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.
Highlights
Cisplatin, a potent anti-cancer drug, is widely used and highly effective against multiple types of tumors, involving breast, ovarian, head and neck, and lung [1]
These changes in body weight and organ index were significantly dose-dependently attenuated by P. quinquefolius (PQS) at doses of 150
Control group showed no significant difference compared with that in the mice treated with PQS high dose group (p < 0.05 or p < 0.01)
Summary
A potent anti-cancer drug, is widely used and highly effective against multiple types of tumors, involving breast, ovarian, head and neck, and lung [1]. Its side effects restrict its clinical use. Clinical trials have reported that the side effects of cisplatin included nephrotoxicity, electrolyte disturbance, myelotoxicity, hemolytic anemia, neurotoxicity and ototoxicity [2]. The main dose-limiting factor related to cisplatin is nephrotoxicity [3]. Acute kidney injury (AKI) is one of the major characteristics of cisplatin-induced renal toxicity, which is related to high morbidity and mortality [4]. Several studies have reported that cisplatin-induced AKI can be detected in early phase using novel biomarkers [5,6,7,8]. In the case AKI appears and its major cause is not cured, it may be hard to restore renal function, and even more complications can follow [9]
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