoglycosides are commonly used in everyday clinical practice for the treatment of gramnegative infections 1.
Influence of iron, deferoxamine and ascorbic acid on gentamicininduced nephrotoxicity in rats. Calcium dobesilate for prevention of gentamicininduced nephrotoxicity in rats mostafa jafarey,1 saeed changizi ashtiyani,2 houshang najafi3 introduction. In the current study a dose of 80 mgkg gentamicin was given daily to male rats for one week. Extracts at the doses 200 and 400 mgkgday for 10 consecutive days, by intraperitoneal route i. Calcium dobesilate for prevention of gentamicininduced. Original article from the new england journal of medicine doubleblind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin logo32 logo40. Pdf aminoglycosides have long been one of the commonest causes of druginduced. Serum concentrations of aminoglycosides should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels. Apr 18, 2019 aminoglycoside induced ototoxicity is usually irreversible. The total gentamicin dose ranged from 160 to 16 520 mg, equivalent to 2 318 mgkg mean, 3639 mg or 52 mgkg. For this reason, gentamicin and penicillins should not be combined in iv injectionsinfusions. This agent irreversibly binds to the bacterial 30s ribosomal subunit. Concomitant gentamicininduced nephrotoxicity and bilateral.
Clinicians are well aware that rising serum creatinine levels in patients treated with gentamicin could indicate nephrotoxicity. Aminoglycosideinduced nephrotoxicity indiana university. Aminoglycoside induced renal phospholipidosis and nephrotoxicity. Until these interventions become adopted in clinical practice, however, clinicians must utilize established strategies to reduce the incidence of aminoglycoside induced nephrotoxicity. Nephroprotective effect of punica granatum in gentamicin. 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.
Calcium dobesilate for prevention of gentamicin induced nephrotoxicity in rats mostafa jafarey,1 saeed changizi ashtiyani,2 houshang najafi3 introduction. A number of crude herbal extracts have been reported to ameliorate gentamicin induced nephrotoxicity. Monitor nephrotoxicity, neurotoxicity, and ototoxicity. Study of protective effects of stem bark extracts of ficus racemosa in drug induced.
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