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蝙蝠蛾擬青黴菌絲體萃取物對cisplatin誘導之小鼠腎毒性具有保護效果

Protection of Cisplatin-induced Nephrotoxicity in Mice by Paecilomyces hepiali Mycelium Extracts

摘要


順鉑(cisplatin)為目前常用的化療藥物之一,對多種癌症都有顯著療效,臨床應用廣泛,但本身也有強烈副作用包括噁心、嘔吐、腎毒性等。本研究利用cisplatin進行誘導腎損傷,以評估蝙蝠蛾擬青黴菌絲體萃取物是否具有預防性保護作用。試驗分為五組,每組8隻ICR雄性小鼠每日投予劑量分別為對照組5 ml/kg bw的生理食鹽水、誘導藥物組20 mg/kg bw的cisplatin、正對照組為200 mg/kg bw的Amifostine、酒萃物組500 mg/kg bw的蝙蝠蛾擬青黴菌絲體酒萃物、水萃物組500 mg/kg bw的蝙蝠蛾擬青黴菌絲體水萃物,各分別配合20 mg/kg bw的cisplatin。投予試藥10天,投藥後第七天注射cisplatin進行誘導,誘導96小時後犧牲。結果顯示,蝙蝠蛾擬青黴菌絲體酒萃物與水萃物組均可以降低BUN和creatinine的含量、對cisplatin誘導的腎毒性之腎臟指數均下降、並顯著降低由cisplatin誘導的腎組織中之組織病理學變化。且在細胞實驗中發現合併使用蝙蝠蛾擬青黴菌絲體萃取物與cisplatin處理癌細胞,對於癌細胞存活率並無影響,顯示蝠蛾擬青黴菌絲體萃取物並不影響化療藥物cisplatin抑制癌細胞生長的效果。總之,本研究的結果證實蝙蝠蛾擬青黴菌絲體兩種萃取物對cisplatin誘導的小鼠腎毒性有保護作用。

並列摘要


Cisplatin is a chemotherapy drug used to treat a number of cancers. Common side effects of cisplatin include nausea, vomiting, and nephrotoxicity. The aim of the present study was to investigate the protective effect of Paecilomyces hepiali mycelium extracts against cisplatin-induced nephrotoxicity. Mice were randomly divided into five groups, and orally administered with saline (negative control), 200 mg/kg bw amifostine (positive control), 500 mg/kg bw P. hepiali mycelium water extract, or 500 mg/kg bw P. hepiali mycelium ethanol extract every day for 11 days. Cisplatin (200 mg/kg bw) was administered by intraperitoneal injection on day 7. Clinical symptoms and the body weight of each mouse was recorded daily. At the end of the study, all mice were sacrificed, and blood and organs were collected for clinical chemistry and histopathological examinations. Results showed that the mean BUN and creatinine levels in mice pretreated with water or ethanol extract of P. hepiali mycelium were significantly lower than those without the pretreatment, suggesting that pretreatment of mice with P. hepiali mycelium extracts alleviated cisplatin-induced kidney damage. In addition, treatment of cisplatin with P. hepiali mycelium extracts did not affect the effect of cisplatin on the proliferation of cancer cells in vitro, suggesting that P. hepiali mycelium extracts have no effect on the antitumor activity of cisplatin. In summary, results of this study demonstrated protective effect of P. hepiali mycelium extracts on cisplatin-induced kidney injury in mice.

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