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      Salviae Radix Extract Prevents Cisplatin-Induced Acute Renal Failure in Rabbits

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          The present study was carried out to determine if salviae radix extract (SRE) exerts a beneficial effect against cisplatin-induced renal failure in rabbits. Rabbits were pretreated with SRE orally for 7 days, followed by cisplatin injection (5 mg/kg i.p.). Cisplatin injection caused a reduction in GFR, which was accompanied by an increase in serum creatinine levels. The fractional Na<sup>+</sup> excretion was increased by cisplatin injection. PAH uptake by renal cortical slices was inhibited by the administration of cisplatin. Such changes were prevented by SRE pretreatment. Cisplatin injection increased lipid peroxidation, which was prevented by SRE pretreatment. The protective effect of SRE was supported by morphological studies. Cisplatin injection reduced renal blood flow that was not affected by SRE pretreatment. Cisplatin treatment in vitro in renal cortical slices increased LDH release and lipid peroxidation, which were prevented by 0.05% SRE. These results indicate that lipid peroxidation plays a critical role in cisplatin-induced acute renal failure. SRE exerts a protective effect against renal cell injury induced by cisplatin, and its effect may be attributed to its antioxidant action. However, the underlying mechanism by which SRE has antioxidant action remains to be defined.

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          Most cited references 5

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          Plant-derived anticancer agents.

          Natural product drugs play a dominant role in pharmaceutical care. This is especially obvious in the case of antitumor drugs, as exemplified by paclitaxel (Taxol), vincristine (Oncovin), vinorelbine (Navelbine), teniposide (Vumon), and various water-soluble analogs of camptothecin (e.g., Hycamtin). The most efficient method of discovering drugs such as these (i.e. novel chemical prototypes that may function through unique mechanisms of action) is bioactivity-guided fractionation, and it is certain that additional natural product drugs, some of which should be useful for the treatment of humans, remain to be discovered. For the commercial procurement of structurally complex natural product drugs, isolation from plant material may be most practical. With the advent of combinatorial chemistry and high throughput screening, however, even greater progress may now be expected with natural product leads. While systemic drug therapy, to an appreciable extent based on natural products, has been the mainstay of pharmaceutical care, the logic of disease prevention is overwhelming. Bearing in mind the pandemic nature of cancer, a proposal is put forth to create a cancer chemoprevention drug formulation for utilization on a widespread basis by the general population. Cancer chemopreventive agents, many of which are natural products, are capable of preventing or inhibiting the process of carcinogenesis. As with other pharmaceutical agents useful for disease prevention, a pharmacoeconomic analysis of a cancer chemopreventive formulation would need to be considered, and the composition of the formulation should improve over time. Nonetheless, implementation should commence immediately.
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            Effect of cisplatin on renal function in rabbits: mechanism of reduced glucose reabsorption.

             Y. Kim,  H Byun,  Y H Kim (1995)
            This study was performed to determine the effect of cisplatin (cis-diamminedichloroplatinum II) on renal function in rabbits. Injection of a single i.p. dose of 4 mg/kg cisplatin caused an increase in fractional excretion of Na+ and K+ and a decrease in urine osmolality (Uosm), free-water reabsorption, (TcH2O), and urine to plasma creatinine ratio (U/Pcr). Urine flow was decreased following cisplatin treatment, which was accompanied by marked reduction in GFR. Cisplatin induced glucosuria, phosphaturia, and aminoaciduria. These results suggest that cisplatin results in impaired proximal tubular reabsorptive function and the renal concentrating defect. Cisplatin treatment impaired the accumulation of PAH and TEA and ouabain-sensitive oxygen consumption in renal cortical slices. Na(+)-K(+)-ATPase activity in renal cortical microsomes and basolateral membrane vesicles was significantly depressed in cisplatin-treated animals. Cisplatin treatment did not affect the Na(+)-dependent uptake of glucose and L-glutamate by brush-border membrane vesicles (BBMV), but caused a significant decrease in Na(+)-dependent succinate and H(+)-dependent TEA uptake. Morphological observations showed that cisplatin caused a focal loss of the microvillus brush border. These results suggest that (1) cisplatin induces oliguric acute renal failure in rabbits and (2) glucosuria induced by cisplatin was not due to a direct impairment of glucose transporter in brush-border membranes but due to an inhibition of Na(+)-pump activity and a decrease in area for active glucose reabsorption in the proximal tubule.
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              Role of mitochondria in cisplatin-induced oxidative damage exhibited by rat renal cortical slices


                Author and article information

                S. Karger AG
                22 June 2001
                : 88
                : 3
                : 241-246
                aDepartment of Internal Medicine, College of Oriental Medicine, Dongguk University, Gyuong-ju, and bDepartment of Physiology, College of Medicine, Pusan National University, Pusan, Korea
                45996 Nephron 2001;88:241–246
                © 2001 S. Karger AG, Basel

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                Figures: 4, Tables: 1, References: 29, Pages: 6
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