Protective Effects of Silymarin on Gentamicin-Induced Nephrotoxicity in Infectious Patients: A Randomized Double Blinded Placebo-Controlled Clinical Trial

Background: Nephrotoxicity is one of the most important side effects of gentamicin (GEN). Accumulating evidence demonstrated the crucial roles of antioxidant compounds in the reduction of GEN-induced renal injuries. Silymarin (SM),an antioxidant agent,was demonstrated toimprove GEN-induced kidney damage. The aim of this clinical trial was to investigate the effect of SMon GEN-induced nephrotoxicity.
Methods: This randomized, double-blinded, placebo-controlled clinical trial was conducted from April 2017 to October 2019 on patients diagnosed with infectious diseases receiving GEN at least for 7 days. After approving the study and obtaining informed consents, 60 patients were included in this study. Patients in the treatment (30) and control (30) groups were given injectable GEN along with 140 mg of SM tablets or placebo orally three times a day, respectively. Demographic, laboratory, and therapeutic profilesof the patients were recorded. Urine and blood samples were collected before and on days 1, 2, 3, 5 and 7 after GEN administration and intervention.
Results: Sex, age, GEN indication and baseline glomerular filtration rateswere found to haveno effect on GEN nephrotoxicity. SM- and placebo-treated groups exhibited no significant differencesbetweenthe indications and intervals of GEN administration. The overall rate of GEN nephrotoxicity in the SM group was significantly lower than that in the placebo group (16.7% and 53.3%, respectively; p: 0.003). In addition, the risk of GEN nephrotoxicity in patients receiving placebowas significantly higher than those receivingSM(OR:12.69, 95%, CI: 1.38-116.74; p:0.03). Serum creatininewasfound to be significantly higher in the placebo-treated group than that in theSM-treatedgroup (p<0.05). However, the frequency of acute tubular necrosis on days 2, 3, 5, and 7 after GEN administration exhibited no significant differences between SM- and placebo-treated patients.
Conclusion: This study demonstratedthat SM could attenuate renal injury in GEN-treated patients.