Lethal and Sub-Lethal Effects and Modulation of Gene Expression Induced by T Kinase Inhibitors in Zebrafish (Danio Rerio) Embryos

Tyrosine kinase inhibitors (TKIs) are designed for targeted cancer therapy. The consumption of these drugs during the last 20 years has been constantly rising. In the zebrafish (Danio rerio) embryo toxicity test, we assessed the toxicity of six TKIs: imatinib mesylate, erlotinib, nilotinib, dasatinib, sorafenib and regorafenib. Imatinib mesylate and dasatinib induced lethal effects, while regorafenib, sorfenib and dasatinib caused a significant increase of sub-lethal effects, predominantly oedema, no blood circulation and formation of blood aggregates. The analyses of the changes in the expression of selected genes associated with the hormone system after the exposure to imatinib mesylate, dasatinib and regorafenib demonstrated that all three tested TKIs deregulated the expression of oestrogen receptor esr1, cytochrome P450 aromatase (cypa19b) and hydroxysteroid-dehydrogenase (hsd3b), regorafenib, and also thyroglobulin (tg). The expression of genes involved in the DNA damage response (gadd45 and mcm6) and apoptosis (bcl2) was deregulated only by exposure to regorafenib. The data indicate that common mechanisms, namely antiangiogenic activity and interference with steroidogenesis are involved in the TKI induced sub-lethal effects and potential hormone disrupting activity, respectively. The residues of TKIs may represent an environmental hazard; therefore, further ecotoxicological studies focusing also on the effects of their mixtures are warranted.

In vivo toxicity of bioreactor-grown biomass and exopolysaccharides from Malaysian tiger milk mushroom mycelium for potential future health applications

Natural mycelial biomass (MB) and exopolysaccharides (EPS) of Malaysian tiger milk mushroom Lignosus rhinocerus are considered high-end components due to their high commercial potential value in drug discovery. This study aims to evaluate the toxicity of the mushroom extracts’ generated in a bioreactor using the zebrafish embryo toxicity (ZFET) model assay as a new therapy for treating asthma. Both MB and EPS extracts, at concentrations 0.16–10 mg/mL, were tested for ZFET and early development effects on Zebrafish Embryos (ZE) during 24–120 h post-fertilisation (HPF). Findings revealed that MB was deemed safe with an LC50 of 0.77 mg/mL; the EPS were non-toxic (LC50 of 0.41 mg/mL). Neither MB nor EPS delayed hatching nor teratogenic defects in the treated ZE at a 2.5 mg/mL dose. There were no significant changes in the ZE heart rate after treatments with MB (130 beats/min) and EPS (140 beats/min), compared to that of normal ZE (120–180 beats/min). Mixing both natural compounds MB and EPS did not affect toxicity using ZFET testing; thus, intimating their safe future use as therapeutic interventions. This represents the first study to have used the ZFET assay on MB and EPS extracts of L. rhinocerus for future health applications.

Embryotoxicity and oxidative stress induced by arsenic in albino mice and protective role of Moringa oleifera

Chronic exposure to arsenic causes the abnormal development of embryo during pregnancy. So the study is designed to investigate the antioxidant and tissue protective properties of Moringa oleifera extracts against sodium arsenate induced embryo toxicity. Moringa oleifera extracts (leaf and flower) were prepared using soxhelt apparatus. Fourty four pregnant females were equally divided in 11 experimental groups (A-K). Group A was of control while B and C were sodium arsenate treated groups as group A (0.00), B (6.00, 0.00), C (12.00, 0.00). Group D to G were of sodium arsenate + Moringa oleifera flower extract treated groups with doses D (6.00, 150.00), E (6.00, 300.00), F (12.00, 150.00), G (12.00, 300.00) and groups H to K were sodium arsenate + Moringa oleifera leaf extracts treated groups H (6.00, 150.00), I (6.00, 300.00), J (12.00, 150.00) and K (12.00, 300.00) mg/kg B.W. Significant (p < 0.05) increased in MDA (malanodialdehyde) values 41.75 ± 3.40 and decreased GSH (glutathione) values 7.75 ± 0.95 in sodium arsenate treated groups were observed as compared to control 25 ± 0.81(MDA) and 18.5 ± 0.57 (GSH). Moringa oleifera extracts treated groups especially Moringa oleifera leaf extract at dose of 300mg/kg B.W normalized the MDA (25.25 ± 0.50) and GSH (18.25 ± 1.70) values. Sodium arsenate induced the histopathologiacl changes like malformed heart, meningocoel, spina bifida, anopathalmia, cavitization, degenerated kidney and intestine. Whereas Moringa oleifera leaf extract as ameliorant minimized these histopathological abnormalities. It is concluded that Moringa oleifera leaf extract is mixture of biomolecules as it has antioxidant activity, so can be used as ameliorant against sodium arsenate.

Impacts of Plastic-Made Packaging on Marine Key Species: Effects Following Water Acidification and Ecological Implications

This study evaluates the impacts of 16 different leachates of plastic-made packaging on marine species of different trophic levels (bacteria, algae, echinoderms). Standard ecotoxicological endpoints (inhibition of bioluminescence, inhibition of growth, embryo-toxicity) and alterations of ecologically significant parameters (i.e., echinoderms’ body-size) were measured following exposure under different pH water conditions: marine standard (pH 8.1) and two increasingly acidic conditions (pH 7.8 and 7.5) in order to evaluate possible variations induced by ocean acidification. The results obtained in this study evidence that the tested doses are not able to significantly affect bacteria (Vibrio fischeri) and algae (Phaeodactylum tricornutum). On the contrary, Paracentrotus lividus larvae were significantly affected by several packaging types (13 out of 16) with meaningless differences between pH conditions.