Volume 11 (2018): Issue 3 (October 2018)

Sertraline (SRT) is an antidepressant agent used as a neuronal selective serotonin-reuptake inhibitor (SSRI). SRT blocks serotonin reuptake and increases serotonin stimulation of somatodendritic serotonin 1A receptor (5-HT1AR) and terminal autoreceptors in the brain. In the present study, the genotoxic potential of SRT was evaluated using cytokinesis-block micronucleus (CBMN) cytome assay in peripheral blood lymphocytes of healthy human subjects. DNA cleavage-protective effects of SRT were analyzed on plasmid pBR322. In addition, biochemical parameters of total oxidant status (TOS) and total antioxidant status (TAS) in blood plasma were measured to quantitate oxidative stress. Human peripheral blood lymphocytes were exposed to four different concentrations (1.25, 2.5, 3.75 and 5 µg/mL) of SRT for 24- or 48-h treatment periods. In this study, SRT was not found to induce MN formation either in 24- or 48-h treatment periods. In contrast, SRT concentration-dependently decreased the percentage of MN and MNBN (r=−0.979, p<0.01; r=−0.930, p<0.05, respectively) when it was present for the last 48 hr (48-h treatment) of the culture period. SRT neither demonstrated a cleavage activity on plasmid DNA nor conferred DNA protection against H₂O₂. The application of various concentrations of SRT significantly increased the TOS and oxidative stress index (OSI) in human peripheral blood lymphocytes for both the 24- and 48-h treatment periods. Morover, the increase in TOS was potent as the positive control MMC at both treatment times. However, SRT did not alter the TAS levels in either 24- or 48-h treatment periods when compared to control. In addition, exposing cells to SRT caused significant decreases in the nuclear division index at 1.25, 2.50 and 3.75 µg/mL in the 24-h and at the highest concentration (5 µg/mL) in the 48-h treatment periods. Our results suggest that SRT may have cytotoxic effect via oxidative stress on cultured human peripheral blood lymphocytes.

In the present study we investigated the in vitro hepatotoxicity of a set of rhodamine-labelled 3-hydroxy-4-pyridinones (3,4-HPO) that had previously demonstrated significant inhibitory effect in the intramacrophagic growth of Mycobacterium avium. Our aim was to establish a correspondence between the molecular structure and the in vitro toxicological activity of these compounds.

The impact of a set of bidentate (MRB2, MRB7, MRB8, and MRB9) and hexadentate (MRH7, MRH8, and MRH10) chelators on cellular metabolic competence and membrane integrity was investigated in HepG2 cells.

Our findings indicate that: a) hexadentate chelators are more cytotoxic than parent bidentate ligands; b) disruption of cell membrane and metabolic competence only occurred after 5 days, at the highest concentrations tested; c) strict correlation between bacteriostatic activity and in vitro toxicity was observed, which seems to be directly dependent on the size of the molecule and on the hydrophilic/lipophilic balance; d) among the set of bidentate ligands, carboxyrhodamine derivatives (amide linker) presented lower detrimental effects, when compared with rhodamine B isothiocyanate chelators (thiourea linker); e) contrarily, for the hexadentate series, rhodamine B isothiocyanate derivatives are less cytotoxic to HepG2 cells than carboxyrhodamine molecules; and f) for all compounds tested, when the substituents of the nitrogen atom were switched from ethyl to methyl, an increment of toxicity was observed.

Overall, all chelators seem to display suitable in vitro toxicological potential to combat fast grow bacteria. According to their in vitro pharmacological: toxicological potential ratio, MRH7 and MRH8 may be considered as the most suitable compounds to undergo further pre-clinical development studies.

Mustard oil cake is a biofertilizer widely used in agriculture and fish cultivation almost in all South East Asian Countries including India. The study was carried out to observe the effects of this biofertilizer on the liver proteins of Channa punctatus. At sublethal concentration (0.42 g/L ), fishes were exposed for a prolonged period of 35 days and amount of total liver protein (TLP) was measured. The investigation showed a low rate of liver protein synthesis in treated fish after 4 days of exposure. An increase in the amount of protein was observed between the 7^th and 35^th day. But such increment was below the amount of TLP of control fish, indicating physiological stress in the treated fish.

The aim of the research was to determine some basic biological activities of less biomedically studied but commonly known two fungi from the Boletaceae family Suillellus rubrosanguineus and Tylopilus felleus, which grow in the forests of Middle Europe. The cytotoxicity tests of the ethanol and chloroform extracts were carried out using NIH-3T3 and MCF-7 cell lines. The presence of alkaloids in the extracts was assessed by the reaction with Dragendorff reagent. In all of the extracts the positive reaction with the reagent was observed. In general, the extracts from Suillellus rubrosanguineus were more cytotoxic than the extracts from Tylopilus felleus and exhibited no selectivity of activities on healthy and cancer cell lines. However, the extracts from Tylopilus felleus proved to be selectively cytotoxic for cancer cell line. Tylopilus extracts or their isolated bioactive compounds could be considered for further study in pre-clinical experiments.

Bisphenol A is widely used as a material for the production of epoxy resins and polycarbonate plastics. It contaminates various food stuffs by getting leached out from their container lining. Limited information is available on its effects on the male reproductive system. The aim of the present study was to evaluate the extent to which bisphenol A can affect the reproductive system by measuring biochemical and histological changes in the epididymis. Inbred Swiss strain male albino mice were orally administered 80, 120 and 240 mg/kg body weight/day of BPA for 45 days. After completion of treatment, the animals were sacrificed; cauda epididymis was isolated, weighed, used for biochemical and histopathological studies. The results revealed that BPA administered for 45 days caused significant (p<0.05) and dose-dependent reduction in epididymis weight. There was significant (p<0.05) increase in lipid peroxidation and the acid phosphatase activity. Dose dependent reduction in protein, sialic acid contents, as well as the activity of enzymatic antioxidants and mitochondrial enzymes was recorded compared to vehicle treated group. The effect was dose-dependent. Histopathological alteration was observed. This study concludes that BPA causes toxicity in epididymis of mice by generating free radicals, which may be a possible reason for reduction in sperm parameters.

Handling is a form of experience which can result in physiological changes depending on the period of postnatal age when performed. There is a lot of evidence about the positive effect of neonatal handling, but a lack dealing with handling of adult rats. Behavioral changes and memory deficits are present in dementia-like disorders. In the present work, we tested whether 6 weeks lasting handling of young adult rats could revert memory impairment induced by trimethyltin (TMT) (7.5 mg/kg, intraperitoneally). Testing rats in Morris water maze revealed significant effect of TMT as well significant effect of handling. We observed improvement of spatial memory also between healthy, non-degenerated rats as well as degenerated rats, represented by shorter latency onto the platform. In our paper, we report beneficial effect of handling on spatial memory that is in compliance with published works about beneficial effect of cognitive therapy and training in patients with early stage of Alzheimer's disease and dementia.

The objective of the present study was to evaluate the safety of long term consumption of ethanolic fraction of Neurocalyx calycinus leaves (NCEF) in rodents. The NCEF was subjected to detect the presence of various phytoconstituents. In acute oral toxicity study, graded doses of NCEF was administered in mice and were observed up to 14 days. In sub-chronic oral toxicity study, NCEF was administered to Wistar rats at doses of 50, 500 and 1000 mg/kg b.w. per day for 90 days and after that, observed up to 28 days. NCEF showed the presence of alkaloids, steroids, phenolics and glycosides. In acute toxicity study, there was no mortality and no behavioural signs of toxicity at the highest dose level (6400 mg/kg b.w.). In sub-chronic oral toxicity study, there were no significant difference observed in the consumption of food and water, body weight and relative organ weights. Haematological, serum biochemical, hepatic oxidative stress marker analysis and urine analysis revealed the non-adverse effects of prolonged oral consumption of NCEF. The histopatho-logic examination did not show any differences in vital organs. Based on our findings, NCEF, at dosage levels up to 1000 mg/kg b.w., is non-toxic and safe for long term oral consumption.

Soybeans contain the isoflavone aglycone, an endocrine disrupter. To determine the effects of small amounts of isoflavones on developmental processes, we administered 6.25, 62.5, or 625 µg isoflavone per egg to early stage (stage 10) developing chick embryos via the yolk just beneath the embryo. Eggs were kept at 37±0.5 °C and >80% relative humidity, with one rotation per hour for 48 hrs. The embryos were observed under a stereomicroscope for morphological abnormalities and number of somites. Relative to control eggs, there were no significant differences in the average number of somites in eggs administered isoflavone aglycone. Isoflavone, however, had a dose associated effect on abnormal embryogenesis. Embryos treated with isoflavone aglycone showed developmental arrest not reaching somitegenesis, dysmorphology of the neural tube, and shortening of entire embryos.