• YAKHAK HOEJI
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• v.36 no.6
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• pp.570-576
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• 1992

The treatment with gentamicin in the presence of pretreatment with bismuth nitrate significantly reduced blood urea nitrogen compared with given gentamicin alone. But the amelioration of gentamicin-induced nephrotoxicity by bismuth nitrate was abolished by pretreatment with indomethacin that is cyclooxygenase inhibitor, which significantly decreased renal glutathione S-transferase activity and thiobarbituric acid reactive substance compared with mice of given gentamicin and bismuth nitrate. On the other hand, treatment with bismuth nitrate significantly increased prostaglandin $E_2$ production in rat kidney slice. These results suggest that bismuth nitrate might ameliorate the nephrotoxicity of gentamicin via prostaglandin $E_2$ production.

• Toxicological Research
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• v.29 no.1
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• pp.61-67
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• 2013

Development of a therapy providing protection from, or reversing gentamicin-sulfate (GS)-induced oxidative stress and nephrotoxicity would be of great clinical significance. The present study was designed to investigate the protective effects of Houttuynia cordata Thunb. (HC) against gentamicin sulfate-induced renal damage in rats. Twenty-eight Sprague-Dawley rats were divided into 4 equal groups as follows: group 1, control; group 2, GS 100 mg/kg/d, intraperitoneal (i.p.) injection; group 3, GS 100 mg/kg/d, i.p. + HC 500 mg/kg/d, oral; and group 4, GS 100 mg/kg/d i.p. + HC 1000 mg/kg/d, oral administration). Treatments were administered once daily for 12 d. After 12 d, biochemical and histopathological analyses were conducted to evaluate oxidative stress and renal nephrotoxicity. Serum levels of creatinine, malondialdehyde (MDA), and blood urea nitrogen (BUN), together with renal levels of MDA, glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were quantified to evaluate antioxidant activity. Animals treated with GS alone showed a significant increase in serum levels of creatinine, BUN, and MDA, with decreased renal levels of GSH, SOD, and CAT. Treatment of rats with HC showed significant improvement in renal function, presumably as a result of decreased biochemical indices and oxidative stress parameters associated with GS-induced nephrotoxicity. Histopathological examination of the rat kidneys confirmed these observations. Therefore, the novel natural antioxidant HC may protect against GSinduced nephrotoxicity and oxidative stress in rats.

• Journal of Oriental Physiology
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• v.14 no.2 s.20
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• pp.189-198
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• 1999

Aminoglycosides, including gentamicin, have been used as antibiotics for the various infections by gram-negative bacteria. However, there are some restrictions for using these drugs. Gentamicin, a typical aminoglycoside, has the side effect of nephrotoxicity, including polyuria, glycosuria, proteinuria, glomerulonephritis, and uremia. The aims of this study were to examine the prevention or reduction effects of Jinmootang on the gentamicin-induced nephrotoxicity and to investigate the possible mechanisms on the effect of Jinmootang. The subcutaneous injections of 60mg of gentamicin per kg of boby weight to Sprague-Dawley rats for 8 days induced typical symptoms of nephrotoxicity by aminoglycosides. 0.6ml of water extract Jinmootang (100ml/chup) was orally treated in the experimental animal. 24-hour urine was collected with the metabolic cage and plasma was sampled from the abdominal aorta. The plasma concentration of sodium was significantly decreased by the treatment of gentamicin but it was not-significantly changed by the treatment of Jinmootang to the animal. The concentration of potassium was greatly decreased in the gentamicin-treated animals. However. it was returned to the normal level in the Jinmootang-treated animals. The concentrations of creatinine and urea were increased by gentamicin treatment. But, Jinmootang reduced these concentrations. Nevertheless, the osmolalities of plasma in both group were not different from each other. Even though the plasma concentration of aldosterone was not significantly changed, the mean value was increased by the gentamicin intoxication. The concentration of aldosterone was decreased by the treatment of Jinmootang. The reduction of aldosterone level in plasma could be a factor to improve the hypokalemia. The fractional excretion of potassium was much higher than normal by the treatment of gentamicin and it was decreased by 50% in the Jinmootang-treated rats. Therefore, the reabsorption of potassium was significantly increased by the treatment of Jinmootang, even though the filtered load of potassium in the experimental group was much highter than control. Even though the concentration of plasma aldosterone was decreased by the treatment of Jinmootang, the fractional excretion of sodium was not increased, slightly lower. These data suggested that Na reabsorption was increased in the proximal tubule by Jinmootang. The filtered load of glucose in the Jinmootang-treated group was greater than in control. Nevertheless, the fractional excretion of glucose in the experimental group was not different from that in control. These results indicate that glucose reabsorption was increase in the proximal tubule by Jinmootang treatment. The results of this study suggest that Jinmootang could improve the some nephrotoxic symptoms induced by gentramicin treatment. Hypokalemia, the reduced glomerular filtration rate, and dysfunctions of renal proximal tubule and distal nephron were significantly recovered to normal level. The increase of glomerular filtration rate by Jinmootang might contribute to eliminate the waste product, including creatinine and urea, and/or gentamicin through the kidney.

• Journal of Veterinary Science
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• v.21 no.6
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• pp.81.1-81.10
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• 2020

Background: Although previous in vivo studies explored urinary microRNA (miRNA), there is no agreement on nephrotoxicity-specific miRNA biomarkers. Objectives: In this study, we assessed whether urinary miRNAs could be employed as biomarkers for nephrotoxicity. Methods: For this, literature-based candidate miRNAs were identified by reviewing the previous studies. Female Sprague-Dawley rats received subcutaneous injections of a single dose or repeated doses (3 consecutive days) of gentamicin (GEN; 137 or 412 mg/kg). The expression of miRNAs was analyzed by real-time reverse transcription-polymerase chain reaction in 16 h pooled urine from GEN-treated rats. Results: GEN-induced acute kidney injury was confirmed by the presence of tubular necrosis. We identified let-7g-5p, miR-21-3p, 26b-3p, 192-5p, and 378a-3p significantly upregulated in the urine of GEN-treated rats with the appearance of the necrosis in proximal tubules. Specifically, miR-26-3p, 192-5p, and 378a-3p with highly expressed levels in urine of rats with GEN-induced acute tubular injury were considered to have sensitivities comparable to clinical biomarkers, such as blood urea nitrogen, serum creatinine, and urinary kidney injury molecule protein. Conclusions: These results indicated the potential involvement of urinary miRNAs in chemical-induced nephrotoxicity, suggesting that certain miRNAs could serve as biomarkers for acute nephrotoxicity.

• Toxicological Research
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• v.7 no.1
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• pp.37-46
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• 1991

To evaluate the influence of ochratoxin A on the pharmarcokinetics of gentamicin, gentamicin concentrations in the serum, renal cortex and medulla together with parameters of the renal function and histological changes were compared between ochratoxin A-treated rats (0.1 mg of ochratoxin A/kg of body weight, ip, daily for 14 days) and normal rats. Gentamicin was given with a single intramuscular injection (10mg/kg of body weight). Ochratoxin A resulted in an increase of the half-life, the area under the concentration-time curve, the apparent volume of distribution and a decrease of the total body clearance of gentamicin, and accumulated significantly (p<0.01) more gentamicin in the kidneys.

• Molecular & Cellular Toxicology
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• v.2 no.3
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• pp.185-192
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• 2006

To elucidate the molecular mechanisms associated with early renal injury induced by gentamicin, the most commonly used antibiotics worldwide in the treatment of Gram-negative bacterial infections. We have identified genes differentially expressed at different duration of gentamicin administration. C57BL/6 female mice were treated daily with gentamicin (20 mg/kg, 100 mg/kg, and 200mg/kg) for 7 days and then sacrificed at day 1, 3, and 7 after administration. Standard blood biochemistry and histopathological observation indicative of nephrotoxicity were made. Total RNA was extracted from the kidney for microarray analysis using Affymetrix $GeneChip^{\circledR}$. Five hundred and seventy eight genes were identified as being either up-or down-regulated over 2-fold changes during early renal injury (p<0.05) and were analyzed by hierarchical clustering. The results showed that the genes involved in early immune responses were differentially regulated during early renal injury. Principal component analysis (PCA) confirmed sample separation according to the degree of renal toxicity. In addition, we identified two potential biomarkers that may predict early renal toxicity. This data may contribute to elucidate of the genetic events during early renal injury and to discover the potential biomarkers for nephrotoxicity induced by gentamicin.

• CELLMED
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• v.13 no.6
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• pp.5.1-5.8
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• 2023

Objectives: Cassia occidentalis L. is a weed belonging to the Caesalpiniaceae family. The root of this medicinal plant is used for the treatment of various ailments, including kidney diseases. The present study was aimed at evaluating the nephroprotective effects of HAE of the roots of Cassia occidentalis L. against gentamicininduced renal toxicity in albino Wistar rats. Methods: The renal toxicity was induced by subcutaneous administration of gentamicin at 100 mg/kg in the rats belonging to the disease control and treatment groups from the 4^th to the 8^th day. The rats in the treatment group received HAE of the roots of Cassia occidentalis L. at 67 mg/kg b. w. orally for 8 days, while no treatment was given to the rats in the disease control and plain control groups. At the end of the experiment, renal biomarkers viz; s. creatinine, b. urea, and s. uric acid, were investigated. The histopathological examination of the kidney specimens was also carried out. Results: The results of the present study revealed that renal function biomarkers such as s. creatinine, b. urea, and s. uric acid were significantly reduced in the rats of the treatment group as compared to those of the disease control group. Moreover, the histoarchitecture reports of the treatment group's kidney specimens showed significant improvements. Conclusion: The results suggested that the HAE of Cassia occidentalis L. roots promisingly prevented kidney injury in gentamicin-induced nephrotoxic rats. This effect might be due to improved clearance of gentamicin from the renal tubule and decreased generation of reactive oxygen species (ROS).

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.4
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• pp.403-411
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• 1997

To elucidate the mechanism of gentamicin induced renal dysfunction, renal functions and activities of various proximal tubular transport systems were studied in gentamicin-treated rats (Fisher 344). Gentamicin nephrotoxicity was induced by injecting gentamicin sulfate subcutaneously at a dose of 100 $mg/kg{\cdot}day$ for 7 days. The gentamicin injection resulted in a marked polyuria, hyposthenuria, proteinuria, glycosuria, aminoaciduria, phosphaturia, natriuresis, and kaliuresis, characteristics of aminoglycoside nephropathy. Such renal functional changes occurred in the face of reduced GFR, thus tubular transport functions appeared to be impaired. The polyuria and hyposthenuria were partly associated with a mild osmotic diuresis, but mostly attributed to a reduction in free water reabsorption. In renal cortical brush-border membrane vesicles isolated from gentamicin-treated rats, the $Na^+$ gradient dependent transport of glucose, alanine, phosphate and succinate was significantly attenuated with no changes in $Na^+-independent$ transport and the membrane permeability to $Na^+$. These results indicate that gentamicin treatment induces a defect in free water reabsorption in the distal nephron and impairs various $Na^+-cotransport$ systems in the proximal tubular brush-border membranes, leading to polyuria, hyposthenuria, and increased urinary excretion of $Na^+$ and other solutes.

• Korean Journal of Veterinary Research
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• v.26 no.1
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• pp.125-137
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• 1986

Sprague-Dawley rats received subcutaneous injections of gentamicin sulfate, 50 and 100mg/kg for 3, 7 and 10 days. The hematological and blood chemical values were determined. Kidneys were examined histologically and ultrastructurally. The results obtained were summarized as follows; 1. The serum values of aspartate transaminase, blood urea nitrogen and creatinine in the rats administered gentamicin, 50 and 100mg/kg/day were significantly increased than those in the control. 2. The ratio of kidney weight to body weight was significantly increased in the rats injected gentamicin, 100mg/kg for 10 days than those in the control. 3. The brush borders of proximal convoluted tubules in the kindneys received gentamicin, 50 and 100mg/kg/day were decreased or absent in periodic acid-Schiff staining. 4. The necrosis of proximal convoluted tubules was shown in the rats given gentamicin, 50 and 100mg/kg for 7 and 10 days. 5. The regeneration of the proximal tubular epithelia was observed in the rats treated gentamicin, 100mg/kg for 10 days. 6. The number and size of lysosomes were increased in the proximal convoluted tubules of the rats injected gentamicin, 50mg/kg for 7 days, many of which contained myeloid bodies.

• Molecular & Cellular Toxicology
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• v.3 no.1
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• pp.60-67
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• 2007

Gentamicin is a broad-spectrum aminoglycoside antibiotic used in the treatment of bacterial infection. Although side effects of gentamicin such as nephrotoxicity and ototoxicity have been investigated, the information on the hepatic effects of gentamicin is still limited. In the present study, gene expression profiles were analyzed in the liver of gentamicin treated mice using Affymetrix GeneChip$^{(R)}$ Mouse Expression 430A 2.0 Array. Totally, 400 genes were identified as being either up- or down-regulated over 1.5-fold changes (P<0.01) in the liver of gentamicin treated mice. Among these deregulated genes, 16 up-regulated genes mainly involved in transport (Kif5b, Pex14, Rab14, Clcn3, and Necap1) and 20 down-regulated genes involved in lipid and other metabolisms (Hdlbp, Gm2a, Uroc1, and Dak) were selected using k-means clustering algorithm. The functional classification of differentially expressed genes represented that several stress-related genes were regulated in the liver by gentamicin treatment. This data may contribute in understanding the molecular mechanism in the liver of gentamicin treated mice.