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Protective Effect of Safflower Seed on Cisplatin-Induced Renal Damage in Mice via Oxidative Stress and Apoptosis-Mediated Pathways.

  • Park, Chan Hum1
  • Lee, Ah Young2
  • Kim, Ji Hyun2
  • Seong, Su Hui3
  • Jang, Gwi Yeong1
  • Cho, Eun Ju2
  • Choi, Jae Sue3
  • Kwon, Jungkee4
  • Kim, Young Ock1
  • Lee, Sang Won1
  • Yokozawa, Takako5
  • Shin, Yu Su1
  • 1 * Department of Medicinal Crop Research, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong 369-873, Republic of Korea. , (North Korea)
  • 2 † Department of Food Science and Nutrition, Pusan National University, Busan 46241, Republic of Korea. , (North Korea)
  • 3 ‡ Department of Food and Life Science, Pukyong National University, Busan 608-737, Republic of Korea. , (North Korea)
  • 4 § Department of Laboratory Animal Medicine, College of Veterinary Medicine, Chonbuk National University, Iksan 54596, Republic of Korea. , (North Korea)
  • 5 ¶ Graduate School of Science and Engineering for Research, University of Toyama, Toyama 930-8555, Japan. , (Japan)
Published Article
The American journal of Chinese medicine
Publication Date
Jan 01, 2018
DOI: 10.1142/S0192415X1850009X
PMID: 29298512


Cisplatin, a platinum chelate with potent antitumor activity against cancers of the testis, ovary, urinary bladder, prostate, and head and neck, has adverse effects on the kidney, bone marrow, and digestive organs, and its use is particularly limited by nephropathy as a side effect. In the present study, safflower seed extract was administered to a mouse model of cisplatin-induced acute renal failure to investigate its activity. Cisplatin (20[Formula: see text]mg/kg body weight) was administered by intraperitoneal injection to mice that had received oral safflower seed extract (100 or 200[Formula: see text]mg/kg body weight per day) for the preceding 2 days. Three days after the cisplatin injection, serum and renal biochemical factors; oxidative stress, inflammation, and apoptosis-related protein expression; and histological findings were evaluated. Cisplatin-treated control mice showed body-weight, food intake and water intake loss, and increased kidney weight, whereas the administration of safflower seed extract attenuated these effects ([Formula: see text], [Formula: see text]). Moreover, safflower seed extract significantly decreased the renal functional parameters urea nitrogen and creatinine in the serum ([Formula: see text] and [Formula: see text], respectively). Safflower seed extract also significantly reduced the enhanced levels of reactive oxygen species in the kidney observed following cisplatin treatment, with significance. The expression of proteins related to the anti-oxidant defense system in the kidney was down-regulated following cisplatin treatment, but safflower seed extract significantly up-regulated the expression of the anti-oxidant enzyme catalase. Furthermore, safflower seed extract reduced the overexpression of phosphor (p)-p38, nuclear factor-kappa B p65, cyclooxygenase-2, inducible nitric oxide synthase, ATR, p-p53, Bax, and caspase 3 proteins, and mice treated with safflower seed extract exhibited less renal histological damage. These results provide important evidence that safflower seed extract exerts a pleiotropic effect on several oxidative stress- and apoptosis-related parameters and has a renoprotective effect in cisplatin-treated mice.

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