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 Table of Contents  
LETTER TO EDITOR
Year : 2019  |  Volume : 10  |  Issue : 1  |  Page : 123

The protective role of silymarin and aerobic exercise on gentamicin-induced nephrotoxicity


1 Water and Electrolytes Research Center, Department of Physiology, Isfahan University of Medical Sciences;Department of Physical Education and Sport Sciences, University of Isfahan, Isfahan, Iran
2 Department of Physical Education and Sport Sciences, University of Isfahan, Isfahan, Iran
3 Water and Electrolytes Research Center, Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran

Date of Submission28-Nov-2017
Date of Acceptance28-Nov-2017
Date of Web Publication05-Jul-2019

Correspondence Address:
Mehdi Nematbakhsh
Department of Physiology, Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpvm.IJPVM_522_17

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How to cite this article:
Alavijeh FS, Marandi SM, Talebi A, Nematbakhsh M. The protective role of silymarin and aerobic exercise on gentamicin-induced nephrotoxicity. Int J Prev Med 2019;10:123

How to cite this URL:
Alavijeh FS, Marandi SM, Talebi A, Nematbakhsh M. The protective role of silymarin and aerobic exercise on gentamicin-induced nephrotoxicity. Int J Prev Med [serial online] 2019 [cited 2019 Nov 20];10:123. Available from: http://www.ijpvmjournal.net/text.asp?2019/10/1/123/262212



Dear Editor,

Gentamicin (GM) is commonly used against Gram-negative microorganisms, but the compound's therapeutic use is mainly limited by nephrotoxicity which is observed in 10%–20% of patients treated with GM.[1] Silymarin (SM) as an antioxidant agent has anti-inflammatory actions, and it improves structural and enzymatic changes induced by GM.[2] On the other hand, lifelong physical activity has been recommended to improve antioxidant content.[3] Thirty-seven adult male Wistar rats (175.56 ± 2.24 g) were used in five groups as follows:

Group 1 (n = 6, control group) that received vehicle dimethyl sulfoxide (DMSO) for 3 days a week during the 6 week study period and then saline was injected for 10 days. Group 2 (n = 6, GM group) that received the same regimen as Group 1 but GM (100 mg/kg/day) for 10 days instead of saline. Group 3 (n = 7, GM + SM group) that received SM (200 mg/kg/day) dissolved in DMSO for 3 days a week during the 6 week study period and then GM was injected for 10 days. Group 4 (n = 9, GM + exercise [EX]) that received DMSO for 3 days a week and treadmill EX (5 days in week) during the 6 week study period and then GM was injected for 10 days. Group 5 (n = 9, GM + SM + EX) that received SM dissolved in DMSO for 3 days a week and EX during the 6 week study period and then GM was injected for 10 days.

The rats were exposed to treadmill EX 5 sessions a week for a period of 6 weeks as described before.[4],[5]

The levels of serum creatinine (Cr), blood urea nitrogen (BUN), nitrite (by Griess reaction), and malondialdehyde (MDA)[5],[6] were determined.

The removed kidney was weighted and subjected to hematoxylin and eosin staining. Kidney tissue damage score (KTDS) was graded from 0 to 4. Independent Student's t- test, Mann–Whitney test for comparison between control and GM groups, and ANOVA analysis followed by least significant difference, and Kruskal–Wallis tests were employed to compare the parameters between all GM-treated groups.

The serum levels of BUN (19.2 ± 1.0, 66.4 ± 11.6 mg/dl, P < 0.05) and Cr (0.48 ± 0.02, 1.16 ± 0.18 mg/dl, P < 0.05), KTDS (0.25 ± 0.25, 1.5 ± 0.22, P < 0.05), kidney weight (0.64 ± 0.01, 1.05 ± 0.12 g, P < 0.05), and body weight change (19.25 ± 2.92, −0.33 ± 3.46 g, P < 0.05) between control and GM alone treated groups were significant, while the serum level of MDA (4.37 ± 1.42, 4.72 ± 0.46 μmol/l) and nitrite (13.06 ± 1.01, 12.02 ± 0.51 μmol/l) were insignificant. In GM-treated groups, SM alone increased the serum levels of BUN and Cr as well as KTDS significantly (P < 0.05), but when SM was accompanied with EX or EX alone, decreased these parameters significantly (P < 0.05) [Figure 1]. The serum nitrite and MDA levels were 12.02 ± 0.51 and 4.72 ± 0.46, 15.67 ± 0.97 and 5.96 ± 0.62, 11.24 ± 0.85 and 6.77 ± 0.80, and 20.61 ± 5.03 μmol/l and 8.91 ± 1.88 μmol/l in Groups 2–5, respectively, with no significant difference between the groups.
Figure 1: The serum levels of blood urea nitrogen, creatinine, and kidney tissue damage score, kidney weight and change of body weight between the gentamicin-treated groups (see text for group information). * and # symbols indicate significant difference from gentamicin or gentamicin + silymarin groups, respectively (P < 0.05)

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SM exerts positive effects in patients with renal insufficiency.[6] Conversely, SM administration also resulted in persistence of oxidative stress and inflammatory processes, tubular necrosis, and apoptosis in rats with glycerol-induced acute kidney injury.[7] In our results, however, SM alone did not protect the kidney against GM, but aerobic EX either alone or accompanied with SM provides the protective effect against GM-induced nephrotoxicity. EX increased renal drug metabolism, and in agreement with our study, moderate EXs improve metabolic parameters, renal function, and structure on GM-induced acute kidney injury in rats.[8] As conclusion, aerobic EX alone or accompanied with SM may be recommended to attenuate GM-induced nephrotoxicity while SM as an antioxidant may not act such mission.

Acknowledgments

SM was provided by Goldaru Company (Esfahan, Iran) that is appreciated.

Financial support and sponsorship

This study was supported financially by Isfahan University of Medical Sciences.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ali BH. Agents ameliorating or augmenting experimental gentamicin nephrotoxicity: Some recent research. Food Chem Toxicol 2003;41:1447-52.  Back to cited text no. 1
    
2.
Mashayekhi M. Renoprotective effect of silymarin on gentamicin-induced nephropathy. Afr J Pharm Pharmacol 2012;6:2241-6.  Back to cited text no. 2
    
3.
Berzosa C, Cebrián I, Fuentes-Broto L, Gómez-Trullén E, Piedrafita E, Martínez-Ballarín E, et al. Acute exercise increases plasma total antioxidant status and antioxidant enzyme activities in untrained men. J Biomed Biotechnol 2011;2011:540458.  Back to cited text no. 3
    
4.
Ahmadi F, Nematbakhsh M, Kargarfard M, Eshraghi-Jazi F, Talebi A, Shirdavani S, et al. Effect of aerobic exercise against vanadyl sulphate-induced nephrotoxicity and hepatotoxicity in rats. J Renal Inj Prev 2016;5:183-7.  Back to cited text no. 4
    
5.
Zeynali F, Nematbakhsh M, Mojtahedi H, Poorshahnazari A, Talebi A, Pezeshki Z, et al. Protective role of aerobic exercise against cisplatin-induced nephrotoxicity in rats. Asian J Sports Med 2015;6:e24901.  Back to cited text no. 5
    
6.
Roozbeh J, Shahriyari B, Akmali M, Vessal G, Pakfetrat M, Raees Jalali GA, et al. Comparative effects of silymarin and vitamin E supplementation on oxidative stress markers, and hemoglobin levels among patients on hemodialysis. Ren Fail 2011;33:118-23.  Back to cited text no. 6
    
7.
Homsi E, de Brito SM, Janino P. Silymarin exacerbates p53-mediated tubular apoptosis in glycerol-induced acute kidney injury in rats. Ren Fail 2010;32:623-32.  Back to cited text no. 7
    
8.
Oliveira CS, Rodrigues AM, Nogueira GB, Nascimento MA, Punaro GR, Higa EM, et al. Moderate aerobic exercise on the recovery phase of gentamicin-induced acute kidney injury in rats. Life Sci 2017;169:37-42.  Back to cited text no. 8
    


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