Silybin dihemisuccinate, a water soluble form of the flavonoid silymarin (derived from milk thistle), protected rat livers from peroxidation and glutathione depletion caused by acetaminophen when it was injected intravenously (Campos et al. 1989). Liver protection was further evidenced by limited increases of aminotransaminases following toxic acetaminophen doses.

In a double-blind, placebo-controlled clinical trial, the use of silymarin with hepatotoxic psychotropic drugs (butyrophenones and phenothiazines) was evaluated (Palasciano et al. 1994). Sixty patients were enrolled in this study and were randomized into four groups of 15 to receive treatment for 90 days with either silymarin (800 mg/day) or placebo along with psychotropic drugs. Treatment with silymarin reduced serum levels of malondialdehyde, aspartate aminotransferase, and alanine aminotransferase, indicators of lipoperoxidation and hepatotoxicity. Submaximal doses of silymarin reduced the hepatotoxicity associated with treatment with butyrophenones or phenothiazines.

Silibinin (200 mg/kg IV), the main component of milk thistle extract, administered to rats one hour prior to treatment with a single injection of cisplatin (5 mg/kg) demonstrated nephroprotectant activity (Gaedeke et al. 1996). The effects of cisplatin on proteinuria and creatinine clearance were prevented completely by prior administration of silibinin. Proximal tubular functional impairment also was ameliorated. Kidney function was not affected by silbinin alone. However, concurrent administration of silibinin with cisplatin and ifosfamide significantly inhibited the anticancer effect of cisplatin and ifosfamide on human testicular cancer in vitro (Bokemeyer et al. 1996).

A rat study investigated whether silibinin treatment attenuated cyclosporin A toxicity on endocrine and exocrine pancreas (von Schonfeld et al. 1997). Rats were treated for 8 days with cyclosporin A, silibinin, or both. On day 9, endocrine and exocrine pancreatic functions were tested in vitro; blood glucose levels in vivo were higher in rats treated with cyclosporin A, while glucose levels in those treated with silibinin did not change. Insulin secretion in vitro was inhibited after treatment with silibinin, but amylase secretion was not affected. After treatment with cyclosporin A, both insulin and amylase secretion were reduced. Silibinin and cyclosporin A had additive inhibitory effects on insulin secretion, but silibinin attenuated cyclosporin A-induced inhibition of amylase secretion. Despite cyclosporin A treatment, amylase secretion was restored to normal with the highest dose of silibinin.

Bokemeyer C, Fels LM, DunnT, et al. Silibinin protects against cisplatin-induced nephrotoxicity without compromising cisplatin on isosfamide anti-tumor activity. Br J Cancer. 1996;74:2036-2041.

Campos R, Garrido A, Guerra R, et al. Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Med. 1989;55:417-419.

Gaedeke J, Fels LM, Bokemeyer C, et al. Cisplatin nephrotoxicity and protection by silibinin. Nephrol Dial Transplant. 1996;11:55-62.

Palasciano G, Portincasa P, Palmieri V, Ciani D, Vendemiale G, Altomare E. The effect of silymarin on plasma levels of malon-dialdehyde in patients receiving long-term treatment with psychotropic drugs. Curr Therapeut Res. 1994;55(5):537-545.

von Schonfeld J, Weisbrod B, Muller MK. Silibinin, a plant extract with antioxidant and membrane stabilizing properties, protects exocrine pancreas from cyclosporin A toxicity. Cell Mol Life Sci. 1997;53(11-12):917-920.