The present study was designed to investigate genotoxic and cytotoxic effects and oxidative damage of increasing concentrations of nano-hydroxyapatite (5, 10, 20, 50, 75, 100, 150, 300, 500 and 1000 ppm) in primary human blood cell cultures. Cell viability was detected by [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] assay and lactate dehydrogenase release, while total antioxidant capacity and total oxidative stress levels were determined to evaluate the oxidative injury. The DNA damage was also analyzed by sister chromatid exchange, micronuclei, chromosome aberration assays and 8-oxo-2-deoxyguanosine level as indicators of genotoxicity. The results of [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] and lactate dehydrogenase assays showed that the higher concentrations (150, 300, 500 and 1000 ppm) of hydroxyapatite nanoparticles (HAP NPs) decreased cell viability. HAP NPs led to increases of total oxidative stress (300, 500 and 1000 ppm) levels and decreased total antioxidant capacity (150, 300, 500 and 1000 ppm) levels in cultured human blood cells. On the basis of increasing concentrations, HAP NPs caused significant increases of sister chromatid exchange, micronuclei, chromosome aberration rates and 8-oxo-2-deoxyguanosine levels as compared to untreated culture. In conclusion, the obtained in vitro results showed that HAP NPs had dose-dependent effects on inducing oxidative damage, genotoxicity and cytotoxicity in human blood cells.

Context Since methods utilised in the treatment of glioblastoma multiforme (GBM) are inadequate and have too many side effects, usage of herbal products in the treatment process comes into prominence. Lichens are symbiotic organisms used for medicinal purposes for many years. There are various anticancer treatments about components of two lichen species used in the present study. Objective Antitumor potential of three lichen secondary metabolites including olivetoric acid (OLA) and physodic acid (PHA) isolated from Pseudevernia furfuracea (L.) Zopf (Parmeliaceae) and psoromic acid (PSA) isolated from Rhizoplaca melanophthalma (DC.) Leuckert (Lecanoraceae) were investigated on human U87MG-GBM cell lines and primary rat cerebral cortex (PRCC) cells for the first time. Materials and methods PRCC cells used as healthy brain cells were obtained from SpragueDawley rats. The treatments were carried out on the cells cultured for 48 h. Cytotoxic effects of different concentrations (2.5, 5, 10, 20 and 40 mg/L) of metabolites on the cells were determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) analyses. Total antioxidant capacity (TAC) and total oxidant status (TOS) parameters were used for assessing oxidative alterations. Oxidative DNA damage potentials of metabolites were investigated via evaluating 8-hydroxy-2 0 -deoxyguanosine (8-OH-dG) levels. Results Median inhibitory concentration (IC 50 ) values of OLA, PHA and PSA were 125.71, 698.19 and 79.40 mg/L for PRCC cells and 17.55, 410.72 and 56.22 mg/L for U87MG cells, respectively. It was revealed that cytotoxic effects of these metabolites showed positive correlation with concentration, LDH activity and oxidative DNA damage. Discussion and conclusion The present findings obtained in this study revealed that primarily OLA and then PSA had high potential for use in the treatment of GBM. ARTICLE HISTORY

Olanzapine (OLZ) is an atypical antipsychotic drug and is commonly used for the treatment of schizophrenia and bipolar disorder (BD). However, recent reports indicated that this drug could exhibit cytotoxic effects on nervous and immune systems. To our knowledge, there is scarce data considering the genotoxic or oxidative damage potentials of OLZ on human lymphocyte culture system. Therefore, in this study, the genotoxic potential of OLZ (0 to 160 µM) have been evaluated in human whole blood cultures (WBCs) related to oxidative status. Sister-chromatid exchange (SCE) test was applied to estimate the DNA damage, and biochemical parameters (total antioxidant capacity [TAC] and total oxidative stress [TOS]) were examined to determine oxidative stress. Our results indicated that the tested antipsychotic drug did not induce SCEs in lymphocytes of treated cultures. However, the application of the highest OLZ concentration caused oxidative stress. It is concluded that the OLZ can be used safely, but it is necessary to consider the tissue damages that are likely to appear depending on the oxidative stress.

Paclitaxel (PAC) and cisplatin (CIS) are two established chemotherapeutic drugs used in combination for the treatment of various solid tumors. However, the usage of PAC and CIS are limited because of the incidence of their moderate or severe neurotoxic side effects. In this study, we aimed to assess the protective role of salicylic acid (SA) against neurotoxicity caused by PAC and CIS. For this purpose, newborn Sprague Dawley rats were decapitated in sterile atmosphere and primary cortex neuron cultures were established. On the 10th day SA was added into culture plates. PAC and CIS were added on the 12th day. The cytotoxicity was determined by using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Oxidative alterations were assessed using total antioxidant capacity and total oxidative stress assays in rat primary neuron cell cultures. It was shown that both concentrations of PAC and CIS treatments caused neurotoxicity. Although SA decreased the neurotoxicity by CIS and PAC, it was more effective against the toxicity caused by CIS rather than the toxicity caused by PAC. In conclusion it was clearly revealed that SA decreased the neurotoxic effect of CIS and PAC in vitro.

In this study, the cytotoxic, genotoxic/ antigenotoxic and antioxidant/oxidant activity of copaene (COP), a plant-derived tricyclic sesquiterpene, on human lymphocyte cultures (n = 5) was investigated. COP was added into culture tubes at various concentrations (0, 10, 25, 50, 100, 200 and 400 mg/L). While the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays were used for viability and cytotoxic evaluations, the micronucleus (MN) and sister chromatid exchange (SCE) assays were used for genetic evaluations. Moreover, total antioxidant capacity (TAC) and total oxidative status analysis were used for biochemical evaluations. According to LDH and MTT assays COP significantly reduced cell proliferation at high concentrations (200 and 400 mg/ L). In addition, there was no significant increase (P \ 0.05) in both SCE and MN frequencies of cultures treated with COP as compared to controls. We have also concluded that concentrations of COP of 50 and 100 mg/L increased TAC level when compared to the controls. In conclusion, in this study it has been reported for the first time that copaene is not genotoxic and it increases the antioxidant capacity in human lymphocyte cultures.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent and ubiquitous environmental contaminant. The health impact of TCDD exposure is of great concern to the general public. Recent reports have implied that eicosapentaenoic acid (EPA) might be a potential chemopreventive agent and influence hepatotoxicity. The aim of the current study was to explore the effectiveness of EPA in alleviating the toxicity of TCDD on primary cultured rat hepatocytes. EPA (5, 10 and 20 lM) was added to cultures alone or simultaneously with TCDD (5 and 10 lM). Rat hepatocytes were treated with TCDD and EPA for 48 h, and then cytotoxicity was detected by [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT) assay and lactate dehydrogenase (LDH) release, while total antioxidant capacity (TAC) and total oxidative stress (TOS) levels were determined to evaluate the oxidative injury. The DNA damage was also analyzed by liver micronucleus assay (LMN) and 8-oxo-2-deoxyguanosine (8-OH-dG). The results of MTT and LDH assays showed that TCDD but not EPA decreased cell viability. TCDD also increased TOS level and significantly decreased TAC level in rat hepatocytes in a clear dose dependent manner. On the basis of increasing doses, the dioxin caused significant increases of micronucleated hepatocytes (MNHEPs) and 8-OH-dG as compared to control culture. Whereas, in cultures treated with EPA alone, TOS level did not change and the level of TAC significantly increased. The presence of EPA with TCDD minimized the toxic effects of the dioxin on primary hepatocytes cultures. Noteworthy, EPA has a protective effect against TCDD-mediated DNA damages.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces hepatic damage. Propolis exhibits antioxidant properties and several studies suggest that supplementations with antioxidants can influence hepatotoxicity. Therefore, the aim of the current study was to explore the effectiveness of propolis in alleviating the toxicity of TCDD in the liver of rats. Animals were divided into six groups, namely, TCDD (0.75 and 8 µg/kg body weight (bw)), propolis (50 mg/kg bw), TCDD (0.75 and 8 µg) plus propolis (50 mg/kg bw), and control, respectively. Rats were intraperitoneally administered with their respective doses daily for 21 days. In rats that received a high dose of TCDD, the antioxidant enzymes were significantly decreased and the serious pathological findings were established. Also, the rate of hepatocyte micronucleus (HMN) was increased after treating with TCDD. The reactions of enzymes in control and low-dose group were weak. The frequencies of HMN and liver histology were similar to both the groups. The presence of propolis with TCDD alleviated its pathological effects in hepatic tissue. Propolis also prevented the suppression of antioxidant enzymes in the livers of animals exposed to TCDD and displayed a strong protective effect against HMN. It can be concluded that propolis has beneficial influences and was able to antagonize TCDD toxicity in the liver.

Alpha-copaene (α-COP), a tricyclic sesquiterpene, is present in several essential oils of medicinal and aromatic plants and has antioxidant and antigenotoxic features. Its cytotoxic, cytogenetic and oxidative effects have not been investigated in neuron and N2a neuroblastoma (NB) cell cultures. Therefore, we aimed to describe in vitro: (i) cytotoxic properties by 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenlytetrazolium bromide test; (ii) antioxidant/oxidant activity by total antioxidant capacity (TAC) and total oxidative status (TOS) analysis; and (iii) genotoxic damage potential by single cell gel electrophoresis -of α-COP in healthy neuron and N2a-NB cell cultures for the first time. Significant (P < 0.05) decrease in cell proliferation were observed in cultured primary rat neurons starting with the concentration of 150 mg/L and in N2a-NB cells starting with 100 mg/L. In addition, 25 mg/L of α-COP treatment caused increase of TAC levels and α-COP treatments at higher doses led to increase of TOS levels in neuron N2a-NB cell cultures. Moreover, none of the tested concentrations of α-COP have shown a genotoxic effect on both cell lines. Our findings clearly demonstrate that α-COP exhibited mild cytotoxic effects on N2a-NB cell line. In conclusion, α-COP may have potential as an anticancer agent, which needs to be further studied.