ABSTRACT
OBJECTIVE: In this study, the impact of arbutin was examined in a gentamicin (GM)-induced nephrotoxicity model. MATERIALS AND METHODS: Forty adult male Wistar rats were randomly assigned to five groups including control group; GM group, and three groups of GM+arbutin (25, 50 and 75 mg/kg). One day after the last injection of GM, creatinine, urea, carbonyl, thiobarbituric acid-reacting substance (TBARs), ferric reducing antioxidant power (FRAP) and 8-hydroxyguanosine levels were assessed in serum samples. Left and right kidneys were used for biochemical assays and histological evaluation, respectively. RESULTS: Our data showed that the FRAP level (p<0.05), urea (p<0.001), creatinine (p<0.001), and 8-hydroxyguanosine (p<0.001) levels of serum samples, were increased in GM-treated rats compared to the controls. The serum levels of TBARS (p<0.001) and carbonyl increased in serum and renal tissue (p<0.001) of GM-treated animals. Conversely, arbutin attenuated serum creatinine, urea and 8-hydroxyguanosine, and TBARS (p<0.001). Administration of arbutin significantly decreased carbonyl levels in serum and renal tissue samples (p<0.001). Furthermore, the levels of FRAP increased in the serum (p<0.01) and renal tissue samples (p<0.001) of arbutin-treated animals. Histological staining showed that arbutin significantly inhibits kidney damages. CONCLUSION: Our data suggest that arbutin attenuates GM-induced nephrotoxicity through its free radicals-scavenging activity.
ABSTRACT
The quinolone-3-carboxylic acid scaffold is essential structure for antibacterial activity of fluoroquinolones such as ciprofloxacin. Modification of 3-carboxylic functionality in this structure can be used for switching its activity from antibacterial to anticancer. Accordingly, a series of C-3 modified ciprofloxacin derivatives containing N-(5-(benzylthio)-1,3,4-thiadiazol-2-yl)-carboxamide moiety was synthesized as novel anticancer agents. Most of compounds showed significant activity against MCF-7, A549 and SKOV-3 cancer cells in the MTT assay. In particular, compounds 13a-e and 13g were found to be as potent as standard drug doxorubicin against MCF-7 cell line (IC50s = 3.26-3.90 µM). Furthermore, the 4-fluorobenzyl derivatives 13h and 14b with IC50 values of 3.58 and 2.79 µM exhibited the highest activity against SKOV-3 and A549 cells, being as potent as doxorubicin. Two promising compounds 13e and 13g were further tested for their apoptosis inducing activity and cell cycle arrest. Both compounds could significantly induce apoptosis in MCF-7 cells, while compound 13e was more potent apoptosis inducer resulting in an 18-fold increase in the proportion of apoptotic cells at the IC50 concentration in MCF-7 cells. The cell cycle analysis revealed that compounds 13e and 13g could increase cell portions in the sub-G1 phase, inducing oligonucleosomal DNA fragmentation and apoptosis confirmed by comet assay.
