The pseudoginsenoside F11 ameliorates cisplatin-induced nephrotoxicity without compromising its anti-tumor activity in vivo

Abstract

The clinical use of cisplatin was severely limited by its associated nephrotoxicity. In this study, we investigated whether the pseudoginsenoside F11 had protective effects against cisplatin-induced nephrotoxicity. To clarify it, one in vivo model of cisplatin-induced acute renal failure was performed. The results showed that pretreatment with F11 reduced cisplatin-elevated blood urea nitrogen and creatinine levels, as well as ameliorated the histophathological damage. Further studies showed that F11 could suppress P53 activation, inverse the ratio of Bax/Bcl2 and the anti-oxidative and free radical levels induced by cisplatin, which in turn inhibited tubular cell apoptosis. Importantly, F11 enhanced rather than inhibited the anti-tumor activity of cispaltin in murine melanoma and Lewis lung cancer xenograft tumor models. Our findings suggested that administering F11 with cisplatin might alleviate the associated nephrotoxicity without compromising its therapeutic efficiency. This finding provides a novel potential strategy in the clinical treatment of cancer.

Sodium hydrogen sulfide (NaHS) ameliorates alterations caused by cisplatin in filtration slit diaphragm and podocyte cytoskeletal in rat kidney

“…Cisplatin (CP) is a well-known antineoplastic drug extensively used for treatment of different solid tumors, such as cervical, ovarian cancer and testicular cancer ( 1 , 2 ). However, it has been observed that CP accumulates in the kidney with a greater degree than other organs and so renal damage is the major dose- limiting side effect of this drug ( 2 , 3 ).…”

Increase in Protective Effect of Panax vietnamensis by Heat Processing on Cisplatin-Induced Kidney Cell Toxicity

“…Due to their particular structure not having a heat-labile C-20 glycoside, these saponins were gradually degraded to ocotillol genin, which exhibited the kidney cell protective effect in the in vitro model. Moreover, pseudoginsenoside F11, a minor ocotillol-type saponin in Panax ginseng, was reported to have a protective effect against cisplatin-induced acute renal failure in an in vivo model [30]. These findings could be explained by a study by Jeong et al, which described the metabolism of these saponins to ocotillol genin by gut microbiota in a human faecal suspension [39].…”

“…In our study, the kidney cell protective effect increased gradually with the increase of time and reached a maximum at 12 h. Most of the less polar saponins possessing the kidney cell protective effect are protopanaxadiol-type saponins, including G-Rg3, -Rk1, -Rg5, -Rh2, and -Rh3 [22,[35][36][37]. Only a few studies of the kidney protective effect of protopanaxatriol-type saponins (G-Rk3 and -Rh4) and ocotillol-type saponins (pseudoginsenoside F11) have been reported [30,31].…”

“…However, the nephroprotective effect of VG and its main constituents, ocotillol-type saponins, is not well studied. An in vivo study on the protective effect of pseudo-ginsenoside F11 against cisplatin-induced kidney injury conducted by Wang et al strongly suggested the potential nephroprotective effect of ocotillol-type saponins and their metabolite, ocotillol genin (OCT) [30].…”

Ancient Chinese Formula Qiong-Yu-Gao Protects Against Cisplatin-Induced Nephrotoxicity Without Reducing Anti-tumor Activity

“…Lewis lung cancer cell xenograft tumors were established in C57BL/6 mice as previously reported 33 . When the tumors had grown to 200–300 mm 3 , the mice were randomly assigned to 4 groups (n = 13 each).…”