Protective Effect of Boric Acid Against Ochratoxin A-Induced Toxic Effects in Human Embryonal Kidney Cells (HEK293): A Study on Cytotoxic, Genotoxic, Oxidative, and Apoptotic Effects.

The present study evaluates the protective properties of boric acid (BA) against the toxic effects induced by ochratoxin A (OTA) in human embryonic kidney cells (HEK293). The focus is on various parameters such as cytotoxicity, genotoxicity, oxidative stress, and apoptosis. OTA is a known mycotoxin that has harmful effects on the liver, kidneys, brain, and nervous system. BA, on the other hand, a boron-based compound, is known for its potential as a vital micronutrient with important cellular functions. The results show that BA administration not only increases cell viability but also mitigates the cytotoxic effects of OTA. This is evidenced by a reduction in the release of lactate dehydrogenase (LDH), indicating less damage to cell membranes. In addition, BA shows efficacy in reducing genotoxic effects, as the frequency of micronucleus (MN) and chromosomal aberrations (CA) decreases significantly, suggesting a protective role against DNA damage. In addition, the study shows that treatment with BA leads to a decrease in oxidative stress markers, highlighting its potential as a therapeutic intervention against the deleterious effects of OTA. These results emphasize the need for further research into the protective mechanisms of boron, particularly BA, in combating cell damage caused by OTA.

Novel Coumarin Derivatives Containing a Triazole Moiety: A Study on Synthesis, Cytotoxicity, Membrane Dysfunction, Apoptosis, Cell Cycle, and Antiangiogenic Effects.

BACKGROUND: Coumarin is a functional compound with a pronounced wide range of biological activities and has recently been shown to have anticancer effects on various human cancer cells. Cisplatin is widely used in treating many cancers, but its effectiveness is limited due to acquired resistance and dose-related side effects. OBJECTIVE: This study aimed to reveal the chemosensitizing ability of novel synthesized coumarin-triazole hybrid compounds (3a-f) compared to the cisplatin in A549, MCF-7, and HeLa cancer cells. METHODS: Cytotoxicity was determined by MTT assay. Lactate dehydrogenase (LDH), antioxidant/oxidant status, and DNA fragmentation were determined spectrophotometrically using commercial kits. Muse™ Cell Analyzer was used to assess cell cycle progression. Pro/anti-apoptotic gene expressions were determined by Real-Time qPCR. The antiangiogenic activity was determined by VEGF expression and Hen's chorioallantoic membrane model. RESULTS: Compounds 3c, -d, -e, and -f potentiated the cisplatin-induced cytotoxicity by increasing LDH release and DNA fragmentation, inducing G2/M cell cycle arrest, overproducing oxidative stress, and decreasing cellular antioxidant levels. These compounds combined with cisplatin caused upregulation in the pro-apoptotic Bax, Bid, caspase-3, caspase-8, caspase-9, Fas, and p53 gene expressions while downregulating anti-apoptotic DFFA, NFkB1, and Bcl2 gene expressions. These combinations caused vascular loss and a reduction in VEGF expression. CONCLUSION: These results suggest that a combinational regimen of coumarin compounds with cisplatin could enhance the effect of cisplatin in A549 cells. Besides, these compounds exhibit relatively low toxicity in normal cells, thus decreasing the dose requirement of cisplatin in cancer treatments.

Newly Synthesized Benzimidazoles Inhibit Vascular Endothelial Growth Factor and Matrix Metalloproteinase-2 and -9 Levels in Prostate Cancer Cells.

BACKGROUND: Investigating the effects of newly synthesized agents on various molecular mechanisms to understand their mechanism of action is an important step of pre-clinical screening. Benzimidazoles are composed of a unique fused benzene and imidazole ring and have attracted great attention due to their broad bioactivities, including antitumor. OBJECTIVE: In the current study, we reported the synthesis of novel benzimidazole derivatives and investigated the possible cytotoxic and anti-angiogenic effects on human prostate cancer and umbilical vein endothelial cells (HUVECs). METHODS: MTT assay was used to assess cell viability. A scratch assay was conducted to monitor the migration of cells. mRNA expression levels of VEGF, MMP-2, and MMP-9 were evaluated using qPCR. Changes in protein levels were evaluated by western blotting. RESULTS: Compound G1, having a chlorine moiety, showed a potent cytotoxic activity on both prostate cancer cells and HUVECs, and inhibited cell migration via decreasing the mRNA and protein levels of key angiogenesis-related molecules such as VEGF, MMP-2, and MMP-9. CONCLUSION: These results suggest that newly synthesized G1 may be a novel anti-angiogenic agent for prostate cancer treatment.

Synthesis and anticancer activities of some new coumarin derivatives including the triazole ring and their in silico molecular docking studies.

The synthesis, docking study, and investigation of the anticancer activities of some coumarin derivatives containing the triazole ring are reported in this study. The newly synthesized compounds were screened for their in vitro anticancer activity against the cell lines CRL5807 (human bronchioalveolar carcinoma), CRL5826 (human squamous cell carcinoma), MDA-MB231 (human breast cancer cells), HTB177 (human lung cancer), PC-3 (human prostate adenocarcinoma), PANC-1 (human pancreatic cancer cells), used as cancer cells, and CCD34Lu (normal human lung fibroblasts), used as a healthy cell line. Cytotoxicity effects of the samples were determined by the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay. In silico studies were also performed to explore the binding interactions of the molecules.

Novel benzimidazole derivatives: Synthesis, in vitro cytotoxicity, apoptosis and cell cycle studies.

The aim of the study was to synthesize a new series of benzimidazole derivatives and to investigate the underlying molecular mechanisms of the potential cell cycle inhibition and apoptotic effects against a panel of selected human cancer cell lines along with HEK-293 human embryonic kidney cells. MTT assay was used to evaluate cytotoxic effects. Muse™ Cell Analyzer was used to assess cell cycle progression. Annexin-V/PI staining assay was used for detecting apoptosis. All the synthesized compounds showed a significant cytotoxic effect against cancer cells with the IC50 values between 9.2 and 166.1 µg/mL. Among the tested derivatives, compound 5 showed significant cytotoxic activity against MCF-7, DU-145 and H69AR cancer cells with the IC50 values of 17.8 ± 0.24, 10.2 ± 1.4 and 49.9 ± 0.22 µg/mL respectively. The compounds 5 was also tested on HEK-293 human embryonic kidney cells and found to be safer with lesser cytotoxicity. The results revealed that compound 5 significantly increased cell population in the G2/M-phase which is modulated by a p53 independent mechanism. Compound 5 caused an increase in the percentage of late apoptotic cells in all tested cancer cells in a concentration-dependent manner. Among all synthesized derivatives, compound 5 the bromo-derivative, showed the highest cytotoxic potential, induced G2/M cell cycle arrest and apoptotic cell death in genotypically different human cancer cells. These results suggest that compound 5 might be a promising agent for cancer therapy and further structural modifications of benzimidazole derivatives may create promising anticancer agents.

Ameliorative effect of edible Halopteris scoparia against cadmium-induced reproductive toxicity in male mice: A biochemical and histopathologic study.

Cadmium (Cd) is a toxic metal affecting the reproductive system. Halopteris scoparia (brown algae) is generally consumed as a salad in the Far East countries. This study was conducted to compare and determine the possible protective effects of H. scoparia and vitamin E and C combination (VEC) against cadmium chloride (CdCl2 )-induced reproductive toxicity. A total of 36 male mice were equally divided into as control, CdCl2 (2 mg/kg), CdCl2  + H. scoparia (900 mg/kg), CdCl2  + VEC (200 mg/kg), H. scoparia alone and VEC alone groups. Blood and testis samples were taken for biochemical, histochemical and immunohistochemical analyses. H. scoparia was also examined for antioxidant activity (by DPPH assay) and mineral/trace element content (by ICP-MS method). CdCl2 exposure caused a significant deterioration in body weight, sperm parameters (count, motility, viability and morphology) (p < .001), histopathology, immunoreactivity and testosterone levels. However, H. scoparia improved CdCl2 -induced deterioration effects more successfully than VEC-treated group. The present study suggests that edible H. scoparia can be used as a natural protective agent against Cd-induced testicular damage by possibly enhancing essential element levels or increasing antioxidant defence system.

Apoptosis-inducing activities of Halopteris scoparia L. Sauvageau (Brown algae) on cancer cells and its biosafety and antioxidant properties.

The aim of this study was to reveal the biological activities and in vivo toxicity profiles of n-hexane, chloroform and methanol extracts of brown algae Halopteris scoparia L. Sauvageau. In this study, extracts were tested for their phytochemical contents and antioxidant activities. The cytotoxic activities of the extracts against cervical adenocarcinoma (HeLa), colon colorectal adenocarcinoma (CaCo-2) and breast adenocarcinoma (MCF7) cells were assessed by MTT assay and total RNAs derived from cell lines to analyze gene expression were analyzed by Real Time Ready Human Apoptosis Panel 96. Also, in vivo toxicity and irritation effects of extracts were evaluated by LD50 acute toxicity test and Hen's egg test chorioallantoic membrane (HET-CAM) assay, respectively. Our results showed that the phenolic and flavonoid contents were determined only in methanol extract (33.20 ± 1.41 mg GAE/g and 1.26 ± 0.95 mg QE/g). Also, n-hexane has a broader spectrum of content than methanol and chloroform extracts. Furthermore, n-hexane extract in DPPH and methanol extract in ABTS+ exhibited the best antioxidant activity. In addition, MTT results revealed that each three extracts cause a significant reduction in cell viability, especially in HeLa cells. When the apoptotic gene expressions were examined after treatment of extracts, the expression of many pro-apoptotic genes in both caspase-independent and caspase-dependent intrinsic and extrinsic pathways increased. These findings suggest that, considering that it had not led to irritation and toxicity in vivo, edible H. scoparia is a natural antioxidant and its apoptotic/cytotoxic activities can potentially be used against human cancers.

Multi-Biomarker Responses After Exposure to Pollution in the Mediterranean Mussels (Mytilus galloprovincialis L.) in the Aegean Coast of Turkey.

In this study, sublethal effects on the Mediterranean mussels (Mytilus galloprovincialis L.) collected from the Aegean coast of Turkey were determined. Enzymes such as glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and acetylcholinesterase (AChE), metallothionein (MT) mRNA expressions, thiobarbituric acid reactive substances (TBARS) contents, determination of 14 heavy metals and micronucleus frequency were selected as multibiomarkers. Results show that heavy metals and an increase in the level of MT gene expression have been determined in tissues of mussels collected from all stations. The GST, SOD and CAT enzymes were increased in mussels of Aliaga and Old Foca, compared to the mussels of Urla, while it was showed inhibition at AChE levels. Extensive LP is determined on mussels of Aliaga. It was determined that mussels in Aliaga region have exposed more oxidative stress than Old Foca and Urla. These biomarkers were carried out for the first time in these stations to assess environmental quality.

Histopathological and apoptotic changes on marine mussels Mytilus galloprovincialis (Lamark, 1819) following exposure to environmental pollutants.

Marine bivalve mussels, especially Mytilus species are an earlywarning system used for determining of damage caused by the various aquatic pollutions. In the present study, Mytilus galloprovincialis L. (black mussel) have been utilised as a biomonitoring organism to reveal environmental pollution in the Aliaga, Foca and Urla where located along the Izmir Coast of Turkey. Mussels were collected at these areas and gill and hepatopancreas (digestive gland) tissues were excised. mRNA expressions of initiator (caspase-2 and -8) and executioner (caspase -3/7-1, -3/7-2, -3/7-3 and -3/7-4) caspases of mussels tissues in areas exposed to pollution agent have been observed. TUNEL immunoreactivity in paralel to histopathological changes in both Aliaga and Foca areas were compared with Urla. This study is the first report to reveal the pollution with apoptotic expression on mussels in the coast of Turkey.

Antimicrobial and antioxidant activities with acute toxicity, cytotoxicity and mutagenicity of Cystoseira compressa (Esper) Gerloff & Nizamuddin from the coast of Urla (Izmir, Turkey).

The aim of the study was to evaluate the biological activities with toxic properties of the methanol, hexane, and chloroform extracts of Cystoseira compressa (Esper) Gerloff & Nizamuddin from the Coast of Urla in the Aegean Sea. The extracts of C. compressa were tested for their antimicrobial and antioxidant activities in this study. Cytotoxic and mutagenic potentials of the extracts were also evaluated using cell culture and mutagenicity assays. Hexane extract was found to have higher total flavonoid and phenolic contents than the other extracts and exerted higher antioxidant activity than other extracts. All extracts exhibited moderate antimicrobial activity against tested microorganisms (minimum inhibitory concentration ranges are 32-256 µg/mL). The results indicated that the extracts had no significant cytotoxic activity against human hepatocellular carcinoma Hep 3B cell line in all treated concentrations (5-50 µg/mL) and did not show mutagenicity in the Ames test. Lethality was not observed among mice treated with oral doses of the extracts. In conclusion, results of investigations indicate that brown alga C. compressa is a natural source of antioxidant. It has moderate antimicrobial activities with no toxicity.

The cytogenetic effects of the aqueous extracts of migratory locust (Locusta migratoria L.) in vitro.

One of the useful and most commonly cultivated commercially species, migratory locust (Locusta migratoria; Orthoptera), was investigated in light of genotoxic damage potentials. For this aim, we evaluated the genotoxic potentials of water soluble extracts of L. migratoria on cultured human blood cells. The micronucleus, sister chromatid exchange and structural chromosome aberration assays were applied to assess DNA and chromosomal damage produced by aqueous extracts in vitro. The extracts were added to the cultures at different concentrations ranging from 0 to 1000 mg/L. Our results indicated that these extracts did not exhibit genotoxicity at tested concentrations. We conclude that this in vitro approach for biomonitoring genotoxicity assessment is useful for comparing the potential health risks of edible insects.