Cisplatin (cis-diaminedichloroplatinum II) is one of the most effective chemotherapeutic agents and plays a major role in the treatment of a variety of human solid tumors including those of the head, neck, testis, ovary, and breast. 1)However, the nephrotoxicity of cisplatin limits the efficacy of this important anticancer drug.2) Although the pathogenesis of cisplatin-induced acute renal failure (ARF) has been the subject of many studies, the molecular mechanisms that underlie its toxicity are poorly understood. Some investigators have suggested that free radicals play an important role in cisplatin-induced nephrotoxicity, 3,4) and another proposed that reactive oxygen species (ROS), particularly the superoxide radical, play an important role in cisplatin-induced renal injury.5) It has also been reported that cisplatin-induced nephrotoxicity is closely associated with an increase in lipid peroxidation in the kidney. 6,7) In addition, cisplatin has been found to inhibit antioxidant activity 8) and to induce GSH depletion, which has been proposed to be involved in nephrotoxicity.9,10) Some evidence suggests that free radical scavengers and antioxidants ameliorate cisplatin-induced nephrotoxicity.11) The antioxidant DPPD (N,NЈ-diphenyl-pphenylenediamine) reduced nephrotoxicity in cisplatintreated rats, inhibited an increase in lipid peroxide level, and reduced the inhibition of p-aminohippurate transport in vitro.12,13) Actually, amifostine has been clinically approved as a cytoprotective agent during cisplatin therapy. It is known to act via a mechanism that involves the scavenging of free radicals, the donation of hydrogen ions to free radicals, the depletion of oxygen, and the binding to active derivatives of antineoplastic agents.14,15) Thus, as a part of our on-going screening program to evaluate the protective potentials of natural compounds, we investigated the nephroprotective activity of the ethanol extract of the roots of Brassica rapa in vitro and in vivo. The group Brassica rapa includes many significant crops such as the Chinese cabbage; in Italy this group is mainly represented by turnip tops [B. rapa L. subsp. sylVestris (L.) JANCH var. esculenta HORT.], which are used as a cooked vegetable and are known as "cime di rapa." In Korea, Brassica rapa is cultivated commercially in GangHwa County, Kyunggi Province. In previous studies on Brassica rapa, flavonoids (isorhamnetin, kaempferol, and quercetin glycosides), 16) phenylpropanoid derivatives, 16) indole alkaloids, 17) and sterol glucosides 17) were identified. The only report on the minor components of B. rapa involved the determination of glucosinolates, a group of secondary metabolites of b-thioglucose, which is characteristics of the genus of Brassica.17) It is generally assumed that flavonoid components are of great importance in view of their biological effects of the human metabolism, 18) but no report has been issued on the protective effect of B. rapa on cisplatin-induced nephrotoxicity. Therefore, we investigated whether the ethanol extract...

Cisplatin (cis-diaminedichloroplatinum II) is a highly effective antineoplastic DNA alkylating agent that is widely used to treat many cancers, such as, head and neck, ovarian, testicular, mammalian, and cervical cancer.1) However, although higher doses of cisplatin are more effective, many reversible and irreversible side effects including nephrotoxicity, neurotoxicity, bone marrow toxicity, gastrointestinal toxicity, and ototoxicity limit its therapeutic profile.2) The primary targets of cisplatin in the kidney are the proximal straight and distal convoluted tubules, in which it accumulates and promotes cellular damage via multiple mechanisms, such as, oxidative stress, DNA damage, and apoptosis. [3][4][5] Cisplatin nephrotoxicity can present as Fanconi-like syndrome, distal renal tubular acidosis, hypocalcemia, and acute kidney injury, the latter of which occurs in 20-30% of patients undergoing cisplatin treatment. 6) It has been demonstrated that cisplatin induces cell death of renal tubules, which is characterized by reduced glutathione (GSH) levels, and higher blood urea nitrogen (BUN), serum creatinine, and malondialdehyde (MDA) levels, which are suggestive of accelerated peroxidative processes. Furthermore, reactive oxygen species (ROS) are known to cause tissue damage by interacting with various macromolecules, such as, polyunsaturated fatty acids, in the cellular membrane. ROS are generated endogenously in renal cells, and are directly removed by endogenous antioxidants, such as, GSH and superoxide dismutase (SOD). It has been suggested that ROS upregulation is associated with an impaired glomerular filtration rate (GFR).7) On the other hand, antioxidants maintain intracellular reduced GSH concentrations, restore cellular defense mechanisms, block lipid peroxidation, and thus, protect real cells against the noxious effects of a wide variety of nephrotoxic agents. 8,9) Several studies have suggested that cisplatin induces ROS and reactive nitrogen species (RNS), which both deplete GSH and cause lipid peroxidation. [10][11][12] In particular, the hydroxyl radical is generated by the interaction between DNA and cisplatin, and attacks renal microsomal membranes and causes lipid peroxidation.13) Furthermore, the depletion of renal GSH may also increase MDA levels and the formations of stable proteincisplatin adducts, and decrease the activities of antioxidant enzymes, such as, SOD, catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx).14,15) Cisplatin is also known to increase the activities of the oxidant enzymes, such as aldehyde oxidase (AO) and xanthine oxidase (XO), which are major contributors to oxidant load in renal tissues. 16,17) Rubus coreanus (Rosaceae) is a perennial shrub found in southern part of Korea, and its dried unripe fruits have been used for centuries as an herbal medicine, particularly to improve libido.11) In one study undertaken to compare of antioxidant activities of seventy herbs used in Korean traditional medicine, Rubus coreanus demonstrated potent antiox...