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    Milk Thistle (PDQ®): Complementary and alternative medicine - Health Professional Information [NCI] - Laboratory / Animal / Preclinical Studies

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    Silymarin has also been investigated as a possible adjunctive agent in mitigating some of the toxicity associated with chemotherapy agents. Silybin and silychristin exerted a protective effect on monkey kidney cells exposed to vincristine and especially cisplatin chemotherapy.[49] Silybin (200 mg/kg body weight) administration with cisplatin in rats resulted in statistically significant reductions in measures of kidney toxicity.[50] Significant decreases in weight loss, faster recovery of urinary osmolality measures, and depressions in the increase in activity of urinary alanine aminopeptidase ([AAP], a marker of kidney toxicity) were observed. Silybin had no effect on magnesium excretion or glomerular function. Silybin (2 g /kg body weight) administration in rats receiving cisplatin prevented reductions in creatinine clearance, increases in urea plasma levels, and large increases in urinary AAP.[51] No effect on magnesium excretion was observed. Silybin did not interfere with the antineoplastic effects of cisplatin or ifosfamide in germ cell tumors. In experiments with ovarian and breast cancer cell lines, silybin potentiated the effect of cisplatin and doxorubicin.[13] IdB 1,016, a form of silybin bound to a phospholipid complex, was found to enhance the activity of cisplatin against A2780 ovarian cancer cells but had no effect on its own.[52] Silybin increased the chemosensitivity of DU 145 prostate cancer cells resistant to chemotherapy.[53]

    Studies have also investigated the effect of silymarin on tumor initiation and promotion. Silymarin appears to have a chemopreventive effect through perturbations in the cell cycle, altering cell signaling that induces cellular proliferation, affecting angiogenesis, or through its anti-inflammatory properties.[1,7,13,19,54] These findings have been supported in human prostate, breast, ectocervical, ovarian, hepatic, leukemia, and epidermoid cell lines.[4,7,9,10,15,55] An investigation of the effect of silymarin on ultraviolet B radiation-induced nonmelanoma skin cancer in mice found that silymarin treatment significantly reduced tumor incidence (P < .003), tumor multiplicity (P < .0001), and tumor volume (P < .0001).[19] These findings suggest that silymarin plays a prominent role in the reduction of cancer cells and in preventing the formation of cancer cells. A number of studies have investigated the mechanism through, which silymarin may affect tumor promotion in mouse skin tumor models. Studies have found that silymarin reduces transcription of markers of tumor promotion and activity,[19] inhibits transcription of tumor promoters,[56] stimulates antioxidant activities,[19,23] interferes with cell signaling,[55] inhibits inflammatory actions,[19,22] and modulates cell-cycle regulation.[57]

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