RESUMO
We synthesised and biologically evaluated two new hybrid probes [131I]BPF-01 and [131I]BPF-02 which were built from three structural entities: benzothiazole-phenyl, fluorescein isothiocyanate (FITC), and iodine-131. These probes were designed for potential applications in assisting surgical procedures of solid cancers. The cytotoxicity study demonstrated that fluorescent probes BPF-01 (31.23 µg/mL) and BPF-02 (250 µg/mL) were relatively not toxic to normal immortalized human keratinocytes (HaCaT) cells, as indicated by the percentage of cell survival above 50 %. Furthermore, both probes displayed low to moderate anticancer activity against the breast cancer cells (MDA-MB-231) and prostate cancer cells (LNCaP and DU-145). The probe BPF-01 apparently showed an accumulation in the tumour tissues, as suggested by ex vivo fluorescence examinations. In addition, the cellular uptake study suggests that hybrid probe [131I]-BPF-01 was potentially accumulated in the MCF-7 cell line with the highest uptake of 16.11 ± 1.52 % after 2 h of incubation, approximately 50-fold higher than the accumulation of iodine-131 (control). The magnetic bead assay suggests that [131I]-BPF-02 and [131I]-BPF-02 showed a promising capability to interact with translocator protein 18 kDa (TSPO). Moreover, the computational data showed that the binding scores for ligands 7-8, BPF-01 and BPF-02, and [131I]-BPF-01 and [131I]-BPF-02 in the TSPO were considerably high. Accordingly, fluorescent probes BPF-01 and BPF-02, and hybrid probes [131I]BPF-01 and [131I]BPF-02 can be further developed for targeting cancer cells during intraoperative tumour surgery.
RESUMO
BACKGROUND: Renal dysfunction is a common complication in type 2 diabetes mellitus patients associated with oxidative damage which could be characterized by 8-iso-prostaglandin F2α and hydrogen peroxide level as oxidative stress markers. OBJECTIVE: The aim of our study is to determine if there is a difference in 8-iso-prostaglandin F2α and hydrogen peroxide levels between sulfonylurea and combination of metformin-sulfonylurea in diabetic patients. We also wanted to determine if these oxidative stress markers correlate with the estimated Glomerular Filtration Rate (eGFR). SUBJECTS AND METHODS: We conducted a cross-sectional study with inclusion of 55 patients with type 2 diabetes mellitus in Dr. Sitanala Tangerang Hospital, Indonesia with purposive sampling. The value of eGFR was obtained by serum creatinine levels, while the level of 8-iso-prostaglandin F2α was measured by ELISA and urinary hydrogen peroxide using FOX-1 (Ferrous Ion Oxidation Xylenol Orange 1). RESULTS: There was no difference in 8-iso-prostaglandin F2α and hydrogen peroxide level between the two groups (p=0.088 and p=0.848). Moreover, there was no difference in eGFR values between the two groups, measured by Cockroft-Gault, MDRD, and CKD-EPI. 8-iso-prostaglandin F2α (n=55) was positively correlated with eGFR based on Cockroft-Gault (r=0.382; p=0.009), whereas urinary hydrogen peroxide (n=47) also generate significant positive correlation with eGFR based on the MDRD equation (r=0.326; p=0.021). Linear regression analysis showed that 8-iso-prostaglandin F2α is the most predictive factor and the only significant factor for eGFR in Cockroft-Gault, MDRD and also CKDEPI, even after controlled by gender, age, BMI, HbA1c, systole, and H2O2. CONCLUSION: The two treatments did not have any significant differences in antioxidant activity. However, an increase of urinary 8-iso-prostaglandin F2. and hydrogen peroxide which correlates with eGFR in the total sample may play a significant role in the pathophysiology of diabetic nephropathy.
