Effects of D-methionine on cisplatin-induced toxicity in rats.
2015
Hochschulschrift
Zugriff:
103
Cisplatin is a widely used chemotherapy drug. However, the side effects of chemotherapy such as nephrotoxicity, gastrointestinal toxicity, neurotoxicity, ototoxicity limited its used. Early studies indicated that D-methionine is sulfur-containing essential amino acid, which exerts antioxidative activity and does not affect antitumor activity. Some reports have showed that D-methionine mitigates cisplatin-induced ototoxicity. While the research of the effects D-methionine on gastrointestinal toxicity and neurotoxicity remains unknown, we examined in this study whether D-methionine can decrease cisplatin-induced side effects or not. CCK-8 assay was used to determine the cytotoxicity of D-methionine co-culture with cisplatin on human renal proximal tubular cells (HK-2 cells). The western blot and RT-PCR were applied to determine cleaved caspase 7 and AQP1 expression, respectively. In animal study, rats were divided into three groups as follows: 1) saline control group, 2) cisplatin alone group (5 mg/kg/week, intraperitoneally once a week for 3 weeks) 3) combine D-methionine (300 mg/kg/day, once a day) with cisplatin group. The results showed that chronic cisplatin-administered rats significantly decrease in body weight, food intake, WBC (white blood count), MCV (mean corpuscular volume), platelet, serum potassium concentration, uric acid and catalase activity of rat kidney. In addition, the MCHC (mean corpuscular hemoglobin concentration), serum sodium concentration, serum blood urea nitrogen (BUN) and creatinine levels, kidney/body weight ratio and renal malondialdehyde (MDA) production were increased in cisplatin-treated rats. Histological analysis revealed that large numbers of leukocytes infiltrated in proximal tubules. Vacuolization, swelling and hyaline casts were also observed in renal tubules. D-methionine administration could significantly increase body weight, food intake, MCV (mean corpuscular volume), platelet, serum potassium concentration and significantly decrease kidney/body weight ratio and renal malondialdehyde production in rat kidney. Unfortunately, higher levels of serum blood urea nitrogen and creatinine in cisplatin-treated rats could not retard through D-methionine administration. Our results indicate that D-methionine could protect against cisplatin-induced weight loss and avoid anorexia. Therefore, we suggest that D-methionine may be potential adjuvants of cisplatin.
Titel: |
Effects of D-methionine on cisplatin-induced toxicity in rats.
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Autor/in / Beteiligte Person: | Chao, Pei-Tsen ; 趙珮岑 |
Link: | |
Veröffentlichung: | 2015 |
Medientyp: | Hochschulschrift |
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