The aim of this study is to examine the protective effect of naringenin-oxime (NOX) on cisplatin-induced major organ toxicity and DNA damage in rats. Thirty-five male Wistar albino rats were equally split into five groups as follows: control (i.p., 0.1 ml of saline), Cis administration (i.p., 7 mg/kg b.w.), NOX treatment (i.p., 20 mg/kg b.w., daily for ten days), Cis + NOX20, and Cis + NOX40 combination (i.p., 20 and 40 mg/kg b.w., daily for ten days). Serum and peripheral blood mononuclear leukocytes (PBMC) were obtained from blood. Malondialdehyde, glutathione, total antioxidant and oxidant status, and catalase were measured in serum, liver, and kidney, and oxidative stress index was calculated. In parallel, paraoxonase and arylesterase activities were tested in liver and serum. We used 8-OHdOG as a marker for DNA damage in serum via ELISA and in PMBC via comet assay. Treatment with Cis elevated the levels of serum biochemical parameters, oxidative stress, and DNA damage. Pretreatments of NOX restored biochemical and oxidative stress parameters in serum, renal, and liver tissues (p < 0.01) and reduced 8-OHdG level, a finding further supported by comet assay in PBMC. Observations of the present study support the fact that treatment with NOX prevents Cis-induced hepatotoxicity, nephrotoxicity, and genotoxicity by restoring antioxidant system.

Selective inhibition with sulphonamides of carbonic anhydrase (CA) IX reduces cell proliferation and induces apoptosis in human cancer cells. The effect on CA IX expression of seven previously synthesised sulphonamide inhibitors, with high affinity for CA IX, as well as their effect on the proliferation/apoptosis of cancer/normal cell lines was investigated. Two normal and three human cancer cell lines were used. Treatment resulted in dose- and time-dependent inhibition of the growth of various cancer cell lines. One compound showed remarkably high toxicity towards CA IX-positive HeLa cells. The mechanisms of apoptosis induction were determined with Annexin-V and AO/EB staining, cleaved caspases (caspase-3, caspase-8, caspase-9) and cleaved PARP activation, reactive oxygen species production (ROS), mitochondrial membrane potential (MMP), intracellular pH (pHi), extracellular pH (pHe), lactate level and cell cycle analysis. The autophagy induction mechanisms were also investigated. The modulation of apoptotic and autophagic genes (Bax, Bcl-2, caspase-3, caspase-8, caspase-9, caspase-12, Beclin and LC3) was measured using real time PCR. The positive staining using γ-H2AX and AO/EB dye, showed increased cleaved caspase-3, caspase-8, caspase-9, increased ROS production, MMP and enhanced mRNA expression of apoptotic genes, suggesting that anticancer effects are also exerted through its apoptosis-inducing properties. Our results show that such sulphonamides might have the potential as new leads for detailed investigations against CA IX-positive cervical cancers.

Carbonic anhydrase IX (CA IX) has recently been validated as an antitumor/antimetastatic drug target. In this study, we examined the underlying molecular mechanisms and the anticancer activity of sulfonamide CA IX inhibitors against cervical cancer cell lines. The effects of several sulfonamides on HeLa, MDA-MB-231, HT-29 cancer cell lines, and normal cell lines (HEK-293, PNT-1A) viability were determined. The compounds showed high cytotoxic and apoptotic activities, mainly against HeLa cells overexpressing CA IX. We were also examined for intracellular reactive oxygen species (ROS) production; intra-/extracellular pH changes, for inhibition of cell proliferation, cellular mitochondrial membrane potential change and for the detection of caspase 3, 8, 9, and CA IX protein levels. Of the investigated sulfonamides, one compound was found to possess high cytotoxic and anti-proliferative effects in HeLa cells. The cytotoxic effect occurred via apoptosis, being accompanied by a return of pHe/pHi towards normal values as for other CA IX inhibitors investigated earlier.

In recent years, there is an increased research interest for plants which are natural sources of antioxidants. Lepidium sativum Subsp spinescens L., commonly found in South West Asia, is a plant known as a healthy nutritional source containing bio-molecules that carry anti-hypertensive, hypoglycemic, anti-asthmatic, antispasmodic, hepato-protective, chemoprotective, anti-inflammatory and anti-oxidant effects. In this study, we aimed to investigate the antioxidant content and activity of Lepidium sativum Subsp spinescens L. methanol extract on cancer cells. Methanol extract of dried Lepidium sativum Subsp spinescens L. was prepared. Total amount of phenolic compounds was determined by Slinkard and Singleton method using Folin-Ciocalteu reagent. Total flavonoid amount was determined according to Zhishen method. Antioxidant activity of the extract was evaluated by CUPRAC and ABTS radical scavenging activity assays. Cytotoxic effects of the plant extract on colon and endometrium cancer cells, and human peripheral lymphocyte cells were investigated in vitro by MTT and neutral red assays. Furthermore, the plant extract was investigated for necrotic effects by LDH assay; apoptotic activity by DNA ladder fragmentation, ELISA and acridine orange/ethidium bromide staining; and genotoxic effect by comet assay methods. Methanol extract of Lepidium sativum Subsp spinescens L. was found to have a high content of phenolic and flavonoid compounds. The extract showed significant antioxidant activity and also cytotoxic activity on colon and endometrium cancer cells in a concentration-dependent manner. Apoptotic activity and genotoxic effects were significantly increased, especially with 200 μg/ml concentrations at 48 hours incubation. In conclusion, it was determined that the extract evaluated in this study could be a natural source of antioxidants. Further molecular studies explaining chemo-preventive and chemotherapeutic effects on cancer cells are required to support anticancer efficacy of the plant.

Carbonic anhydrase IX (CAIX) is a hypoxia-related protein that plays a role in proliferation in solid tumours. However, how CAIX increases proliferation and metastasis in solid tumours is unclear. The objective of this study was to investigate how a synthetic CAIX inhibitor triggers apoptosis in the HeLa cell line. The intracellular effects of CAIX inhibition were determined with AO/EB, AnnexinV-PI, and γ-H2AX staining; measurements of intracellular pH (pHi), reactive oxygen species (ROS), and mitochondrial membrane potential (MMP); and analyses of cell cycle, apoptotic, and autophagic modulator gene expression (Bax, Bcl-2, caspase-3, caspase-8, caspase-9, caspase-12, Beclin, and LC3), caspase protein level (pro-caspase 3 and cleaved caspase-3, -8, -9), cleaved PARP activation, and CAIX protein level. Sulphonamide CAIX inhibitor E showed the lowest IC50 and the highest selectivity index in CAIX-positive HeLa cells. CAIX inhibition changed the morphology of HeLa cells and increased the ratio of apoptotic cells, dramatically disturbing the homeostasis of intracellular pHi, MMP and ROS levels. All these phenomena consequent to CA IX inhibition triggered apoptosis and autophagy in HeLa cells. Taken together, these results further endorse the previous findings that CAIX inhibitors represent an important therapeutic strategy, which is worth pursuing in different cancer types, considering that presently only one sulphonamide inhibitor, SLC-0111, has arrived in Phase Ib/II clinical trials as an antitumour/antimetastatic drug.

Acetylcholinesterase inhibitors, including Neostigmine, have been used to reverse neuromuscular blockage for many years. Sugammadex reverses this blockage using its gamma cyclodextrin ring, a mechanism that differs from that of cholinesterases and so circumvents the side effects of Neostigmine. Although the superiority of Sugammadex to Neostigmine has been outlined in several clinical studies, to our knowledge, there is not any research into cell culture that compares the cytotoxic, genotoxic and apoptotic effects of the two drugs. Hence, this is the first study to compare the cytotoxic, genotoxic and apoptotic effects of different dosages of both drugs on human embryonic renal (HEK-293) cells. In this study, the cytotoxicity, genotoxicity and apoptotic effects of Sugammadex and Neostigmine on HEK-293 cells were analyzed with using the MTT, Comet Assay and Flow Cytometric Annexin-V methods, respectively. The results demonstrate that Neostigmine at 50, 100, 250, and 500 µg/mL is more cytotoxic than equivalent dosages of Sugammadex. Neostigmine at 500 and 1000 µg/mL was found to be more genotoxic, and Neostigmine at 500 µg/mL had a statistically higher risk of causing apoptosis and necrosis than Sugammadex (p<0.05). Neostigmine administered in-vitro in the same doses as Sugammadex had greater cytotoxic, genotoxic and apoptotic effects on HEK-293 cells.

Background and objectives: The aim of this study was to research oxidative stress and thiol/disulphide homeostasis in Graves’ patients. Materials and Methods: The study included 33 Graves’ patients (research group) and 35 healthy subjects (control group). Serum oxidative stress and thiol/disulphide homeostasis (a new and automated spectrophotometric method developed by Erel and Neselioglu) parameters were studied and compared between the groups. Results: The native and total thiol levels and the native thiol/total thiol ratio were lower in patients with Graves’ disease compared to the control group (p < 0.001, p < 0.001, and p = 0.006, respectively). TOS (total antioxidant status), PC (protein carbonyl), OSI (Oxidative stress index), and disulphide/native thiol and disulphide/total thiol ratios were determined to be higher in the Graves’ disease group than in the control group (p < 0.001, p = 0.001, p = 0.001, p = 0.004, and p = 0.006, respectively). In the Graves’ disease group, the free triiodothyronine (FT3) and free thyroxine (FT4) levels were significantly positively correlated with impaired thiol/disulphide homeostasis and oxidative stress parameters (p < 0.05). Conclusion: The results of the current study demonstrated that oxidative stress and thiol/disulphide homeostasis increased towards disulphide formation due to thiol oxidation in Graves’ disease. In addition, a positive correlation of FT3 and FT4 was observed with oxidative stress parameters and impaired thiol/disulphide homeostasis.

The synthesis, spectroscopic properties, and in vitro cytotoxicity activity of a series of various salen-based triboron complexes have been designed and prepared from hemi-salen (L 1 H 3 -L 4 H 3 ) ligands and BF 3 ÁEt 2 O or BPh 3 under simple reaction conditions. The hemi-salen (L 1 H 3 -L 4 H 3 ) ligands and their BF 2 or BPh 2 chelating triboron complexes were characterized by means of NMR ( 1 H, 13 C, 19 F, and 11 B) spectra, FT-IR spectra, UV/VIS spectra, fluorescence spectra, mass spectra, melting point, as well as elemental analysis. The triboron [L (1 -4) (BF 2 ) 3 ] and [L (1 -4) (BPh 2 ) 3 ] complexes were investigated for their absorption and emission properties, and these complexes are also good chelates towards boron(III) fragments such as BF 2 or BPh 2 quantum yield in solution reaching up to 38%. The hemisalen (L 1 H 3 -L 4 H 3 ) ligands and their BF 2 or BPh 2 chelating triboron complexes were tested for the in vitro anticancer activity against various cancer and normal cells (HeLa, DLD-1, ECC-1, PC-3, PNT-1A, and CRL-4010), and it was found that the cell viability of cancer cells was decreased while most of the healthy cells could still be viable. Also, the cytotoxicity studies showed that anticancer activity of hemi-salenligands showing the strongest cytotoxic effect in PC-3 cells were found to exhibit anticancer activity with apoptosis by increasing the level of ROS in the PC-3 cells.