IPSIndian Journal of Pharmacology
Home  IPS  Feedback Subscribe Top cited articles Login 
Users Online : 15377 
Small font sizeDefault font sizeIncrease font size
Navigate Here
  Search
 
  
Resource Links
 »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
 »  Article in PDF (1,263 KB)
 »  Citation Manager
 »  Access Statistics
 »  Reader Comments
 »  Email Alert *
 »  Add to My List *
* Registration required (free)

 
In This Article
 »  Abstract
 » Introduction
 »  Materials and Me...
 » Results
 » Discussion
 »  References
 »  Article Figures
 »  Article Tables

 Article Access Statistics
    Viewed4137    
    Printed138    
    Emailed3    
    PDF Downloaded254    
    Comments [Add]    
    Cited by others 6    

Recommend this journal

 


 
 Table of Contents    
RESEARCH ARTICLE
Year : 2014  |  Volume : 46  |  Issue : 6  |  Page : 608-612
 

Protective effect of L-arginine on gentamicin-induced nephrotoxicity in rats


1 Mersin University Medical Faculty Department of Medical Education, 33343 Yenisehir, Mersin, Turkey
2 Department of Pharmacology, Çukurova University Medical School, 01330, Balcali, Adana, Turkey

Date of Submission06-Jan-2014
Date of Decision18-Jan-2014
Date of Acceptance27-Jul-2014
Date of Web Publication18-Nov-2014

Correspondence Address:
lbrahim Bashan
Mersin University Medical Faculty Department of Medical Education, 33343 Yenisehir, Mersin
Turkey
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7613.144915

Rights and Permissions

 » Abstract 

Introduction: L-arginine has a protective effect on gentamicin-induced renal failure and it may decrease the tubular reabsorption of another cationic substance, gentamicin due to its cationic structure. The aim of this study is to compare the possible protective effects of L-arginine and its inactive isomer D-arginine on gentamicin-induced nephrotoxicity in rats.
Materials and Methods: Wistar albino rats were housed in metabolic cages and assigned to six groups as: control group, gentamicin (100 mg/kg), gentamicin + L-arginine (2 g/l), gentamicin + D-arginine (2 g/l), gentamicin + L-arginine + Nv-nitro-L-arginine methyl ester (L-NAME) (100 mg/l) and gentamicin + D-arginine + L-NAME. Gentamicin was administered by subcutaneous injections and the other drugs were added in drinking water for seven consecutive days. The animals were killed by decapitation and intracardiac blood and urine samples were obtained on the seventh day. Blood urea nitrogen, serum creatinine, sodium, potassium, urine gamma glutamyl transferase, creatinine, sodium, potassium and gentamicin levels were measured using High Performance Liquid Chromatography (HPLC) technique.
Results: Gentamicin treated group had significant increase in blood urea nitrogen, serum creatinine, fractional Na excretion and urine gamma glutamyl transferase levels, and significant decrease in creatinine clearance compared to the control group. L-arginine and D-arginine reversed these findings. L-NAME abolished the nephroprotective effect of L-arginine. The urinary levels of gentamicin were significantly increased in rats treated with L-arginine or D-arginine compared to those treated with gentamicin. L-arginine and D-arginine reversed the advanced degenerative changes due to gentamicin administration in histopathological examination.
Conclusion: Our study revealed the protective effect of L-arginine on gentamicin-induced nephrotoxicity, the contribution of the cationic feature of L-arginine, and the major role of NO in this protective effect.


Keywords: D-arginine, gentamicin, HPLC, L-arginine, nephrotoxicity


How to cite this article:
Bashan l, Bashan P, Secilmis MA, Singirik E. Protective effect of L-arginine on gentamicin-induced nephrotoxicity in rats . Indian J Pharmacol 2014;46:608-12

How to cite this URL:
Bashan l, Bashan P, Secilmis MA, Singirik E. Protective effect of L-arginine on gentamicin-induced nephrotoxicity in rats . Indian J Pharmacol [serial online] 2014 [cited 2023 Sep 22];46:608-12. Available from: https://www.ijp-online.com/text.asp?2014/46/6/608/144915



 » Introduction Top


Aminoglycoside antibiotics are the most commonly used worldwide in the treatment of gram (-)negative bacterial infections. However, aminoglycosides induce nephrotoxicity in observed 10-20% of therapeutic courses. [1] The widespread therapeutic use of the gentamicin is limited because of its nephrotoxic side effect and oxidative damage which can lead to acute renal failure. [1],[2],[3]

Although the mechanism underlying gentamicin-induced renal cellular damage has not been entirely elucidated, generation of superoxide anion, hydrogen peroxide (H 2 O 2 ) and hydroxyl radicals has been attributed to its deleterious effect on the kidney. [4],[5] An association between nephrotoxicity and oxidative stress has been confirmed in many experimental models. [6],[7] The possible involvement of the L-arginine-Nitric oxide (NO) pathway in gentamicin-induced nephrotoxicity has been suggested by Rivas-Cabanero et al. These investigators reported increased glomerular synthesis of NO in rats with gentamicin-induced renal failure. [8]

Arginine, an essential amino acid, has a positively charged guanidine group. Arginine is well-designed to bind the phosphate anion, and is often found in the active centers of proteins that bind phosphorylated substrates. As a cation, arginine plays an important role in maintaining the overall charge balance of a protein. L-Arginine has been intensively investigated, mainly since it is a precursor of NO that is a highly reactive and multifunctional molecule involved in many physiological processes, such as cardiovascular system, nervous system and immunological reactions. [9] On the other hand, D-arginine is frequently used in studies on L-arginine/NO pathway is an inactive form of L-arginine, because the D-enantiomer is not a substrate for the stereospecific NO synthase. [10],[11],[12],[13],[14]

Data from recent studies showed that the cationic proteins and peptides, inhibit the uptake of a nephrotoxic drug, gentamicin, which is highly accumulated in the kidneys. [15],[16] Some authors report that L-arginine might have protected tubular function simply by decreasing gentamicin reabsorption in the proximal tubules. [17]

It is known that gentamicin has an organic polycationic structure. L-arginine consists of a functional cationic group of guanidin and due this cationic structural trait it can reduce gentamicin tubular reabsorption and increase gentamicin urinary excretion via competition. Therefore, in the present study, we aimed to investigate the possible protective effects other than NO synthesis of L-arginine and its inactive isomere D-arginine on gentamicin-induced nephrotoxicity in rats due to their structural similarities using High Performance Liquid Chromatography (HPLC) technique.


 » Materials and Methods Top


Experimental Animals

In this study, 42 male Wistar albino rats (appoximately 250-300 g weight) were procured from the Medical Science Experimental Research Center at Cukurova University. Rats were sheltered in metabolic cages at room temperature (24 ± 2°C) under 12 hours daylight, 12 hours dark conditions. The study was approved by the Medical Science Experimental Research Center Ethics Committee.

Experimental Protocol

The rats were divided into six groups and each group consisted of seven rats. The groups were as follows:

  • Group 1(Control group): This group was treated with normal food and tap water
  • Group 2(Gentamicin Group): This group was treated with (100 mg/kg gentamicin) subcutaneous (s.c.) injection for seven days
  • Group 3(Gentamicin + L-arginine Group): This group was treated with gentamicin injection and L-arginine (2 g/l) was added to their drinking water
  • Group 4(Gentamicin + D- arginine Group): This group was treated with gentamicin injection and D-arginine (2 g/l) was added to their drinking water
  • Group 5(Gentamicin + L-arginine + L-NAME Group): This group was treated with gentamicin injection and L-arginine (2 g/l) and L-NAME (100 mg/l) were added to their drinking water
  • Group 6 (Gentamicin + D-arginine + L- NAME Group): This group was treated with gentamicin injection and D-arginine (2 g/l) and L-NAME (100 mg/l) was added to in their drinking water.


During seven days water intake and urine volume were followed.

After the gentamicin injection, urine samples were collected on the first (initial), fourth (middle) and eighth day (final) to compare gentamicin levels. Ketamine (40 mg/kg) was given for anesthesia 24 hours after the final injection and intracardiac blood was obtained and animals were killed by decapitation. Providing the aseptic conditions, left kidney was removed by middle abdominal line incision for histopathological examination.

Biochemical Analysis

Blood urea nitrogen (BUN), serum creatinine, sodium (Na + ), potassium (K + ) levels were investigated from the blood of experimental animals. In addition, gama glutamyl transferase (GGT), creatinine, Na + K + levels in their urine were measured at Central Laboratory of Cukurova University. The clearance of creatinine (C Cr ) and fractional Na excretion (FE Na ) were calculated using the standard methods as below.



Histopathology of Kidney

The kidneys were treated with paraffine after the formaline (10% solution) fixation and approximately 3-5 μm cross-sections were dyed with hematoxylin-eosin. Tubular necrosis, degenerative variations and tubular regeneration were found under fluorescence microscope.

Measurement of Gentamicin Levels

Gentamicin levels of urine samples were evaluated according to the Kafkas et al., (2008) with major modifications. [18] The samples were stored at −20 o C until analysis. HPLC analysis was performed in the Subtropical Fruits Research and Experimental Center Laboratory of Cukurova University. Identification and quantification were conducted using gentamicin (Sigma) standards. HPLC technique was used to identification and quantification of urine gentamicin levels.

Fort this purpose, Hewlett Packard 1100 series, HP-1100 UW dedector (210 nm) and Zorbax SB-C18 (10 cm × 4.6 mm, 1.8 μm, Beckman) column were used and flow speed was applied 1 ml/min.

Statistical analysis

Data was presented as means ± Standard error of mean (S.E.M) for the groups. A one-way variance analysis (One-Way ANOVA) method was used for comparison of results. Comparison of groups were performed using Bonferroni test. The level of significance was set as P < 0.05.

Experimental Drugs

In this study, L-Arginine monohydrochloride, N-nitro-L-arginine methyl ester monohydrochloride, D-Arginine monohydrochloride were procured from Sigma whereas gentamicin sulphate was procured from Schering-Plough.


 » Results Top


Control Group

The results of the blood and urine samples on the eighth day were found normally [Figure 1], [Figure 2], [Figure 3], [Figure 4] and [Table 1]. The renal particles and kidney tubules with normal structure were seen in the histopathological examination of the kidney tissues (data not shown).
Table 1: Plasma Na+, plasma K+ and urine GGT (gama glutamyl transferase) values of the groups. Data are expressed as means±S.E.M. for the groups; n=7 in each group. Statistical analysis was performed by one-way analysis of variance (ANOVA) and comparison of groups were performed using Bonferroni test


Click here to view
Figure 1: The comparison of blood urea nitrogen levels of the groups. Data are expressed as means ± S.E.M. for the groups; n = 7 in each group. Statistical analysis was performed by one-way analysis of variance (ANOVA) and comparison of groups were performed using Bonferroni test. *(P < 0.05) vs control group, +(P < 0.05) vs gentamicin group

Click here to view
Figure 2: The comparison of serum creatinine levels of the groups. Data are expressed asmeans ± S.E.M. for the groups; n = 7 in each group. Statistical analysis was performed by one-way analysis of variance (ANOVA) and comparison of groups were performed using Bonferroni test. *(P < 0.05) vs control group, +(P < 0.05) vs gentamicin group

Click here to view
Figure 3: The comparison of FENa % (fractional Na excreation) levels of the groups. Data are expressed as means ± S.E.M. for the groups; n = 7 in each group. Statistical analysis was performed by one-way analysis of variance (ANOVA) and comparison of groups were performed using Bonferroni test. *(P < 0.05) vs control group, +(P < 0.05) vs gentamicin group

Click here to view
Figure 4: The comparison of Ccr (creatinine clearance) values of the groups. Data are expressed as means ± S.E.M. for the groups; n = 7 in each group. Statistical analysis was performed by one-way analysis of variance (ANOVA) and comparison of groups were performed using Bonferroni test. *(P < 0.05) vs control group, +(P < 0.05) vs gentamicin group

Click here to view


Gentamicin Group

Serum creatinine, BUN, FE Na and urine GGT levels increased significantly after 8 days of gentamicin administration compared to the controls P < 0.05 [Figure 1], [Figure 2], [Figure 3] and [Table 1]. This group was also characterized by a significantly lower creatinine clearance. However, there is no significant differences in other parameters. Degenerative changes were observed in the epitelial tissue of tubular epithelial tissue in the group treated with gentamicin. The epithelial cells covering the tubulus showed an increased acidophilic epithelial cell cytoplasm and nuclei couldn't be identified, epithelial cells spilled renal particles abnormal capsular space was determined and also became narrow in some sites. The results of urine gentamicin levels were detected as shown in [Figure 5].
Figure 5: The comparison of urine gentamicin levels of Gentamicin, Gentamicin+L-arginine and Gentamicin+D-arginine applied groups. Data are expressed as means ± S.E.M. for the groups; n = 7 in each group. Statistical analysis was performed by one-way analysis of variance (ANOVA) and comparison of groups were performed using Bonferroni test. *(P < 0.05) vs gentamicin first group, +(P < 0.05) vs gentamicin in middle, and (P < 0.05) vs gentamicin in last group

Click here to view


Gentamicin + L-arginine Group

L-arginine administration provided marked protection manifested as significantly decreased serum creatinine, BUN, FE Na and urine GGT levels and significantly increased creatinine clearance compared to the gentamicin group P < 0.05 [Figure 1], [Figure 2], [Figure 3], [Figure 4] and [Table 1]. However, other parameters detected were insignificant.

In this group, renal particles were observed as normal structure, the fallen of tubular epithelium and slight grade degenerative changes were also detected. The group which was applied only gentamicin was compared with the group gentamicin with L-argininine; the urine gentamicine levels were increased and this enhancement found to be statistically significant [Figure 5].

Gentamicin + D-arginine Group

Compared to the gentamicin group, D-arginine administration significantly decreased serum creatinine, BUN, FE Na and urine GGT levels and significantly increased creatinine clearance P < 0.05 [Figure 1], [Figure 2], [Figure 3], [Figure 4] and [Table 1]. Besides this, other parameters detected were insignificant. In histopathological evaluation, slight grade degenerative changes and intracellular edema, necrosis and intermediate dropping were observed in tubular epithelium, as well.

The group which was applied only gentamicin was compared with the group gentamicin with D-arginine; the urine gentamicin levels were increased significantly [Figure 5].

Gentamicin + L-arginine + L-NAME Group

Comparison of gentamicin group, BUN levels increased significantly while other parameters were not found statistically significant [Figure 1], [Figure 2], [Figure 3], [Figure 4] and [Table 1]. According to the histopathological evaluation, enlargement of the renal corpuscle space, disappearance of cell details were observed, as well as fallen epithelium and advanced grade structural alternation were observed. As for the comparison with only gentamicin-applied to be group, the levels of gentamicin in urine were not significant [Table 2].
Table 2: The urine gentamicin levels of experimental groups. Data are expressed as means±S.E.M. for the groups; n=7 in each group. Statistical analysis was performed by one-way analysis of variance (ANOVA) and comparison of groups were performed using Bonferroni test

Click here to view


Gentamicin + D-arginine + L-NAME Group

Compared with the gentamicin group, BUN, serum creatinine, FE Na , C Cr , urine GGT, plasma Na + and plasma K + values were not significant [Figure 1], [Figure 2], [Figure 3], [Figure 4] and [Table 1]. According to the histopathological evaulation, deformation observed in kidney tissue and tubular necrosis was high. Among the urine samples, compared with the only gentamicin applied group, gentamicin levels were not significant [Table 2].


 » Discussion Top


The aim of the present study was to investigate the possible protective effects of L-arginine and its inactive isomere D-arginine on gentamicin-induced nephrotoxicity in rats due to their structural similarities.

Aminoglycosides are totally eliminated by glomerular filtration and reabsorbed by the proximal tubules. Even therapeutic doses of these antibiotics commonly lead to proximal tubular cell necrosis in humans. This pathology was known due to the accumulation of gentamicin in renal cortex. [19],[20] Similar results were obtained in this study and identification of nephrotoxicity criterias were found to be similar. The administration of gentamicin in rats induced a reduction in glomerular filtration rate as shown by a reduced creatinine clearance and increased serum creatinine. This impairment in glomerular function was accompanied by increased fractional excretion of Na + . This indicates proximal tubular dysfunction. The presence of tubular damage was further confirmed by the increased urinary excretion of the GGT and it indicates direct toxic injury. These findings correlated well with the renal morphological examination, which revealed tubular necrosis.

In rats treated with gentamicin and L-arginine together; biochemical and histopathological changes were found to be reversed. These results are similar to the previous reports. [21],[22] However, L-arginine diminished the acute tubular necrosis as well. This effect can be due to the other mechanisms in addition to L-arginine-NO pathway. L-arginine is known as precursor of NO and can be used for nitric oxide synthesis. This amino acid is present and synthesized as endogenous. This includes cationic two functional guanidine groups. [23] This aminoacid can inhibit tubular reabsorbtion similar to gentamicin which has a cationic character. According to this information, L-Arginine increases the gentamicin excretion in urine. For this purpose, in this study we aimed to identify and quantify gentamicin levels after the injection of gentamicin first day (first), fourth day (middle) and eighth day (last) in urine samples by HPLC technique. As for the L-arginine given groups; urine gentamicin levels were increased statistically compared to only gentamicin given group. This result supports our hypothesis that L-arginin might have protected tubular function simply by decreasing gentamicin reabsorption. But, this increase can be explained as the increase of NO production which is known as a strong vasodilator and this can provide the improvement of hemodynamics. On the other hand, D-arginine has a similar and cationic structure but does not play a role in NO synthesis. We also detected an increase in urine gentamicin levels in D-arginine group. This result showed that the nephroprotective effect of D-arginine also can be explained as cationic characteristic.

The effect of nitric oxide synthase inhibition on renal failure has been investigated. Recent datas provided evidence that endothelial NOS leads to restoration of renal function after injury, while activation of inducible NOS, leading to excessive NO production, causes tubular cytotoxicity and aggravates renal failure. In our study, nephroprotective effects of L-arginine are reversed by L-NAME which is a non-selective inhibitor. It causes tubular deformation by inhibition of eNOS while positive effects of NOS inhibition may be prevented. This result shows that, NO has a major important role on protective effect of L-arginine. Nitric oxide is the most important paracrine modulator and mediator of controlling of renal functions such as renal blood flow, renal autoregulation, glomerular filtration, renin excretion and Na excretion. Nitric oxide plays an important role in diabetic nephropathy, inflammatory glomerular abnormality, acute and chronic kidney failure, effects of nephrotoxicity of medicine and several kidney defective states. [24],[25]

In conclusion, the results of the present study demonstrate that administration of L-arginine and D-arginine has beneficial effects in rats with gentamicin-induced renal failure and that these effects are reversed by the NO-synthase inhibitor L-NAME. In addition, administration of L-arginine and its inactive form, D-arginine increases urine gentamicin levels. Althought it is known that NO has a major role on this protective effect, in our study L-arginine has also protected tubular function simply by decreasing gentamicin reabsorption in the proximal tubules due to having cationic structure. This protective mechanism other than NO synthesis can further be investigated.

 
 » References Top

1.
Balakumar P, Rohilla A, Thangathirupathi A. Gentamicin-induced nephrotoxicity: Do we have a promising therapeutic approach to blunt it? Pharmacol Res 2010;62:179-86.  Back to cited text no. 1
    
2.
Martinez-Salgado C, Lopez-Hernandez FJ, Lopez-Novoa JM. Glomerular nephrotoxicity of aminoglycosides. Toxicol Appl Pharmacol 2007;223:86-98.  Back to cited text no. 2
    
3.
Stojiljkovic N, Mihailovic D, Veljkovic S, Stoiljkovic M, Jovanovic I. Glomerular basement membrane alterations induced by gentamicin administration in rats. Exp Toxicol Pathol 2008;60:69-75.  Back to cited text no. 3
    
4.
Baliga R, Ueda N, Walker PD, Shah SV. Oxidant mechanisms in toxic acute renal failure. Am J Kidney Dis 1997;29:465-77.  Back to cited text no. 4
    
5.
Walker PD, Barri Y, Shah SV. Oxidant mechanisms in gentamicin nephrotoxicity. Ren Fail 1999;21:433-42.  Back to cited text no. 5
    
6.
Ghaznavi R, Faghihi M, Kadkhodaee M, Shams S, Khastar H. Effects of nitric oxide on gentamicin toxicity in isolated perfused rat kidneys. J Nephrol 2005;18:548-52.  Back to cited text no. 6
    
7.
Ozbek E, Turkoz Y, Sahna E, Ozugurlu F, Mizrak B, Ozbek M. Melatonin administration prevents the nephrotoxicity induced by gentamicin. BJU Int 2000;85:742-6.  Back to cited text no. 7
    
8.
Rivas-Cabanero L, Montero A, Lopez-Novoa JM. Increased glomerular nitric oxide synthesis in gentamicin-induced renal failure. Eur J Pharmacol 1994;270:119-21.  Back to cited text no. 8
    
9.
Saavedra-Molina A, Pina E. Stimulation of L-ornithine uptake and L-citrulline and urea biosynthesis by D-arginine. Biochem Int 1991;24:349-57.  Back to cited text no. 9
    
10.
Noda Y, Yamada K, Furukawa H, Nabeshima T. Involvement of nitric oxide in phencyclidine-induced hyperlocomotion in mice. Eur J Pharmacol 1995;286:291-7.  Back to cited text no. 10
    
11.
Calver A, Collier J, Vallance P. Dilator actions of arginine in human peripheral vasculature. Clin Sci (Lond) 1991;81:695-700.  Back to cited text no. 11
    
12.
Sander M, Chavoshan B, Victor RG. A large blood pressure-raising effect of nitric oxide synthase inhibition in humans. Hypertension 1999;33:937-42.  Back to cited text no. 12
    
13.
Chambers DC, Ayres JG. Effect of nebulised L- and D-arginine on exhaled nitric oxide in steroid naive asthma. Thora×2001;56:602-6.  Back to cited text no. 13
    
14.
McVeigh GE, Allen PB, Morgan DR, Hanratty CG, Silke B. Nitric oxide modulation of blood vessel tone identifed by arterial waveform analysis. Clin Sci (Lond) 2001;100:387-93.  Back to cited text no. 14
    
15.
Nagai J, Komeda T, Yumoto R, Takano M. Effect of protamine on the accumulation of gentamicin in opossum kidney epithelial cells. J Pharm Pharmacol 2013;65:441-6.  Back to cited text no. 15
    
16.
Nagai J, Komeda T, Katagiri Y, Yumoto R, Takano M. Characterization of protamine uptake by opossum kidney epithelial cells. Biol Pharm Bull 2013;36:1942-9.  Back to cited text no. 16
    
17.
Can C, Sen S, Boztok N, Tuglular I. Protective effect of oral L-arginine administration on gentamicin-induced renal failure in rats. Eur J Pharmacol 2000;390:327-34.  Back to cited text no. 17
    
18.
Kafkas E, Ozgen M, Ozogul Y, Türemis N. Phytochemical and fatty acid profile of selected red raspberry cultivars: A comparative study. J Food Qual 2008;1:67-78.  Back to cited text no. 18
    
19.
Mingeot-Leclercq MP, Tulkens PM. Aminoglycosides: Nephrotoxicity. Antimicrob Agents Chemother 1999;43:1003-12.  Back to cited text no. 19
    
20.
Zaske DE. Aminoglycosides. In: Ewans WE, Schentag JJ, Jusko WJ, editors. Applied Pharmocokinetics. Principles of Therapeutic Drug Monitoring. 3 rd ed. Vancouver: WA; 1992. p. 141-7.  Back to cited text no. 20
    
21.
Karatas Y, Secilmis MA, Karayaylalý Ý, Doran F, Buyukafsar K, Singirik E, et al . Effect of tempol (4-hydroxy tempo) on gentamicin-induced nephrotoxicity in rats. Fundam Clin Pharmacol 2004;18:79-83.  Back to cited text no. 21
    
22.
Secilmis MA, Karatas Y, Yorulmaz O, Buyukafsar K, Singirik E, Doran F, et al. Protective effect of L-arginine intake on the impaired renal vascular responses in the gentamicin-treated rats. Nephron Physiol 2005;100:p13-20.  Back to cited text no. 22
    
23.
Balsam L, Nikbakht N. L-Arginine inhibits vasopressin-stimulated mesangial cell Ca 2+ . Am J Physiol 1998;275:C352-7.  Back to cited text no. 23
    
24.
Matsamura Y, Nishiura M, Deuchi S, Hashimato N, Ogawa T, Seo R. Protective effect of FK409, a spontenous nitric oxide releaser, on ischemic acute renal failure in rats. J Pharmacol Exp Ther 1998;287:1084-91.  Back to cited text no. 24
    
25.
Noiri E, Peresieni T, Miller F, Goligorsky MS. In vivo targeting of inducible NO synthase with oligodeoxynucleotides protects rat kidney against ischemia. J Clin Invest 1996;97:2377-83.  Back to cited text no. 25
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]

This article has been cited by
1 Flavonoid-rich extract from Cittrulus lanatus (Watermelon) seed attenuated Ethanol-Induced Kidney injury in Wistar Rats
Sebastine Anthony Bazabang, Wusa Makena, Onyinoyi Bethel Onimisi, Hadiza Bello Rilwan, Hasiya Sule Buba, Victor Kayode Jerome, Ayuba Yohana
Pharmacological Research - Modern Chinese Medicine. 2023; : 100236
[Pubmed] | [DOI]
2 Evaluation of Nephroprotective Effect of Vortioxetine in Gentamicin-Induced Renotoxicity in Wistar rats
Meghana Bhat M., Vinutha R Bhat, Amrita Parida, Sushma R K, Basavaraj Poojar, Manju V.
Research Journal of Pharmacy and Technology. 2023; : 2223
[Pubmed] | [DOI]
3 Therapeutic role of nitroglycerin against copper-nitrilotriacetate induced hepatic and renal damage
Ayesha Rahman Ahmed, Senty Vun-Sang, Mohammad Iqbal
Human & Experimental Toxicology. 2022; 41: 0960327122
[Pubmed] | [DOI]
4 Comparison of the anti-inflammatory effects of different polar ginsenosides on rheumatoid arthritis
Jing Feng, Yuan Yu, Linmeng Song, Ruoyu Zhang, Yuqing Cao, Xue Du, Feiyan Tao, Hanyi Gao, Peng Xue
Industrial Crops and Products. 2022; 181: 114845
[Pubmed] | [DOI]
5 Renoprotective effect of Capsicum annum against ethanol-induced oxidative stress and renal apoptosis
Moumita Das, Subhashree Basu, Bhaswati Banerjee, Kuladip Jana, Anurupa Sen, Gouriprosad Datta
Journal of Food Biochemistry. 2021; 45(3)
[Pubmed] | [DOI]
6 Genome-Scale Model-Based Identification of Metabolite Indicators for Early Detection of Kidney Toxicity
Venkat R Pannala, Kalyan C Vinnakota, Shanea K Estes, Irina Trenary, Tracy P O'Brien, Richard L Printz, Jason A Papin, Jaques Reifman, Tatsuya Oyama, Masakazu Shiota, Jamey D Young, Anders Wallqvist
Toxicological Sciences. 2020; 173(2): 293
[Pubmed] | [DOI]



 

Top
Print this article  Email this article
 

    

Site Map | Home | Contact Us | Feedback | Copyright and Disclaimer | Privacy Notice
Online since 20th July '04
Published by Wolters Kluwer - Medknow