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

AKI occurs in 10-20% of the patients treated with AGs, presumably resulting in increased mortality and morbidity.3 Gentamicin (GEN), belonging to the AGfamily, is an important antibiotic used to treat a wide variety of bacterial infections, especially those caused by life-threatening gram-negative bacteria.4-6 However, ototoxicity and nephrotoxicity remain the serious side effects of GEN. Of note, nephrotoxicity isthe major adverse effect of GEN which develops in approximately 30% of the patients treated with GENfor more than 7 days.4,7 Importantly, GEN was demonstrated to negatively affect the cochlea, kidneys, and vestibular apparatus,leading to limited clinical use of GEN.8 Despite the above-mentioned issues as well as the introduction of newer and less toxic antibiotics, the unique characteristics of GEN, including broad-spectrum activity, rapid bactericidal action, post-antibiotic effects, chemical stability, low cost, and efficacy against bacteriaresistantto other antibiotics, have made GEN a first-line antibiotic in a wide variety of clinical situations.9-11 Importantly, accumulating evidence demonstrated that antioxidant compounds play crucialroles in the reduction of renal damages caused by GEN. There are also studies suggesting the protective effect of Silymarin (SM)against antibiotic-induced nephrotoxicity.12-14 SM is a flavonoid complex isolated from the seeds of milk thistle (Silybummarianum), which has been widely used as a natural remedy for the treatment of liver and gall bladder disorders, including hepatitis, cirrhosis, jaundice, and protection of liver from injuries caused by ischemia, radiation, alcohol abuse, iron overload, and environmental toxins.9,15 The aim of the present study was to investigate the protective effects of SMonthe prevention of GEN-induced nephrotoxicity in patients admitted to university-affiliated hospitals. Exclusion and inclusion criteria Patients were included in this study if they met the following criteria: hemodynamic stability (mean arterial blood pressure above 70 mmHg and/or systolic blood pressure above 90 mmHg); willingness to participate in the study; receiving GEN intravenously or intramuscularly for at least one week(a dose of 5mg/kg/day or 80-100 mg/ TDS;depending on the type of infection, GEN can be given once daily or several times a day); no confirmed history of AKI (including increased serum creatinine (Cr) levels equal to or greater than 0.3 mg/dL within 48 hours, increased Crlevels equal to or