The effect of arsenic bioaccumulation in liver, kidney, skin, muscle, and intestinal tissues of mirror carp (Cyprinus carpio carpio) was investigated on lipid peroxidation and certain antioxidant enzyme activities. In this study, three aquarium groups were formed from mirror carp: control group, 0.5-, and 1-mg/L arsenic concentrations. The fish were dissected after 1 month. Arsenic bioaccumulation, malondialdehyde (MDA) levels, catalase (CAT), and superoxide dismutase (SOD) enzyme activities were determined in the tissues. Results showed that arsenic was accumulated in liver, kidney, muscle, skin, and intestinal tissues. As the final product of lipid peroxidation, MDA levels were determined to have increased in all tissues with the exception of muscle. On the other hand, CAT and SOD enzyme activities in the fish tissues were decreased as compared to the control group. In the muscle tissue, differences were observed in the enzyme activities depending on arsenic concentration. Considering the increases in enzyme inhibition and MDA levels, liver was observed to be the main tissue affected in response to the arsenic toxicity.
Bortezomib is a highly selective and reversible inhibitor of the 26S proteasome. It has been approved for the treatment of patients with relapsed and refractory multiple myeloma. A number of studies have been conducted to evaluate the activity and safety of bortezomib either alone or in combination with several cytotoxic agents and radiation. In the current study, the efficacy of bortezomib alone or in combination with cisplatin and 5‑fluorouracil was evaluated in 4T1 breast cancer cells, a highly metastatic murine cancer cell line. Using MTT assay, IC50 values of cisplatin and 5‑fluorouracil were determined to be 14.2 and 8.9 µM for cisplatin and 5‑fluorouracil, respectively. The effects of different concentrations of cisplatin and 5‑fluorouracil in combination with two different concentrations of bortezomib were examined in the 4T1 cells. Statistically significant differences were found when 1 or 5 µM cisplatin was combined with 10 or 50 nM bortezomib. Similarly, 1 µM 5‑fluorouracil or 5 µM 5‑fluorouracil in combination with 10 nM bortezomib caused significant cell death as compared to treatment with single agents. However, 1 or 5 µM 5‑fluorouracil did not potentiate the effects of higher concentrations of bortezomib (50 nM). The effect of the combination of cisplatin, 5‑fluorouracil and bortezomib was determined by soft agar assay. It was confirmed that a combination of cisplatin and bortezomib was more effective than each drug as a monotherapy. Therefore, the combination of cisplatin and bortezomib should be tested further in clinical settings.
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