Nephroprotective Effects of Saponins from Leaves of Panax quinquefolius against Cisplatin-Induced Acute Kidney Injury

Abstract

Abstract:Although cisplatin is an anticancer drug that has activity against malignant tumor, it often causes nephrotoxicity. Previous reports have confirmed that the saponins from the leaves of P. quinquefolium (PQS) exerted many pharmacological activities. However, the renoprotective effects of PQS were still unknown. The purpose of the present research was to discuss renoprotective effect of PQS in a mouse model of cisplatin-induced acute kidney injury (AKI). The levels of blood urea nitrogen (BUN) and serum creatinine (CRE) were evidently increased in cisplatin-intoxicated mice, which were reversed by PQS. Renal oxidative stress, evidenced by increased malondialdehyde (MDA) level and decline of glutathione (GSH) and superoxide dismutase (SOD) activities, was significantly alleviated by PQS pretreatment. The suppression of inflammatory response by PQS was realized through the decrease the mRNA expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in kidney tissues, which were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Simultaneously, the overexpression of cytochrome P450 E1 (CYP2E1) and heme oxygenase-1 (HO-1) were attenuated by PQS. Furthermore, the effects of Western blotting demonstrated that PQS administration significantly suppressed the protein expression levels of nicotinamide adenine dinucleotide phosphate oxidase type 4 (Nox4), cleaved Caspase-3, cleaved Caspase-9, Bax, nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), suggesting the inhibition of apoptosis and inflammation response. Overall, PQS may possess protective effects in cisplatin-induced AKI through suppression of oxidative stress, inflammation and apoptosis.

Treatment with melatonin and selenium attenuates docetaxel‐induced apoptosis and oxidative injury in kidney and testes of mice

“…Caspases have major roles in initiating degradation phases of apoptosis (Uğuz et al, ). Therefore, the current results confirmed the apoptosis and caspase data related to DTX (Gan et al, ; Hussein et al, ; Ma et al, ). However, we showed cell‐specific protective role of MEL and Se on the apoptosis level and caspase activation in the normal kidney and testes of DTX group.…”

“…Cellular stress induces stimulation of intrinsic apoptotic pathway and, in turn, activates several protein families including the Bcl‐2 family. When Bcl‐2 is activated by cellular oxidative stress, casp‐9 is directly cleaved, resulting in other caspase activation including casp‐3 (Kahya et al, ; Ma et al, ). After observation of increased oxidative stress and apoptosis levels in kidneys and testes, we examined the potential protective effects of MEL and Se on the caspase changes in the DTX‐induced kidney and testes oxidative toxicity.…”

“…However, the role of DTX in the apoptosis and caspase‐dependent processes is not fully understood, although some reports are present on cisplatin‐ and doxorubicin‐induced caspase activity in kidneys and testes. It was shown that cisplatin‐induced oxidative damage and apoptosis were decreased through up‐regulation of LPx, casp‐3 and casp‐9 and down‐regulation of GSHPx and R‐GSH in kidneys of mice (Ma et al, ), testes of rats (Hussein, Mohamed, Shalaby, Abd El‐Haleem, & Abd El Motteleb, ) and testes cell line (Gan et al, ). It was reported that doxorubicin‐induced increases of apoptosis, casp‐3 and casp‐9 were diminished in the breast cancer cells by MEL pre‐incubation (Koşar et al, ).…”

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“…The results of the present study revealed that caspase-9 level was induced in cis-treated mice. These results are in agreement with other studies 67,68 . A previous study reported that apoptotic cell death in renal tubule cell was caused by cis through the generation of reactive oxygen species, which activate the pro-apoptotic Bcl-2 family member Bax, which as a consequence induces mitochondrial permeability transition, causing the release of cytochrome c, caspase-9 activation, and entry into the apoptosis execution phase 69 .…”

Supplementation of American ginseng berry extract mitigated cisplatin-evoked nephrotoxicity by suppressing ROS-mediated activation of MAPK and NF-κB signaling pathways

“…Renal oxidative stress, apoptosis and inflammation have been considered as potential mechanisms underlying nephrotoxicity caused after cisplatin exposure (Ma et al, 2017) . In most cases, cisplatin appears in the plasma and passes through renal tubular epithelial cells, to activate numerous pro-inflammatory cytokines, such as TNF-α, IL-1β, and to induce the generation of the inflammatory mediators iNOS and COX-2 (Honma et al, 2013;Ma et al, 2015) .…”