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. 2012 Sep;3(9):637-43.

The Role of Magnesium Supplementation in Cisplatin-induced Nephrotoxicity in a Rat Model: No Nephroprotectant Effect

Farzaneh Ashrafi  1 , Sara Haghshenas, Mehdi Nematbakhsh, Hamid Nasri, Ardeshir Talebi, Fatemeh Eshraghi-Jazi, Zahra Pezeshki, Tahereh Safari
Affiliations

The Role of Magnesium Supplementation in Cisplatin-induced Nephrotoxicity in a Rat Model: No Nephroprotectant Effect

Farzaneh Ashrafi et al. Int J Prev Med. 2012 Sep.

Abstract

Objectives: Cisplatin (CP) is used as the commonest drug to treat solid tumors. It is accompanied by a nephrotoxicity side effect. The main objective of this study is to investigate the protective role of magnesium (Mg) supplementation in CP-induced nephrotoxicity in a rat model.

Methods: Twenty-nine Wistar rats were randomly assigned to four groups (1-4). Groups 1-3 received 20, 80, and 200 mg/kg magnesium sulfate respectively, for 10 days, but on day 3, a single dose of CP (7 mg/kg, i.p.) was also injected. Group 4 (positive control group) received the same regimen of Groups 1-3 except saline instead magnesium sulfate. One week after CP administration, blood samples were obtained and all animals were killed for kidney histopathological investigations.

Results: All CP-treated animals lost weight, and the percentage of weight loss in Group 1 (low dose Mg sulfate treated) was significantly higher compared with the positive control group (Group 4, P < 0.05). The increase in blood urea nitrogen (BUN) and creatinine (Cr) levels in serum in Group 1 were more than those in other groups (P < 0.05). No statistical differences were observed in serum magnesium, nitrite, and total protein levels among the groups. The kidney tissue damage in Groups 1-3 was not significantly different when compared with Group 4. Moreover, the kidney and testis weights in Group 1 were significantly greater than those in the positive control group (P < 0.05).

Conclusion: Regarding the BUN and Cr levels in the serum, kidneys weight, and the histopathological study, the low dose of Mg supplementation intensifies kidney toxicity and renal dysfunction in CP-induced nephrotoxicity in the rat model. However, the protective role of Mg with moderate and high doses is not certain.

Keywords: Cisplatin; magnesium; nephrotoxicity; rat.

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Conflict of interest statement

Conflict of Interest: None declared

Figures

Figure 1
Figure 1
Serum levels of BUN (above) and Cr (below) in the four experimental groups 1 week after CP administration. Significant difference was observed between Group 1 and others groups (P< 0.05). Groups 1–4, respectively, received 20, 80, 200 mg/kg magnesium sulfate, and saline for 10 days plus a single dose of CP (7 mg/kg, i.p.) in day 3. One-way ANOVA was applied to compare the parameters between the groups
Figure 2
Figure 2
The percentage weight change, total kidney weight/100 g of body weight, and total testis weight/100 g of body weight of animals in the four groups 1 week after CP administration. One-way ANOVA was applied to compare groups with regard to the parameters. Significant difference was observed between Groups 1 and 4 (P< 0.05). Groups 1–4, respectively, received 20, 80, 200 mg/kg magnesium sulfate, and saline for 10 days plus a single dose of CP (7 mg/kg, i.p.) in day 3
Figure 3
Figure 3
The images (100×) of kidney tissue. (a) Group 1; low dose of magnesium + cisplatin, (b) Group 2; moderate dose of magnesium + cisplatin, (c) Group 3; high dose of magnesium + cisplatin, (d) Group 4; saline + cisplatin. Although the higher scores of damage were obtained in Groups 1 (a) and 4 (d), but no significant differences were detected between the groups
See this image and copyright information in PMC

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