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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.


HPLC chromatograms of: GSLS (A); and steamed GSLS (B).
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nutrients-08-00566-f002: HPLC chromatograms of: GSLS (A); and steamed GSLS (B).

Mentions: Since the yield of saponins from stems-leaves was higher than those from the main roots and hair roots, ginseng stems-leaves saponins (GSLS) was used to obtain ginsenoside Rg5 in this study. The changes in ginsenoside compositions and HPLC chromatograms with the steaming of GSLS were shown in Figure 2. The results indicate that ginsenoside compositions changed significantly after steaming treatments. The levels of ginsenosides Rb1, Rb2, Rc, and Rd decreased dramatically under the high temperature. Ginsenoside Rg5, which was not present in GSLS, remarkably increased with the content of 78.56 mg/g after steaming treatment. Interestingly, the findings from our results are in agreement with those reported previously by Kim et al. [33], who employed autoclave steaming of ginseng roots at 120 °C for 2 h to get the highest content of Rg3 and Rg5.


Ginsenoside Rg5 Ameliorates Cisplatin-Induced Nephrotoxicity in Mice through Inhibition of Inflammation, Oxidative Stress, and Apoptosis
HPLC chromatograms of: GSLS (A); and steamed GSLS (B).
© Copyright Policy
Related In: Results  -  Collection

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

nutrients-08-00566-f002: HPLC chromatograms of: GSLS (A); and steamed GSLS (B).
Mentions: Since the yield of saponins from stems-leaves was higher than those from the main roots and hair roots, ginseng stems-leaves saponins (GSLS) was used to obtain ginsenoside Rg5 in this study. The changes in ginsenoside compositions and HPLC chromatograms with the steaming of GSLS were shown in Figure 2. The results indicate that ginsenoside compositions changed significantly after steaming treatments. The levels of ginsenosides Rb1, Rb2, Rc, and Rd decreased dramatically under the high temperature. Ginsenoside Rg5, which was not present in GSLS, remarkably increased with the content of 78.56 mg/g after steaming treatment. Interestingly, the findings from our results are in agreement with those reported previously by Kim et al. [33], who employed autoclave steaming of ginseng roots at 120 °C for 2 h to get the highest content of Rg3 and Rg5.

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.