摘要：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) 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. Financial support and sponsorship This study was supported financially by Isfahan University of Medical Sciences. Conflicts of interest There are no conflicts of interest.
