Effect of silymarin on cisplatin-induced renal tubular injuries in adult male rabbits

Effect of Silymarin Administration on Cisplatin Nephrotoxicity: Report from A Pilot, Randomized, Double‐Blinded, Placebo‐Controlled Clinical Trial

“…To the best of our knowledge, it is the first human study that has evaluated the possible renoprotective effect of silymarin against cisplatin nephrotoxicity. In contrast to animal and in vitro studies (Gaedeke et al ., ; Bokemeyer et al ., ; Karimi et al ., ; Yousef et al ., ; Sanchez‐Gonzalez et al ., ), this study showed that oral silymarin administration could not prevent cisplatin associated AKI and tubular dysfunction in clinical setting.…”

“…Cisplatin‐induced urinary magnesium wasting is common and if not corrected, up to 90% of patients will experience hypomagnesemia (Miller et al ., ; Moon et al ., ; Blachley and Hill, ; Lajer and Daugaard, ); therefore, regular serum magnesium monitoring following cisplatin infusion and administering supplemental magnesium have been recommended (Launay‐Vacher et al ., ). Results from animal studies have shown that pretreatment with silymarin flavonolignans may improve cisplatin‐induced tubular and glomerular dysfunctions (Gaedeke et al ., ; Bokemeyer et al ., ; Karimi et al ., ; Yousef et al ., ; Sanchez‐Gonzalez et al ., ). Although this seems to be clinically non‐significant, compared with pre‐cisplatin‐treatment values, our patients had significantly higher urinary magnesium and potassium wasting after three cisplatin‐containing chemotherapy courses; nevertheless, the difference between silymarin and placebo group did not reach statistical significance.…”

“…Several mechanisms such as induction of cell death via apoptosis and necrosis, inflammation, and generation of reactive oxygen species have been suggested for cisplatin nephrotoxicity (Dos Santos et al ., ; Miller et al ., ). To date, no study has shown that silymarin is a substrate or inhibitor of OCT2,whereas animal studies described its antiinflammatory and antioxidant properties (Gaedeke et al ., ; Bokemeyer et al ., ; Karimi et al ., ; Yousef et al ., ; Sanchez‐Gonzalez et al ., ).…”

“…Some studies had indicated that only low amount of silymarin flavonolignans, which are responsible for the potential renoprotective effects of silymarin, were recovered in urine by conventional silymarin formulation (Calani et al ., ; Hawke et al ., ). Therefore, urine silymarin concentrations were expected to be low in this study, while animal and cell culture studies have used higher doses or concentrations of silymarin (Gaedeke et al ., ; Bokemeyer et al ., ; Karimi et al ., ; Yousef et al ., ; Sanchez‐Gonzalez et al ., ).…”

“…Several in vitro and in vivo studies have addressed the promising protective effects of silymarin flavonolignans and flavonoids against cisplatin‐induced nephrotoxicity. Silymarin‐treated animals and cell cultures showed lower cisplatin nephrotoxicity as measured by urinary electrolyte wasting, kidney histologic changes, tissue caspase activity and inflammatory markers, and proteinuria without complicating chemotherapy (Gaedeke et al ., ; Bokemeyer et al ., ; Karimi et al ., ; Agarwal et al ., ; Yousef et al ., ; Sanchez‐Gonzalez et al ., ). Cisplatin‐associated nephrotoxicity is mediated in part by inflammatory and oxidative stress, therefore antiinflammatory and antioxidant agents including silymarin have been proposed to prevent cisplatin nephrotoxicity (Miller et al ., ; Gaedeke et al ., ; Bokemeyer et al ., ; Karimi et al ., ; Yousef et al ., ; Sanchez‐Gonzalez et al ., ).…”