Green coffee bean extract attenuates gentamicin induced acute nephrotoxicity in rats / El extracto de grano de café verde atenúa la nefrotoxicidad aguda inducida por gentamicina en ratas

Gentamicin induced acute nephrotoxicity (GIAN) is considered as one of the important causes of acute renal failure. In recent years' great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of GIAN. Hence, the current study was designed to investigate the effect of green coffee bean extract (GCBE) on GIAN in rats. Results of the present study showed that rat groups that received oral GCBE for 7 days after induction of GIAN(by a daily intraperitoneal injection of gentamicin for 7days), reported a significant improvement in renal functions tests when compared to the GIAN model groups. Moreover, there was significant amelioration in renal oxidative stress markers (renal malondialdehyde, renal superoxide dismutase) and renal histopathological changes in the GCBE-treated groups when compared to GIAN model group. These results indicate that GCBE has a potential role in ameliorating renal damage involved in GIAN.

La nefrotoxicidad aguda inducida por gentamicina (GIAN) se considera una de las causas importantes de insuficiencia renal aguda. En los últimos años, el gran esfuerzo se ha centrado en la introducción de la medicina herbal como un nuevo agente terapéutico para la prevención de GIAN. Por lo tanto, el estudio actual fue diseñado para investigar el efecto del extracto de grano de café verde (GCBE) sobre la GIAN en ratas. Los resultados del presente estudio mostraron que los grupos de ratas que recibieron GCBE oral durante 7 días después de la inducción de GIAN (mediante una inyección intraperitoneal diaria de gentamicina durante 7 días), informaron una mejora significativa en las pruebas de función renal en comparación con los grupos del modelo GIAN. Además, hubo una mejora significativa en los marcadores de estrés oxidativo renal (malondialdehído renal, superóxido dismutasa renal) y cambios histopatológicos renales en los grupos tratados con GCBE en comparación con el grupo del modelo GIAN. Estos resultados indican que GCBE tiene un papel potencial en la mejora del daño renal involucrado en GIAN.

The effect of gentamicin nephrotoxicity in newborn mice at breastfeeding / El efecto de la nefrotoxicidad por gentamicina en ratones recién nacidos durante la lactancia

Gentamicin can pass through the placenta. This antibiotic also enters breast milk, but its absorption in the intestine is insignificant, so that it could be only found in half of the infants' blood. In the present study, it is attempted to experimentally evaluate the toxic effect of gentamicin on the kidneys of newborn mice in breastfeeding. This study was performed on 20 female Balb/c pregnant mice weighing 30 to 35 g. The female pregnant mice were randomly divided to two groups of 10. The lactating mothers were intraperitoneally injected with gentamicin at 200 mg/kg every other day sequentially, and the normal group was injected with normal saline at the same volume. Blod samples were collected from the heart of the newborns for the evaluation of renal function. The samples were passing paraffin blocks and were staining with hematoxylin and eosin. The data were expressed as mean±SE and T-test was used. In the observations of kidney tissues of the newborns treated with gentamicin, there were several tissue injuries in comparison with the normal group such as lytic necrosis with picnotic nucleus occurred in the epithelium cells of kidney tubules. Moreover, in some epithelium cells of tubules, degeneration changes of the kind of hydropic and cytoplasmic vacuolation were observed. In the current study, though gentamicin had no significant effect on anomalies in newborns. it indicated however, that the intervention breastfeeding could have pathological effects and consequently, cause changes in the function factors of the kidneys of newborns.

La gentamicina puede pasar a través de la placenta. Este antibiótico también ingresa en la leche materna, pero su absorción en el intestino es insignificante, por lo que solo se puede encontrar en la mitad de la sangre de los recién nacidos. En el presente estudio, se intentó evaluar experimentalmente el efecto tóxico de gentamicina en los riñones de ratones recién nacidos durante la lactancia. Este estudio se realizó en 20 hembras preñadas con un peso entre 30 y 35 g. Las hembras lactantes se dividieron aleatoriamente en dos grupos de 10 animales. Las madres que amamantaron fueron tratadas con gentamicina (200 mg/kg, vía intraperitoneal), cada dos días secuencialmente, y al grupo normal se le inyectó solución salina normal en el mismo volumen. Se tomaron muestras de sangre del corazón de los recién nacidos para la evaluación de la función renal. Las muestras pasaron por bloques de parafina y se tiñeron con hematoxilina y eosina. Los datos se expresaron como media ± DE y t-test. En comparación con el grupo normal, se observaron varias lesiones en los tejidos del riñón de los ratones recién nacidos tratados con gentamicina, tal como como necrosis lítica con núcleo picnótico en las células del epitelio de los túbulos renales. Además, en algunas células del epitelio de los túbulos renales, se observaron cambios degenerativos del tipo de vacuolación hidrópica y citoplásmica. En el estudio actual, la gentamicina no tuvo un efecto significativo sobre las anomalías en los recién nacidos. Sin embargo, observamos que la intervención de amamantamiento podría tener efectos patológicos y, en consecuencia, causar cambios en los factores funcionales de los riñones en recién nacidos.

The aminoglycoside antibiotic gentamicin is able to alter metabolic activity and morphology of MDCK-C11 cells: a cell model of intercalated cells

It is well known that the aminoglycoside antibiotic gentamicin is capable of causing damage to kidney cells. Given the known involvement of Ca2+ in the nephrotoxic action of gentamicin, the purpose of this study was to establish a relationship between the concentration of intracellular Ca2+ ([Ca2+]i) and cellular cytotoxicity using MDCK-C11 cells, a clone that has several properties that resemble those of intercalated cells of the distal nephron. Changes in [Ca2+]i was determined using fluorescence microscopy. Cell viability was evaluated by the neutral red method, and cell cytotoxicity by the MTT method. The [Ca2+]i gradually increased when cells were exposed to 0.1 mM gentamicin for 10, 20, and 30 min. The presence of extracellular Ca2+ was found to be necessary to stimulate the increase in [Ca2+]i induced by gentamicin, since this stimulus disappeared by using 1.8 mM EGTA (a Ca2+ chelator). Morphological changes were observed with scanning electron microscopy in epithelial cells exposed to the antibiotic. Furthermore, with the MTT method, a decrease in metabolic activity induced by gentamicin was observed, which indicates a cytotoxic effect. In conclusion, gentamicin was able to alter [Ca2+]i, change the morphology of MDCK-C11 cells, and promote cytotoxicity.

Lack of protection against gentamicin ototoxicity by auditory conditioning with noise / Falta de proteção contra a ototoxicidade da gentamicina pelo condicionamento auditivo com ruído

INTRODUCTION: Auditory conditioning consists of the pre-exposure to low levels of a potential harmful agent to protect against a subsequent harmful presentation. OBJECTIVE: To confirm if conditioning with an agent different from the used to cause the trauma can also be effective. METHOD: Experimental study with 17 guinea pigs divided as follows: group Som: exposed to 85 dB broadband noise centered at 4 kHz, 30 minutes a day for 10 consecutive days; group Cont: intramuscular administration of gentamicin 160 mg/kg a day for 10 consecutive days; group Expt: conditioned with noise similarly to group Som and, after each noise presentation, received gentamicin similarly to group Cont. The animals were evaluated by distortion product otoacoustic emissions (DPOAEs), brainstem auditory evoked potentials (BAEPs) and scanning electron microscopy. RESULTS: The animals that were conditioned with noise did not show any protective effect compared to the ones that received only the ototoxic gentamicin administration. This lack of protection was observed functionally and morphologically. CONCLUSION: Conditioning with 85 dB broadband noise, 30 min a day for 10 consecutive days does not protect against an ototoxic gentamicin administration of 160 mg/kg a day for 10 consecutive days in the guinea pig. .

INTRODUÇÃO: O condicionamento auditivo consiste da pré-exposição de um agente lesivo em baixos níveis para proteger contra uma posterior apresentação lesiva. OBJETIVO: Confirmar se o condicionamento com um agente diferente do utilizado para causar o trauma pode ser efetivo. MÉTODO: Estudo experimental com 17 cobaias albinas divididas como a seguir- grupo Som: exposto a um ruído branco de 85 dB centrado em 4 kHz, 30 minutos por dia, por 10 dias consecutivos; grupo Cont: administração intramuscular de gentamicina 160 mg/kg por dia, por 10 dias consecutivos; grupo Expt: condicionado com ruído como o grupo Som. Após cada exposição ao ruído, recebeu gentamicina similarmente ao grupo Cont. Os animais foram avaliados por emissões otoacústicas produto de distorção (EOAPDs), potencial evocado auditivo de tronco encefálico (PEATE) e microscopia eletrônica de varredura (MEV). RESULTADOS: Os animais que foram condicionados com ruído não mostraram qualquer efeito protetor quando comparados com os que receberam apenas a gentamicina em doses ototóxicas. Esta ausência de proteção foi observada tanto funcionalmente quanto morfologicamente. CONCLUSÃO: Os autores concluíram que o condicionamento com ruído branco a 85 dB por 30 minutos, por dia por 10 dias consecutivos, não protege contra uma administração de gentamicina 160 mg/kg/dia, por 10 dias consecutivos. .

Garlic supplemented diet attenuates gentamicin nephrotoxicity ın rats

Purpose To demonstrate the effect of a 4% pulverized garlic supplemented diet on the nephrotoxicity induced by gentamicin in rats. Materials and Methods Twenty four healthy male Wistar rats, weighing between 220 - 260grams, were divided into three groups. The rats were randomly assigned to either the gentamicin injection without garlic supplementation group (Group I, n = 8), gentamicin injection with garlic supplementation group (Group II, n = 8), and control group (Group III, n = 8). Urine from the rats was collected and the volume (mL), microalbumin (mg/L), creatinine (mg/dL), Na (mmol/L), K (mmol/L), Cl (mmol/L), P (mg/dL), N-acetyl glucosamine (NAG) (U/L) and pH values were measured. Then urea (mg/dL), creatinine (mg/dL), total protein (g/dL) and cystatin (mg/L) values were measured for the blood samples obtained from tail veins. Results The median NAG value for the control group (52.050 U/L) was similar to value for Group II (56.400 U/L), which received gentamicin and the garlic diet. However, the median NAG value for Group I (77.030 U/L), which received gentamicin without garlic supplementation, was determined to be statistically significantly higher (p = 0.010) than the value for the control group. In addition, the mean cystatin value for Group II (1.360 U/L) was found to be statistically significantly lower than the value for the Group I (2.240 U/L) (p = 0.015). Conclusions In this study we showed the effect of 4% pulverized garlic supplemented diet for preventing nephrotoxicity induced by gentamicin in rats by using as parameters NAG in urine samples and cystatin C in serum samples. .

Protective effect of curcumin and gingko biloba l. extract against gentamicin-induced nephrotoxjcity in rats

Gentamicin [GENT] which is a commonly used antibiotic causes nephrotoxicity in man and animals. Generation of free radicals in the renal cortex plays an important role in the pathogenesis of gentamicin-induced nephrotoxicity in rats. Curcumin, the yellow curry pigment isolated from turmeric [the ground rhizome of Curcuma longa L] and Ginkgo biloba extract have been reported to possess antioxidant and free radical scavenging properties. The present study was designed to investigate the potential protective role of curcumin, Ginkgo biloba extract, and their combination on gentamicin-induced nephrotoxicity in rats. The rats were divided into six groups, 8 animals each. Group 1 rats were treated with GENT [80 mg/kg/day] IM for 6 days. Rats of groups 2, 3, and 4 "were pretreated orally for 4 days with curcumin [200 mg/kg/day], Ginkgo biloba leaf extract [300 mg/kg/day], and a combination of curcumin and Ginkgo biloba leaf extract, respectively before concomitant administration of GENT for additional 6 days. Control groups of animals were treated with pure vehicles IM or orally. Nephrotoxicity was evaluated biochemically and histopathologically. Treatment of rats with GENT produced elevation in serum creatinine, urea levels and severe tubular necrosis. Concomitantly, treatment of rats with GENT produced elevation in serum nitrite level, decrease in renal intracellular reduced glutathione [GSH] level and superoxide dismutase [SOD] activity. Pretreatment of rats with curcumin, Ginkgo biloba extract, or their combination decreased GENT-induced disturbances in kidney function and structure. In addition, pretreatment of rats with curcumin, Ginkgo biloba extract, or their combination decreased GENT-induced alterations in serum nitrite level, renal intracellular GSH level and SOD activity. The combined treatment was more effective than either agent alone. These results indicate that curcumin, Ginkgo biloba extract, or their combination has the ability to protect against GENT-induced nephrotoxicity. Inhibition of oxidative stress and nitric oxide production may play an important role in these protective effects

Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin

Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H2S) is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H2S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8) were injected with 40 mg/kg gentamicin (im) twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg-1·day-1, ip). Control rats (N = 6) were treated with saline or PAG only (N = 4). Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H2S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87) mg percent] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00)] in the renal cortex. These changes were associated with increased H2S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein-1·h-1) compared to control (21.12 ± 1.63) and PAG (11.44 ± 3.08). Treatment with PAG reduced this increase (171.60 ± 18.34), the disturbances in plasma creatinine levels [2.20 (1.92; 4.60) mg percent], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00)]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H2S formation.

Nephroprotective and nitric oxide scavenging activity of tubers of momordica tuberosa in rats

Hydroalcoholic extract [70% ethanol extract] of tubers of Momordica tuberosa Cogn. [Cucurbitaceae] was subjected to preliminary phytochemical screening by qualitative tests. Nitric oxide scavenging activity was performed by Griess reagent method. And nephroprotective activity was assessed in gentamicin, cisplatin and paracetamol induced renal damage in wistar rats [150-200 g] by standard methods. The protective property of 70% ethanol extract was assessed by measuring the levels of body weight, blood urea, serum creatinine, tissue glutathione and lipid peroxidation in administered doses. The extract exhibited free radical scavenging activity in dose dependant manner. And 100 micro g/ml dose produced significantly higher scavenging activity than standard sodium metabisulphate at 25 micro g/ml. Also, it significantly reduced the renal damage caused by cisplatin, gentamicin and paracetamol at a dose of 40 mg/kg

Comparative nephrotoxic effects of gentamycin and tobramycin

To compare the nephrotoxic effects of two aminoglycosides namely, gentamycin and tobramycin on rabbits. Comparative study. Allama Iqbal Medical College Lahore, from January 2010 to December 2010. The serum levels of creatinine and electrolytes [sodium and potassium] were measured in different groups of rabbits [control group-A, gentamycin group B and tobramycin-group C]. Rabbits in group B and C received laboratory diet and 32 mg/kg/day of gentamycin and tobramycin were given through intramuscular [IM] route twice daily for 7 days. Blood samples were collected on day 1, 10, 16, and 22 of drug administration. Each rabbit of all groups was sacrificed on 22[nd] day of experiment. Kidneys were removed and histological examination of the 4 components of the renal tissue [glomeruli, tubules, blood vessels and interstitial tissue] was carried out. Level of serum creatinine was significantly increased in both experimental groups [B and C] as compared to the control group A. On the other hand, level of serum sodium was insignificantly increased in groups B and C, whereas level of serum potassium was significantly decreased in groups of rabbits receiving gentamycin and tobramycin as compared to control group. There was no significant difference in nephrotoxicity between gentamycin and tobramycin

Cocleotoxicidade da gentamicina por doses habituais para neonatos - estudo funcional / A functional study on gentamicin-related cochleotoxicity in its conventional dose in newborns

A identificação precoce das alterações auditivas possibilita a intervenção ainda no "período crítico" e ideal de estimulação da linguagem e da audição. A ototoxicidade infantil é um tema bastante controverso. Têm sido relatadas percentagens variáveis de casos de ototoxicidade em crianças com vários antibióticos aminoglicosídeos. Os principais grupos pediátricos que recebem antibióticos aminoglicosídeos são recém-nascidos com infecções graves na UTI neonatal. Objetivos: Verificar o aspecto funcional das células ciliadas externas da cóclea a esquemas terapêuticos utilizados para o tratamento de infecções no período neonatal. Forma de estudo: Experimental. Material e método: Foram estudadas 26 cobaias albinas, através das emissões otoacústicas por produto de distorção, prévia e posteriormente a aplicação de gentamicina. Resultados: Em todas as avaliações, o estado funcional das células ciliadas externas, estudadas pelas emissões otoacústicas por produto de distorção, mostraram-se preservadas. Conclusão: Neste experimento não foram observadas alterações no funcionamento das células ciliadas externas de cobaias albinas sob tratamento com gentamicina nas doses de 4 mg/Kg/dia e 2,5 mg/Kg/dia a cada 12 horas, por 10 e 14 dias.

The early identification of hearing impairment allows for an intervention still in the "critical" and ideal period of hearing and language stimulation. Pediatric ototoxicity is a very controversial topic. There have been variable percentages of ototoxicity cases in children with different aminoglycosides antibiotics. The main pediatric groups whom receive aminoglycosides are newborns with severe infections on the neonatal ICU. AIM: to check the functional aspect of the cochlear external hair cells and treatment regimens used to treat infections during the neonatal period. Study Design: Experimental. Materials and Methods: we studied 26 albino guinea pigs, through distortion product otoacoustic emissions, before and after the use of gentamicin. Results: in all the assessments, the external hair cells functional status, studied by means of the distortion product otoacoustic emissions, proved preserved. Conclusion: In the present study, we did not notice changes in outer hair cell function in the albino guinea pigs treated with gentamicin in the doses of 4 mg/Kg/day and 2.5 mg/Kg/day every 12 hours for 10 and 14 days.

Efeito de fármacos ototóxicos na audição de recém-nascidos de alto risco / Effects of ototoxic drugs in the hearing of high risk newborns

OBJETIVOS: Calcular a incidência da perda auditiva sensorioneural (PASN) em recém-nascidos de alto risco, verificar se existe associação causal entre o uso de fármacos ototóxicos em neonatos de alto risco e a PASN e estabelecer a frequência das mutações genéticas relacionadas à PASN em neonatos de alto risco. MÉTODOS: A pesquisa foi uma coorte retrospectiva e prospectiva realizada em 250 crianças. Foi realizada coleta de dados em prontuários e com os responsáveis, triagem auditiva por emissões otoacústicas-produto de distorção, timpanometria, audiometria com reforço visual, potencial evocado auditivo de tronco encefálico e emissões otoacústicas transientes. A pesquisa das mutações genéticas 35delG e mitocondriais A1555G e A7445G, foi fundamental para avaliar a possibilidade da PASN ser de origem genética não-sindrômica. RESULTADOS: A incidência da PASN foi de 11,6 por cento, as associações causais entre a PASN e os fármacos administrados foram: amicacina e cefotaxima (OR 5,35), cefotaxima e furosemida (OR 7,02), ceftazidima e vancomicina (OR 9,12). A frequência da mutação 35delG foi de 0,8 por cento e para as mutações mitocondriais A1555G e A7445G foi 0 por cento. CONCLUSÃO: A incidência de PASN em recém-nascidos de alto risco foi alta, apresentando importante relação causal com o uso de medicamentos e pequena relação com mutações genéticas.

PURPOSE: To calculate the incidence of sensorineural hearing loss (SNHL), to verify if there is a causal association between the use of ototoxic drugs and SNHL, and to establish the frequency of genetic mutations related to SNHL in high risk newborns. METHODS: The study was a retrospective and prospective cohort research with 250 children. Data was gathered from subjects' charts and with their caregivers. Moreover, subjects were submitted to auditory evaluation with distortion product otoacoustic emissions, timpanometry, visual reinforcement audiometry, auditory brainstem response and transient otoacoustic emissions. The study of the genetic mutation 35delG, and the mitochondrial mutations A1555G and A7445G was essential to evaluate the possibility that SNHL had a non-syndromic genetic origin. The association between the medicine use and the occurrence of hearing loss had been analyzed. RESULTS: The incidence of SNHL in high risk newborns was 11.6 percent, and causal associations between SNHL and the drugs administered were: amikacin and cefotaxime (OR=5.35), cefotaxime and furosemide (OR=7.02), ceftazidime and vancomycin (OR=9.12). The frequencies of the mutation 35deIG and mitochondrial mutations A1555G and A7445G were, respectively, 0.8 percent and 0 percent. CONCLUSION: The incidence of SNHL in high risk newborns was high, showing an important causal relation with the use of ototoxic drugs and a small relation with genetic mutations.

Effect of crocus sativus on gentamicin induced nephrotoxicity

Crocus sativus, known as saffron, is used in folk medicine for treatment of different types of diseases, and its anti-inflammatory and free radical scavenging activities have been demonstrated. The present study evaluated gentamicin nephrotoxicity in saffron treated rats. Male Wistar rats (200-250g) were treated with saffron (40 or 80 mg/k/d) for 10 days, or saffron (40 or 80 mg/ kg/d) for 10 days and gentamicin 80 mg/kg/d for five days, starting from day 6. At the end of treatment, blood samples were taken for measurement of serum creatinine (SCr) and BUN. The left kidney was prepared for histological evaluation and the right kidney for Malondialdehyde (MDA) measurement. Gentamicin 80 (mg/k/d) increased SCr, BUN and renal tissue levels of MDA and induced severe histological changes. Saffron at 40 mg/k/d significantly reduced gentamicin-induced increases in BUN and histological scores (p<0.05). Gentamicin-induced increases in BUN, SCr and MDA and histological injury were significantly reduced by treatment with saffron 80 mg/k/d (p<0.05, p<0.001, p<0.05, and p<0.001 respectively). In conclusion, our results suggest that saffron treatment reduces gentamicin-induced nephrotoxicity and this effect seems to be dose dependent.

Zingiber officinale protective effects on gentamicin's toxicity on sperm in rats

Ginger rhizome [Zingiber officinale R., family: Zingiberaceae] is used medicinally and as a culinary spice and has anti-oxidant and cell-protective effects in animals and humans body. The aim of this study was to investigate the influence of ginger rhizome toxicity of gentamicin on sperm parameters in male rats. Forty Wistar male rat [n=40] were allocated into four groups, control [n=10] and test groups [n=30], that subdivided into groups of 3 that received ginger rhizome powder [100 mg/kg/day], gentamicin group that received, 5 mg/kg/day and ginger group that received, 5 mg/kg/day gentamicin additionally, for 30 consequence day. Animals were kept in standard conditions. In thirty day the testes tissue of rats in whole groups were collected. Ginger administration caused a marked increase in the testosterone concentrations of the rats even in spite of receiving 5 mg/kg/day gentamicin in compared with the control and gentamicin treated groups. Ginger rhizome is able to overcome reproductive toxicity of gentamicin and induces spermatogenesis probably mainly through the elevation of testosterone levels

effect of thymoquinone on the activities of drug metabolizing enzymes following gentamicin - induced nephrotoxicity in rats

The present study investigated the effects of thymoquinone on the renal activities of drug-metabolizing enzyme following gentamicin-induced nephrotoxicity in Wistar breed rats. Intraperitoneal administration of thymoquinone alone in rats at the dose rate of 10 mg/kg daily for ten consecutive days did not produce toxic effects in the kidney or change its drug metabolizing capacity. However, nephrotoxicity was produced in Rats injected intraperitoneally with gentamicin daily at the dose rate of 80 mg/kg body weight for ten consecutive days, where there was significant increase in the concentrations of serum creatinine and blood urea compared to control rats [P < 0.0005] and those treated with thymoquinone alone [P < 0.0005], or those given thymoquinone and gentamicin concomitantly [10 mg/kg and 80 mg/kg intraperitoneally daily for ten consecutive days, respectively] [P < 0.0005]. In addition, injection of gentamicin illustrated a tendency to decrease, although not statistically significant, in the kidney concentration of reduced glutathione. Furthermore, gentamicin administration resulted in a significant decrease in the renal concentration of cytochrome P-450 [P < 0.05], while it could not produce significant changes in the renal activities of phase II drug metabolizing enzymes namely, UDP-glucuronyltransferase and glutathione-S-transferasc compared to values obtained for control rats and those treated with thymoquinone alone or coadministered with gentamicin. These findings confirm the nephrotoxic effects of gentamicin and its ability to decrease the renal activities of phase I drug metabolizing enzymes as shown by the significant reduction in the concentration of cytochrome P-450 in the kidneys of treated rats. It can be concluded that thymoquinone coadministration with gentamicin can induce protective effects against gentamicin nephrotoxicity accompanied with restoration of the concentration of cytochrome P-450 to normal levels in the kidneys of treated rats

Determination of the effects of ciprofloxacin in prevention of aminoglycoside induced nephrotoxicity in rabbits: a comparative study

The effect of ciprofloxacin on gentamicin-induced nephrotoxicity was evaluated in rabbits. Animals were injected for 15 days with saline [NaCI; 0.9%], gentamicin alone at doses of 20 mg/kg of body weight/12 h [intramuscularly] and the combination of gentamicin [20 mg/kg/12 h] with low and high therapeutic doses of ciprofloxacin [20 mg/kg/12 h and 40 mg/kg12h respectively] by intraperitoneal route. Gentamicin induced nephrotoxicity was evaluated by histopathological and serum analysis. The extent of these changes were significantly increased when gentamicin was given in combination with ciprofloxacin both in low and high doses. although the mechanisms by which ciprofloxacin enhances the nephrotoxic potential of gentamicin are unknown, it is proposed that ciprofloxacin induced allergic interstitial nephritis, enhances the nephrotoxicity and it was indicated by increased amount of interstitial inflammatory infiltrate in the renal proximal tubules of the animals treated with ciprofloxacin-gentamicin combination

Gentamicin induces renal morphopathology in Wistar rats / Gentamicina induce morfopatología renal en ratas Wistar

Due to its prominent role in major excretory pathways, the kidney is particularly sensitive especially to toxicity for antimicrobials drugs. Storage of these drugs in the renal cortex, their effect on renal cells, have consequences on the renal function, and then reabsorbed by renal tubules induce nephrotixicity. Our objective was to show the renal morphopatological alterations induced by gentamicin through the histochemical methods of routine periodic acid de Schiff (PAS) staining and imunohistochemical staining for the expression of the protein P53, which is considered as a marker for cellular apoptosis. This allows the early detection of tubular lesions. The renal morphopathologic findings were cell apoptosis, basal membrane interruption, mesangial proliferation cells, decreased Bowman's space. This result clearly shows that gentamicin administration induces renal morphopatological alterations.

Debido a su importante rol en la función de excreción mayor, el riñon es especialmente propenso a la toxicidad por los antibióticos bactericidas. La acumulación de los antibióticos aminoglicosidos en la corteza renal tiene como consecuencia efectos en las células renales y en la función renal y cuando son reabsorbidos por los túbulos renales, pueden conducir a toxicidad renal. Nuestro objetivo fue mostrar alteraciones morfopatológicas renales causadas por la administración de gentamicina, a través de métodos histoquímicos de rutina con ácido periódico de Schiff (PAS) y tinción inmunohistoquímica para la expresión de la proteína P53, la cual es considerada como un marcador para la apoptosis celular, permitiendo la detección precoz de lesiones tubulares. Los resultados morfopatológicos renales fueron apoptosis celular, interrupción de la membrana basal, proliferación de células mesangiales y disminución del espacio de Bowman. Los resultados mostraron claramente que la administración de gentamicina induce alteraciones morfopatológicas renales.

Can aspirin protect or at least attenuate gentamicin ototoxicity in humans?

To investigate and prove that Aspirin as an antioxidant protects, or at least attenuates Gentamicin ototoxicity in humans. A prospective, randomized, double-blind trial was conducted in 60 patients that completed all requirements. This study was conducted in the Department of Otolaryngology and Orthopedics, Besat Hospital, Hamadan University of Medical Sciences, Hamadan, Iran, between December 2007 and November 2008. The patients were divided into 2 groups, the experimental and the control groups that were similar with respect to gender, age, and weight. The treatment group received 1.5 g/day [500 mg every 8 hours] Aspirin, and the control group received placebo similar to the other group. Comparison of the pure tone audiometry [PTA] at 1000 Hertz [Hz] [p=0.03], 2000 Hz [p=0.003], 4000 Hz [p=0.001], and 8000 Hz [p=0.0010] showed significant differences between mean of PTA at the beginning, 8th, and 15th day. The threshold of PTA at 250Hz was significantly different only at the 8th and 15th day [p=0.004], also at the frequency of 500Hz, the difference between the beginning within 15th day and 8th day with 15th day was significant [p=0.001]. In the present study, we had shown that Aspirin can protect the ototoxic effect of gentamicin in patients

Dose-dependent amelioration of gentamicin-Induced nephrotoxicity in adult swiss albino rats by vitamin B-complex - A preliminary study

Purpose: To evaluate the effect of vitamin B-complex on the nephrotoxicity of gentamicin in an established rat model. Methods: Adult Swiss albino rats weighing 170±20g were divided into 4 groups of 4 rats each. Each group was given one of the following: placebo injection (Control), 80mg/kg of gentamicin sulphate alone or with 1.5ml/kg/3ml/kg body weight of vitamin B-complex (intramuscular) containing 10mg thiamine, 1.5mg riboflavin and 1.0mg pyridoxal-6-phosphate per ml. Results: In the Swiss albino rats, daily intramuscular 80mg/kg gentamicin sulphate significantly (p<0.05) and consistently produced biochemical signs of nephrotoxicity after 5 days. Also, 1.5 ml/kg of B-complex significantly (p<0.05) ameliorated the rate and extent of increase in serum urea and creatine while 3ml/kg of the same drug completely prevented the increase in serum urea and creatine in this model. Conclusion: Vitamin B-complex dose-dependently ameliorated gentamicin-induced nephrotoxicity in adult Swiss albino rats when given intramuscularly. This finding may have important clinical utility

Protective effect of taurine and quercetin against renal dysfunction associated with the combined use of gentamycin and diclofenac.

The potential protective effects of taurine and quercetin against gentamycin (GM)/diclofenac (DC) combined nephrotoxicity were investigated in rats. The results showed that administration of DC alone at an oral dose of 5 mg/kg b.wt/day for 28 days had no significant effect on the measured parameters, except for marked increase in urinary uronic acid excretion. Administration of GM alone at a dose of 100 mg/kg b.wt/day i.p. for 8 days resulted in obvious nephrotoxicity. Combined GM-DC treatment led to the most pronounced nephrotoxicity, as indicated by greater elevations in serum urea, creatinine and urinary N-acetyl-beta-D-glucosaminidase (NAG), together with severe depression of renal cortical Na , K+-ATPase, compared to GM-treated group. Moreover, only combined treatment resulted in significant decrease in urinary potassium and renal cortical glutathione peroxidase (GSHPx), together with an increase in renal cortical lipid peroxidation products (LPOs). Co-administration of taurine or quercetin normalized creatinine clearance and ameliorated the elevations in urinary proteins, uronic acids, NAG and renal cortical LPOs in GM/DC treated rats. The study justifies the use of taurine and quercetin as renoprotective agents against the nephrotoxicity caused by GM/DC therapy.