Gentamicin-induced Nephrotoxicity Research Articles

Ameliorative Effects of Zataria Multiflora Hydro-Alcoholic extract on Gentamicin Induced Nephrotoxicity in Rats.

Nephrotoxicity is the major side effects of aminoglycoside antibiotics such as gentamicin. The aim of this study was to investigate the therapeutic effects of Z.multiflora (ZM) hydroalcoholic extract on gentamicin-induced nephrotoxicity. Twenty-eight male Wistar rats categorized into four groups: 1) the control group without injection, 2) the gentamicin treated group (100 mg/kg, i.p) 3) the gentamicin and Z. Multiflora treated group; Z. Multiflora extract(0.8 mg/ml in the drinking water) administered after gentamicin (100 mg/kg, i.p) 4) the normal saline and Z. Multiflora treated group; Z. Multiflora extract (0.8 mg/ml in the drinking water) administered after normal saline injection (2 ml/kg,i.p ). Post-treatment with ZM extract caused a significant reduction in the levels of plasma creatinine and blood urea nitrogen (BUN), absolute and fractional excretion of sodium, malondialdehyed (MDA) level in comparison to gentamicin group. In addition, ZM extract significantly increased creatinine clearance, urine osmolarity, and Renal blood flow (RBF) and the Ferric reducing ability of plasma (FRAP) level which had decreased compared to the control group as a result of treatment with gentamicin. The above result indicated that ZM extract improved renal toxicity of gentamicin via reducing oxidative stress, oxygen-free radicals, and lipid peroxidation.

Ameliorative effect of ferulic acid on gentamicininduced nephrotoxicity in a rat model; role of antioxidant effects

Introduction: The nephrotoxicity of gentamicin is thought to be a dangerous side effect in the use of this drug caused by the formation of oxidative stress and the production of reactive oxygen species (ROS) and nitrogen species. Antioxidant agents play important roles in reducing oxidative stress. Objectives: In this study, the antioxidant role of ferulic acid has been studied in nephrotoxicity caused by gentamicin. Materials and Methods: In this experimental study, 50 Spraque-Dawley rats were randomly divided into 5 groups. The first group was considered as the control group and other groups received different doses of ferulic acid + 80 mg/kg gentamycin for 8 days by intraperitoneally injection. After the treatment, blood samples were prepared from animals. Then, the right and left kidneys were removed, paraffin blocks prepared, and the rest of the tissues were lysed. Three samples were used to evaluate serum creatinine and urea, as well as urine creatinine, histopathologic status and oxidative stress factors levels, respectively. To compare the results of different groups, Mann-Whitney U test was used. Results: Ferulic acid treatment decreased tissue malondialdehyde (MDA), serum urea and creatinine, urine albumin/creatinine ratio and neutrophil gelatinase-associated lipocalin (NGAL), and also increased superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT). Ferulic acid reduced tubular necrosis and eosinophilic casts in gentamycin group induced nephrotoxicity. Conclusion: Ferulic acid can be effective in inhibiting gentamicin-induced nephrotoxicity.

Effects of Pituitary Adenylate Cyclase Activating Polypeptide in Human Proximal Tubule Cells Against Gentamicin Toxicity

Nephrotoxicity by aminoglycoside antibiotics is a common cause of drug-induced nephropathy. Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide first isolated from hypothalamus, but later shown in widespread distribution. It exerts general cytoprotective effects in different cell types. Renoprotective effects of PACAP have been shown in various in vivo and in vitro experiments, but it is still not known whether it protects human proximal tubular cells against gentamicin toxicity. The aim of the present study was to investigate whether PACAP could influence the survival rate of human proximal tubular epithelial cells exposed to gentamicin treatment. For investigating its effect on cell survival after gentamicin treatment, cell viability was evaluated using MTT assay. Obtaining further insight into the background mechanism of gentamicin exposure and PACAP’s effect, expression of numerous kidney-related proteins was investigated using kidney biomarker array. Our results show that PACAP had protective effects against gentamicin-induced decreased cell viability, while it did not influence the proliferation activity of HK-2 cells. PACAP could counteract the expression-decreasing effect of gentamicin on dipeptidyl peptidase IV and vascular endothelial growth factor as assessed by kidney biomarker array. In summary, our present study could prove the protective effect of exogenous PACAP in gentamicin-induced nephrotoxicity.

Effect of caffeic acid phenethyl ester (CAPE) on vascular endothelial growth factor a (VEGF-A) gene expression in gentamicin-induced acute renal nephrotoxicity

Vascular endothelial growth factor-A (VEGF-A) gene expression in an experimental gentamicin-induced nephrotoxicity and ameliorative effect of caffeic acid phenethyl ester (CAPE) was investigated in rats. Animals were divided into four groups (n=8); control (C) group animals were given 10% dimethylsulfoxide (DMSO); gentamicin (G) group animals were given 100 mg/kg/day gentamicin; CAPE group animals were given 30 mg/kg/day CAPE and CAPE+G group animals were given 100 mg/kg/day gentamicin plus 30 mg/kg/day CAPE. Serum creatinine and BUN levels significantly increased in gentamicin group as compared to the control group (p0.05). Gene expression level of VEGF-A in gentamicin group significantly decreased as compared to the control group, however, CAPE treatment did not have any increasing effect on the gene expression level. According to histopathological investigation, gentamicin treatment caused prominent degeneration in kidney tissue and CAPE treatment had only slight beneficial effect on lowering the tissue degeneration. The results showed that gentamicin decreases VEGF-A gene expression and this might be related to the tissue degeneration at cellular level. However, CAPE treatment did not have significant ameliorative effect in lowering the gentamicin induced nephrotoxicity.

The Protective Effect of Sika Deer Antler Protein on Gentamicin-Induced Nephrotoxicity in Vitro and in Vivo

Background/Aims: Sika deer (Cervus nippon Temminck) antler is traditional animal medicine of renal protection in East Asia. This study measured the effect of sika deer antler protein (SDAPR) on gentamicin (GM)-induced cytotoxicity in HEK293 cells, and investigated the effect of SDAPR against GM-induced nephrotoxicity in mice. Methods: HEK293 cells viability and oxidative stress were measured in HEK293 cells while flow cytometry was used for apoptosis analysis. The acute kidney injury biomarkers, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and cystatin c (Cys-C), were repeatedly measured by ELISA assay. ICR male mice were randomly assigned six groups: Control, GM with vehicle, single SDAPR, GM with SDAPR at three concentrations 50, 100, 200 mg/kg/d, p.o., 10 d. GM was injected for 8 consecutive days (100 mg/kg/d, i.p.). Renal function, oxidative stress and levels of inflammatory factors were measured in vivo. Renal tissues were stained with H&E to observe pathological changes. Results: Pretreatment with SDAPR (0.5-4.0 mg/mL) significantly improved cell viability. Treatment with SDAPR could reduce KIM-1, NGAL and Cys-C activity. SDAPR could improve antioxidant defense and attenuated apoptosis on HEK293 cells. SDAPR also ameliorated GM-induced histopathologic changes, and decreased blood urea nitrogen (BUN) and serum creatinine (Cr). Additionally, SDAPR significantly regulated oxidative stress marker and interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) inflammatory cytokines. Conclusion: These results show that SDAPR could be an effective dietary supplement to relieve GM-induced nephrotoxicity by improved antioxidase activity, suppressed inflammation, and inhibited apoptosis in vitro and vivo.

Protective Effects of Tomato Lycopene and Zingiber officinale Extracts on Gentamicin-induced Nephrotoxicity in Adult Albino Rats (Comparative study)

Gentamicin (GEN) is an aminoglycoside antibiotic that is widely used in treatment of gram negative bacterial infections. Tomato lycopene (LYC) and Zingiber officinaleethyl acetate extract (ZOEAE) are powerful antioxidants against free radicals and oxidative attacks. Aim of the work was to investigate the protective effects of tomato LYC and ZOEAE against GEN induced oxidative stress and apoptosis on kidney of adult albino rats. Material and methods: the study was conducted for 10 days on 72 adult albino rats of both sexes, divided into six main groups; one control (subdivided into 4 subgroups) and five treated groups (8 rats in each subgroup & group). Apart from Group І(control groups) the treated groups are treated as follow: Group ІI (LYC) treated orally with LYC (200 mg /kg/day). Group ІII (ZOEAE) treated orally with ZOEAE (200 mg /kg/day). Group IV (GEN) treated with IP injection of GEN (67.4 mg/kg/day). Group V (GEN + LYC) treated with GEN (67.4 mg/kg/day) along with LYC (200mg/kg/day). Group VI (GEN + ZOEAE) treated with GEN (67.4 mg /kg/day) along with LYC (200 mg/kg/day). All animals were sacrificed 24 hours after the last dose, their blood and kidney tissues were subjected to biochemical analysis, while the remaining kidney tissues were stained for histopathological study. Results: GEN administration for 10 days significantly increased serum urea and creatinine concomitant with marked renal histopathological changes, suggesting nephtotoxicity. Also, it significantly increased renal malondialdehyde and decreased renal reduced glutathione and catalase activity, suggesting free radical formation. GEN also caused DNA fragmentation, suggesting apoptosis. Co-administration with either tomato LYC or ZOEAE produced approximate comprehensive improvements of all studied parameters with the superiority of ZOEAE as regard histopathology. Recommendations: Supplementation with antioxidants e.g. LYC and ZOEAE in GEN treated patients had beneficial impacts through alleviating the oxidative stress and improving renal functions

Sex Difference in Gentamicin-induced Nephrotoxicity: Influence of L-arginine in Rat Model.

Background:L-arginine is an important precursor for the formation of nitric oxide (NO). According to previous studies, NO function is related to gender. Likewise, chronic renal diseases have lower prevalence in female. Gentamicin (GM) is an aminoglycoside antibiotic. According to some studies, males are more sensitive to GM renal nephrotoxicity. This study attempts to find protective effects of L-arginine on GM nephrotoxicity in male and female rats.Methods:Male and female rats were divided into eight groups: Rats were randomly assigned to 8 groups each including both male and female rats. The first and second groups received vehicle (saline), the third and fourth groups received gentamicin (80 mg/kg), the fifth and sixth groups received L-arginine (150 mg/kg), and finally, seventh and eighth groups received gentamicin+ L- arginine. Next, 9 days after administering drugs, blood samples were collected from the heart. After making sacrifices, the level of blood urea, creatinine (Cr), nitrite, and malondialdehyde (MDA) was measured in serums. Likewise, nitrite and MDA were measured in the homogenized kidney tissue.Results:GM significantly increased serum level of urea and Cr in male and female rats (P < 0.05). However, co-administration of GM + L-arginine significantly did not decrease urea and Cr level in male rats, whereas, in female rats, they significantly reduced (P < 0.05). In response to GM, renal MDA level increased in male and female rats (P < 0.05), and in the presence of GM + L-arginine, the level of MDA significantly decreased in both genders (P < 0.05).Conclusions:L-arginine demonstrated some protective effects in female rats but did not protect against GM nephrotoxicity in male rats for unknown reasons, probably related to the effects of sex hormones which needs further studies to be confirmed.

Protective effect of nebivolol on gentamicin-induced nephrotoxicity in rats.

Nephrotoxicity is a major complication of gentamicin (GEN), which is widely used in the treatment of severe Gram-negative infections. As we know, treatment with nebivolol has been shown to decrease renal fibrosis and glomerular injury as well as improve endothelial dysfunction. Therefore, we evaluated the potential protective effect of nebivolol (NBV) against GEN-induced nephrotoxicity in rats. Twenty-four rats were randomly divided into four groups: control group (Group 1); rats intraperitoneally injected with GEN (100 mg/kg/day; Group 2); rats treated with GEN plus distilled water (Group 3); and rats treated with GEN plus NBV (10 mg/kg/day; Group 4). After 15 days, the rats were sacrificed, their kidneys taken, and blood analysis performed. Tubular necrosis and interstitial fibrosis scores were determined histopathologically in a part of kidneys; nitric oxide (NO), malondialdehyde (MDA), and reduced glutathione (GSH) levels were determined in other part of kidneys. The GSH levels in renal tissue of only GEN-treated rats were significantly lower than those in control group, and administration of NBV to GEN-treated rats significantly increased the level of GSH. The group that was given GEN and NBV had significantly lower MDA and NO levels in kidney cortex tissue than that given GEN alone. Despite the presence of mild tubular degeneration, the rats treated with GEN+NBV showed a less severe tubular necrosis, and their glomeruli maintained a better morphology compared to GEN group. NBV exerts antioxidant, anti-inflammatory and antifibrotic effects on GEN-induced kidney damage by reducing oxidative stress in rat model (Tab. 3, Fig. 2, Ref. 68).

Pumpkin and Vitamin E as Potent Modulators of Apoptosis in Gentamicin-induced Rat Nephrotoxicity

Pumpkin and Vitamin E as Potent Modulators of Apoptosis in Gentamicin-induced Rat Nephrotoxicity

Nitric oxide metabolite changes in gentamicin-induced nephrotoxicity; the effects of antioxidant vitamins

Introduction: Nitric oxide (NO) has some important roles in endothelial functioning and renal hemodynamics. Based on previous studies, NO function is different in both genders. Probably, antioxidant vitamins, as free radical scavengers, have some protective effects on renal injury. Objectives: This study aims to search the possible antioxidant effects on nitrite level in both sexes. Materials and Methods: The rats were divided into 8 groups each including both male and female ones; The categories include 1) gentamicin treated, 2) gentamicin and vitamin E-treated, 3) gentamicin and vitamin C-treated, 4) gentamicin plus vitamin E and C treated. Nine days after administering drugs, blood samples were collected from the heart. The level of urea, creatinine (Cr), and nitrite were measured in the animals serum. Also, nitrite level was measured in the homogenized kidney tissue. Results: Gentamicin, in male and female rats enhanced serum urea and Cr levels significantly at the level of P<0.05. In the presence of the vitamins E and C individually urea and Cr levels decreased significantly too. After GM administration serum nitrite level was higher in female than male rats at the statistically significant level. Vitamin E increased serum nitrite level in male and female rats in comparison with GM group. Similarly, the vitamins enhanced kidney nitrite level which was significantly higher in male than female animals. Conclusion: This study shows that administrating vitamin E and C could individually have stronger effect on nitrite more prominently among male rats.

The Protective Effect of Acacia senegal gum against Gentamicin-Induced Nephrotoxicity In Albino Rats

Introduction: Acacia senegal gum is commonly known as Arabic gum or gum Arabic(GA) which obtained from the branches and stems of the trees as a dried gummy exudates. It is widely used in food and pharmaceutical industries as emulsifier and suspending agent. It has many pharmacologic effects including gastrointestinal effects such as increasing the short chain fatty acids and enhance water and electrolytes intestinal absorption but variable effects on lipid metabolism. In chronic renal failure patients, gum arabic reduces serum urea nitrogen. It is a potent superoxide scavenger so that it have a good protective activity against acetaminophen-induced hepatotoxicity and doxorubicin-induced cardiotoxicity in rats. The Aim of study: In the present study, we investigated the protective effect of Acacia senegal gum against gentamicin (GM)-induced nephrotoxicity in male albino rats. Materials and Method: The animals were divided into three groups A (Control), B (GM-only treated rats, 80mg/Kg, IM for 7days) and C (GA 10g/100ml water, orally for 4weeks prior to GM treatment). The nephrotoxicity was evaluated biochemically by determination level of serum Creatinine (Crea), Urea (Urea) and Uric acid (UA) level and histologically by microscopic examination the degree of proximal tubular damage. Results: The results showed significant increase in the level of Crea, Urea and UA in animals treated with GM only. In group (C), the level of Crea was high significant compared with the control but the level of Urea was significantly decreased compared with the control and the level of UA was significantly decreased compared with group B but higher than the control. Conclusion: These results suggest that Acacia senegal gum has some nephroprotective in rats, may be due to its antioxidant activities of GA.

Hyperbaric oxygen treatment and nephrotoxicity induced by gentamicin in rats

BackgroundNephrotoxicity is a significant adverse side effect of gentamicin. Previous preclinical studies showed that hyperbaric oxygen treatment (HBOT) may have beneficial effects by attenuating renal damage in rats subjected to renal injury. We evaluated the effect of HBOT on acute renal failure caused by gentamicin.MethodsThirty-six rats were divided into four groups. Gentamicin (150 mg/kg for 5 consecutive days) was administered in 30 rats, 10 rats received only gentamicin, 10 rats received 100% oxygen therapy on days 1-5 of the experiment, 10 received daily HBOT on days 1-5 of the experiment, and the remaining six served as a control group. On day 6, renal function tests and renal pathological examinations were performed.ResultsBody weight and biochemical parameters were similar in all groups except for higher plasma levels of calcium in the 100% oxygen group (P = 0.03). All the rats in the experimental group showed biochemical parameters compatible with renal failure (high serum levels of urea and creatinine). All the rats in the control group had normal renal function tests. Two rats from the HBOT group died on the fifth day of the experiment. All rats in the control group demonstrated normal renal morphology. All 28 intoxicated rats showed moderate to severe histopathological changes without significant differences between the groups.ConclusionsTreatment of gentamicin-induced nephrotoxicity with either HBOT or 100% oxygen for 5 days had no beneficial renal effect. Mortality was observed only in the HBOT group.

Ameliorative effects of gallic acid on gentamicin-induced nephrotoxicity in rats

The major side effect of gentamicin (GEN) is nephrotoxicity which in turn restricts the clinical use of this drug. In this study, the effect of gallic acid (GA) on gentamicin-induced nephrotoxicity was studied. A total number of 28 male Wistar rats were randomly divided into four experimental groups: control, GEN (100 mg/kg/day), GEN + GA (30 mg/kg/day), GA (30 mg/kg/day). All drug administrations were done intraperitoneally (i.p) for eight consecutive days. Twenty-four hours after the last administration, blood samples were collected to determine serum creatinine (Cr), blood urea nitrogen (BUN). The right kidney was used for histological examination. Malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity were assayed in left renal tissue. Results showed a significant increase in the levels of MDA, NO, Cr, and BUN and decrease of GSH, CAT, GPx, and SOD by GEN administration. Co-administration with GA showed reduction in the levels of MDA, NO, Cr, and BUN and increase in GSH, CAT, GPx, and SOD. Also, the nephroprotective effect of GA was confirmed by the histological examination of the kidneys. The results of our study showed that GA exerts a significant nephroprotective effect against GEN-induced nephrotoxicity.

Corrigendum to "Chitosan Prevents Gentamicin-Induced Nephrotoxicity via a Carbonyl Stress-Dependent Pathway".

[This corrects the article DOI: 10.1155/2015/675714.].

O-37 Preventing aminoglycoside-induced nephrotoxicity using statins: an example of bench-to-bedside research

Background Megalin-mediated endocytosis is the prin-cipal pathway for the accumulation of aminoglycosides in proximal tubule epithelial cells,1 resulting in kidney toxicity. Activation of this pathway depends on intermediates derived from mevalonate, the product of 3-hydroxy-3-meth-ylglutaryl-coenzyme A (HMG-CoA) reduction, catalysed by HMG-CoA reductase.2 We hypothesised that inhibition of HMG-CoA reductase by statins would reduce uptake of aminoglycosides in the proximal tubule, leading to a re-duction in toxicity. This has previously been demonstrated in vitro.3 We tested this in two in vivo models. Methods Sprague Dawley rats, (n=4/group) received in-traperitoneal (IP) dosing with saline (control), gentamicin (200 mg/kg/day), rosuvastatin (40 mg/kg/day), or gentami-cin and rosuvastatin for 9 days. Nephrotoxicity was measured using urinary N-Acetyl-β-d-glucosaminidase (NAG) and kidney injury molecule-1 (kim-1) on urine samples collected within 24 hours after the final dose. Male Hartley guinea pigs (n=6/group) received IP dosing with saline (control), gentamicin (100 mg/kg/day), statin, or combined gentami-cin and statin (simvastatin or rosuvastatin, 0.4 to 40 mg/kg/day) for 9 days. Nephrotoxicity was measured using serum creatinine and blood urea nitrogen (BUN) on urine samples collected within 24 hours after the final dose. Results In rats co-administered rosuvastatin and gentami-cin, urinary concentrations of NAG and kim-1 were signifi-cantly lower than for gentamicin alone (p Conclusion Rosuvastatin inhibits gentamicin-induced nephrotoxicity in both rat and guinea pig models; in the latter, at therapeutic doses used in humans. This led to an RCT in children which has just completed recruitment. This bench-to-bedside translational research showcases the exciting area of drug repurposing with potential for signifi-cant patient benefit.

The Effect of Nigella Sativa Linn (Kalajira) Extract on Gentamicin- Induced Nephrotoxicity in Experimental Rats

The pathogenesis of gentamicin-induced nephrotoxicity has shown to generate oxygen free radicals. Several free radical scavengers are well recognized to ameliorate the nephrotoxicity. The seeds and oil of nigella sativa were reported to possess strong antioxidant properties and was effective against disease and chemically-induced hepatotoxicity and nephrotoxicity.The experiments were carried out in two parts, Experiment I and Experiment II, on a total of 35 rats of 8-12 weeks old and weighing between 200 and 230g. Nephrotoxicity and amelioration of nephrotoxicity was evaluated by measurement of concentrations of serum creatinine. The rats were induced nephrotoxicity by subcutaneous injection of gentamicin 100mg/kg/day for 9 days and were sacrificed on 10th day. The results indicated that gentamicin treatment caused marked renal tubular damage significant increase (P&lt;0.001) of serum creatinine concentrations when compared to those of control.When n-hexane extract of N.sativa was administered as low and high dose with gentamicin and compared with the gentamicin treated groups, it was found that in these two groups there was significant decrease (P&lt;0.001) of serum creatinine levels. When these two groups were compared with each other, it was observed that more amelioration occurred significantly in high dose treatment group than in the low dose treatment group. This study established that oral administration of n-hexane extract of N. sativa was able to produce considerable improvement from the nephrotoxic action of gentamicin in rats. The best amelioration was obtained in high dose treatment. Low dose treatment brought out the least amelioration of them all. Future works could better be directed towards obtaining the specific ingredient and the specific mechanism responsible for nephroprotection. We are hopeful that complete amelioration might not be impossible if given in proper doses or more effectively if we could extract the actual ingredients responsible for nephroprotection and can use them eventually.J Dhaka Medical College, Vol. 25, No.2, October, 2016, Page 119-123

Effects of Cobalamin (Vitamin B12) on Gentamicin Induced Nephrotoxicity in Rat.

Background The main side effect of gentamicin is nephrotoxicity. The effect of cobalamin (Cob) was investigated on gentamicin nephrotoxicity in rats. Methods Renal injury induced by i.p. injection of gentamicin (100 mg/kg) for 8 consecutive days. Cobalamin (6 mg/kg/day, i.p) treatment was done for 8 consecutive days as co-treatment and post-treatment protocol. Results Cobalamin significantly increased creatinine clearance levels and renal blood flow which were reduced by gentamicin. Also, cobalamin significantly improved serum electrolytes (sodium and potassium) levels which were disturbed by gentamicin. Cobalamin significantly compensated deficits in the antioxidant defense mechanisms, suppressed lipid per oxidation and ameliorated renal tissue damage mediated by gentamicin. Conclusion The results of the current study indicated that cobalamin effectively protected the kidney tissue against gentamicin induced acute nephrotoxicity in rats. The antioxidant and anti-inflammatory activities can be supposed the main factors responsible for the nephroprotective effect of cobalamin.

Clinico-Biochemical and Nephroprotective Effects of Medicinal Herbs on Gentamicin Induced Nephrotoxicity in Wistar Rats

Nephrotoxicity followed by kidney disease is the main complication of gentamicin treatment. Medicinal plants and herbs have played an important role in the prevention and treatment of kidney diseases. With this concern the ethanol extract of Zingiber officinale rhizomes , ethanol extract of Tinospora cordifolia roots and methanol extract of Cajanus indicus leaves were compared for their nephroprotective effect in the Wistar rats. A total of 48 Wistar rats were distributed into six equal groups (n=8) and were exposed to gentamicin sulphate @ 100 mg/kg orally for 7 days to induce nephrotoxicity in 5 groups. Group G1 was kept as healthy control and group G2 was considered as untreated induced nephrotoxic control, whereas the rats of groups G3, G4, G5 and G6 were given, along with gentamicin sulphate @ 100 mg/kg, extracts of Zingiber officinale @ 400 mg/kg b.wt, Tinospora cordifolia 200 mg/kg b.wt, Cajanus indicus @ 400 mg/kg b.wt and syrup Cystone @ 500 mg/kg b.wt., respectively, orally for 7 consecutive days as neproprotective drugs. A significant (P less than 0.05) increase was observed in the values of plasma BUN, creatinine, urea, ALP, GGT, uric acid, calcium and phosphorus, whereas the total protein and albumin were found significantly (P less than 0.05) decreased on day 7 in rats receiving gentamicin alone (G2). However, there was no significant alteration in the values of above mentioned parameters in rats of G1 (healthy control), G4 and G6, which remained within the normal physiological range, suggesting nephroprotective role of herbal extracts in rats.

Altered gene expression profile in a rat model of gentamicin-induced ototoxicity and nephrotoxicity, and the potential role of upregulated Ifi44 expression.

As demonstrated by Alport syndrome, the co-occurrence of auditory and urinary system malformations, and gentamicin-induced ototoxicity and nephrotoxicity, the ears and kidneys potentially share certain molecular pathways. In the present study, microarray chips were used to analyze the changes in the gene expression profile using a rat model of gentamicin-induced ototoxicity and nephrotoxicity, using rat liver tissue as a control. A number of genes were identified to exhibit similar expression changes in the rat ears and kidney tissues, among which microtubule-associated protein 44 (Ifi44), was selected for further analysis to validate its expression changes and confirm potential involvement in the inflammation process in the disease model. Ifi44 is a member of the type I interferon-inducible gene family. Reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry were performed; the results demonstrated that more inflammatory cells were present in cochlear and renal parenchyma in gentamycin-induced rats, and Ifi44 expression was increased in these two organs compared with control rats. Taken together, with its role in lupus nephritis and expression in the inner ear, the results suggested that Ifi44 is potentially involved in the inflammation associated with gentamicin-induced ototoxicity and nephrotoxicity. The approach of the current study has also provided a strategy for delineating common pathways shared by organs involved in specific diseases.

The effect of Vitis vinifera L. cv. Merlot seed extract on gentamicin-induced nephrotoxicity in broilers

The effect of Vitis vinifera L. cv. Merlot seed extract on gentamicin-induced nephrotoxicity in broilers