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Ginsenoside Rg5 Ameliorates Cisplatin-Induced Nephrotoxicity in Mice through Inhibition of Inflammation, Oxidative Stress, and Apoptosis

View Article: PubMed Central - PubMed

ABSTRACT

Although cisplatin is an effective anti-cancer agent that is widely used for treating various types of malignant solid tumors, the nephrotoxicity induced by cisplatin severely limits its clinical application. The present study was designed to explore the potential protective effect of ginsenoside Rg5, a rare ginsenoside generated during steaming ginseng, on cisplatin-induced nephrotoxicity in a mouse experimental model. The possible mechanisms underlying this nephroprotective effect were also investigated for the first time. Rg5 was given at doses of 10 and 20 mg/kg for 10 consecutive days. On Day 7, a single nephrotoxic dose of cisplatin (25 mg/kg) was injected to mice. Cisplatin administration resulted in renal dysfunction as evidenced by increase in serum creatinine (CRE) and blood urea nitrogen (BUN) levels. In addition, cisplatin increased the level of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), the makers of lipid peroxidation, and depleted glutathione (GSH) content and superoxide dismutase (SOD) activity in renal tissues. These effects were associated with the significantly increased levels of cytochrome P450 E1 (CYP2E1), 4-hydroxynonenal (4-HNE), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, nuclear factor-kappa B (NF-κB) p65, and cyclooxygenase-2 (COX-2) in renal tissues. However, pretreatment with ginsenoside Rg5 significantly attenuated the renal dysfunction, oxidative stress and inflammation response induced by cisplatin. Furthermore, ginsenoside Rg5 supplementation inhibited activation of apoptotic pathways through increasing Bcl-2 and decreasing Bax expression levels. Histopathological examination further confirmed the nephroprotective effect of Rg5. Collectively, these results clearly suggest that Rg5-mediated alleviation of cisplatin-induced nephrotoxicity may be related to its anti-oxidant, anti-apoptotic and anti-inflammatory effects.

No MeSH data available.


Effects of ginsenoside Rg5 on the protein expression of: Bax (A); and nuclear factor-kappa B (NF-κB) p65, and cyclooxygenase-2 (COX-2) (B). The protein expression was examined by Western blotting analysis in kidney tissues from normal, cisplatin, cisplatin + Rg5 (10 mg/kg), and cisplatin + Rg5 (20 mg/kg).
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nutrients-08-00566-f010: Effects of ginsenoside Rg5 on the protein expression of: Bax (A); and nuclear factor-kappa B (NF-κB) p65, and cyclooxygenase-2 (COX-2) (B). The protein expression was examined by Western blotting analysis in kidney tissues from normal, cisplatin, cisplatin + Rg5 (10 mg/kg), and cisplatin + Rg5 (20 mg/kg).

Mentions: To gain a better understanding of the anti-inflammatory effects of Rg5, we measured the expression levels of NF-κB p65 and COX-2 in each treatment group using immunohistochemical analysis and Western blotting analysis. As shown in Figure 9 and Figure 10, the expression of NF-κB p65 and COX-2 were negligible in the kidney tissue sections of normal group. However, the positive area of NF-κB p65 and COX-2 expression in the cisplatin control group was significantly increased compared to normal group. Importantly, administration of Rg5 for 10 days resulted in dose-dependent reduction of NF-κB p65 and COX-2 expression.


Ginsenoside Rg5 Ameliorates Cisplatin-Induced Nephrotoxicity in Mice through Inhibition of Inflammation, Oxidative Stress, and Apoptosis
Effects of ginsenoside Rg5 on the protein expression of: Bax (A); and nuclear factor-kappa B (NF-κB) p65, and cyclooxygenase-2 (COX-2) (B). The protein expression was examined by Western blotting analysis in kidney tissues from normal, cisplatin, cisplatin + Rg5 (10 mg/kg), and cisplatin + Rg5 (20 mg/kg).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037551&req=5

nutrients-08-00566-f010: Effects of ginsenoside Rg5 on the protein expression of: Bax (A); and nuclear factor-kappa B (NF-κB) p65, and cyclooxygenase-2 (COX-2) (B). The protein expression was examined by Western blotting analysis in kidney tissues from normal, cisplatin, cisplatin + Rg5 (10 mg/kg), and cisplatin + Rg5 (20 mg/kg).
Mentions: To gain a better understanding of the anti-inflammatory effects of Rg5, we measured the expression levels of NF-κB p65 and COX-2 in each treatment group using immunohistochemical analysis and Western blotting analysis. As shown in Figure 9 and Figure 10, the expression of NF-κB p65 and COX-2 were negligible in the kidney tissue sections of normal group. However, the positive area of NF-κB p65 and COX-2 expression in the cisplatin control group was significantly increased compared to normal group. Importantly, administration of Rg5 for 10 days resulted in dose-dependent reduction of NF-κB p65 and COX-2 expression.

View Article: PubMed Central - PubMed

ABSTRACT

Although cisplatin is an effective anti-cancer agent that is widely used for treating various types of malignant solid tumors, the nephrotoxicity induced by cisplatin severely limits its clinical application. The present study was designed to explore the potential protective effect of ginsenoside Rg5, a rare ginsenoside generated during steaming ginseng, on cisplatin-induced nephrotoxicity in a mouse experimental model. The possible mechanisms underlying this nephroprotective effect were also investigated for the first time. Rg5 was given at doses of 10 and 20 mg/kg for 10 consecutive days. On Day 7, a single nephrotoxic dose of cisplatin (25 mg/kg) was injected to mice. Cisplatin administration resulted in renal dysfunction as evidenced by increase in serum creatinine (CRE) and blood urea nitrogen (BUN) levels. In addition, cisplatin increased the level of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), the makers of lipid peroxidation, and depleted glutathione (GSH) content and superoxide dismutase (SOD) activity in renal tissues. These effects were associated with the significantly increased levels of cytochrome P450 E1 (CYP2E1), 4-hydroxynonenal (4-HNE), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, nuclear factor-kappa B (NF-κB) p65, and cyclooxygenase-2 (COX-2) in renal tissues. However, pretreatment with ginsenoside Rg5 significantly attenuated the renal dysfunction, oxidative stress and inflammation response induced by cisplatin. Furthermore, ginsenoside Rg5 supplementation inhibited activation of apoptotic pathways through increasing Bcl-2 and decreasing Bax expression levels. Histopathological examination further confirmed the nephroprotective effect of Rg5. Collectively, these results clearly suggest that Rg5-mediated alleviation of cisplatin-induced nephrotoxicity may be related to its anti-oxidant, anti-apoptotic and anti-inflammatory effects.

No MeSH data available.