Ginsenoside Rg5 Ameliorates Cisplatin-Induced Nephrotoxicity in Mice through Inhibition of Inflammation, Oxidative Stress, and Apoptosis
نویسندگان
چکیده
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.
منابع مشابه
Sumatriptan ameliorates renal injury induced by cisplatin in mice
Objective(s): Cisplatin (Cis) is an anticancer compound, which is used for the treatment of various cancers. Sumatriptan (Suma) is a selective agonist of 5-hydroxytryptamine 1B/1D (5HT1B/1D) receptor, which is prescribed for the management of migraine. It is well-established that Suma has anti-inflammatory and antioxidant properties. We have explored the protective effe...
متن کاملA H2S Donor GYY4137 Exacerbates Cisplatin-Induced Nephrotoxicity in Mice
Accumulating evidence demonstrated that hydrogen sulfide (H2S) is highly involved in inflammation, oxidative stress, and apoptosis and contributes to the pathogenesis of kidney diseases. However, the role of H2S in cisplatin nephrotoxicity is still debatable. Here we investigated the effect of GYY4137, a novel slow-releasing H2S donor, on cisplatin nephrotoxicity in mice. Male C57BL/6 mice were...
متن کاملZataria multiflora ameliorates cisplatin-induced testicular damage via suppression of oxidative stress and apoptosis in a mice model
Objective(s): Cisplatin (CP), as an anti-neoplastic drug, causes testicular damage. Zataria multiflora Boiss (ZM), a medicinal plant, has antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects of ZM against CP-induced testicular toxicity. Materials and Methods: In this experimental study, thirty-two adult male mice were randomly divided into four group...
متن کاملHydrogen sulfide ameliorates the kidney dysfunction and damage in cisplatin-induced nephrotoxicity in rat
Hydrogen Sulfide (H2S) prevents and treats a variety of disorders via its cytoprotective effects. However, the effects of H2S on rats with cisplatin (CP) nephrotoxicity are unclear. The aim was to study the effects of H2S on rats with CP nephrotoxicity. Thirty male Sprague-Dawley rats were divided into three groups: control group, nephrotoxic group received sing...
متن کاملPreventive effect of fermented black ginseng against cisplatin-induced nephrotoxicity in rats
BACKGROUND Fermented black ginseng (FBG) is processed ginseng by the repeated heat treatment and fermentation of raw ginseng. The protective effect and mechanism of FBG on cisplatin-induced nephrotoxicity was investigated to evaluate its therapeutic potential. METHODS The free radical scavenging activity of FBG was measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH). In addition, the protecti...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 8 شماره
صفحات -
تاریخ انتشار 2016