Effect of gamma-ray irradiated reduced graphene oxide (rGO) on environmental health: An in-vitro and in-vivo studies.

The unique properties of reduced graphene oxide (rGO) have drawn the attention of scientists worldwide since the last decade and it is explored for a wide range of applications. However, the rapid expansion of rGO use in various products will eventually lead to environenal exposure and rises a safety concern on the environment and humal health risk. Moreover, the utilization of toxic chemicals for the reduction of graphene oxide (GO) into rGO is not environmentally friendly, warranting the exploration of non-toxic approaches. In the present work, rGO was synthesized using a different dose of gamma-ray irradiation and characterized. The in-vitro and in-vivo analysis indicated that the gamma-irradiated rGO induced toxicity depending on its degree of reduction and dosage. In the L929 cells, rGO-30 KGy significantly induced cytotoxicity even at low concentration (1 mg L-1) by inducing reactive oxygen species (ROS), lactate dehydrogenase (LDH) enzyme production, nuclear fragmentation and apoptosis. The change in morphology of the cells like membrane blebbing and cell rounding was also observed via FESEM. In the in-vivo model Caenorhabditis elegans, rGO-30 KGy significantly affected the functioning of primary and secondary targeted organs and also negatively influenced the nuclear accumulation of transcription factors (DAF-16/FOXO and SKN-1/Nrf2), neuronal health, and antioxidant defense mechanism of the nematodes. The real-time PCR analysis showed significant up-regulation (ced-3, ced-4, cep-1, egl-1, and hus-1) and down-regulation (ced-9) of the gene involved in germ-line and DNA damage-induced apoptosis. The detailed toxicity mechanism of gamma irradiated rGO has been elucidated. This work highlights the toxicity of rGO prepared by gamma-ray radiation and paves way for understating the toxicity mechanism.

Dual sensing of methionine and aspartic acid in aqueous medium by a quinoline-based fluorescent probe.

A quinoline-based Schiff base sensor, 6-methyl-2-oxo-1,2-dihydro-quinoline-3-carboxaldehyde-4(N)-phenylsemicarbazone (6MPS), has been developed for selective sensing of methionine and aspartic acid in aqueous medium through "on-off-on" type selective detection of copper ion. Fluorescence imaging of 6MPS, 6MPSC, 6MPSCN, 6MPSC-met, 6MPSCN-met, 6MPSC-asp and 6MPSCN-asp has been successfully demonstrated, in which the sensing probes 6MPSC-met, 6MPSCN-met, 6MPSC-asp and 6MPSCN-asp displayed bright green fluorescence in both in vitro and in vivo live cells.

Engineering the surface of graphene oxide with bovine serum albumin for improved biocompatibility in Caenorhabditis elegans.

Graphene oxide (GO) has been extensively studied for its potential biomedical applications. However, its potential risk associated with the interactions of GO in a biological system hampers its biomedical applications. Therefore, there is an urgent need to enhance the biocompatibility of GO. In the present study, we decorated the surface of GO with bovine serum albumin (GO-BSA) to mitigate the in vivo toxic properties of GO. An in vivo model Caenorhabditis elegans has been used to study the potential protective effect of BSA decoration in mitigating GO induced toxicity. The BSA decoration on the surface of GO prevents the acute and prolonged toxicity induced by GO in primary and secondary organs by maintaining normal intestinal permeability, defecation behavior, development, and reproduction. Notably, GO-BSA treatment at 0.5-100 mg L-1 does not affect the intracellular redox status and lifespan of C. elegans. Reporter gene expression analysis revealed that exposure to GO-BSA (100 mg L-1) did not significantly influence the nuclear accumulation and expression patterns of DAF-16/FOXO and SKN-1/Nrf2 transcription factors and their downstream target genes sod-3, hsp-16.2, ctl-1,2,3, gcs-1, and gst-4 when compared to exposure to pristine GO. Also, quantitative real-time PCR results showed that GO-BSA did not alter the expression of genes involved in regulating DNA damage checkpoints (cep-1, hus-1 and egl-1) and core signaling pathways of apoptosis (ced-4, ced-3 and ced-9), in contrast to GO treatment. All these findings will have an impact on the future development of safer nanomaterial formulations of graphene and graphene-based materials for environmental and biomedical applications.

Organoruthenium(II) complexes attenuate stress in Caenorhabditis elegans through regulating antioxidant machinery.

The 1:1 stoichiometric reactions of 3-methoxy salicylaldehyde-4(N)-substituted thiosemicarbazones (H2L1-4) with [RuCpCl(PPh3)2] was carried out in methanol. The obtained complexes (1-4) were characterized by analytical, IR, absorption and 1H NMR spectroscopic studies. The structures of ligand [H2-3MSal-etsc] (H2L3) and complex [RuCp(Msal-etsc) (PPh3)] (3), were characterized by single crystal X-ray diffraction studies. The interaction of the ruthenium(II) complexes (1-4) with calfthymus DNA (CT-DNA) has been explored by absorption and emission titration methods. Based on the observations, an intercalative binding mode of DNA has been proposed. The protein binding abilities of the new complexes were monitored by quenching the tryptophan and tyrosine residues of BSA, as model protein. From the studies, it was found that the new ruthenium metallacycles exhibited better affinity than their precursors. The free radical scavenging assay suggests that all complexes effectively scavenged the DPPH radicals as compared to that of standard control ascorbic acid and scavenging activities of complexes are in the order of 4 > 2 > 3 > 1. In addition, ruthenium(II) complexes (2-4) also exhibited an excellent in vivo antioxidant activity as it was able to increase the survival of worms exposed to lethal oxidative and thermal stresses possibly through reducing the intracellular ROS levels. It was interesting to note that complexes 2-4 failed to increase the lifespan of mev-1 mutant worms having shortened lifespan due to the over production of free radicals. This data confirmed that complexes 2-4 conferred stress resistance in C. elegans, but they also require an endogenous detoxification mechanism for doing so. The genetic and reporter gene expression analysis revealed that complexes 2-4 maintained the intracellular redox status and offered stress protection through transactivation of antioxidant defence machinery genes gst-4 and sod-3 which are directly regulated by SKN-1 and DAF-16 transcription factors, respectively. Altogether, our results suggested that complexes 2-4 might play a crucial role in stress modulation and they perhaps exert almost similar effects in higher models, which is an important issue to be validated in future.

East Indian sandalwood (Santalum album L.) oil confers neuroprotection and geroprotection in Caenorhabditis elegans via activating SKN-1/Nrf2 signaling pathway.

East Indian Sandalwood Oil (EISO) has diverse beneficial effects and has been used for thousands of years in traditional folk-medicine for treatment of different human ailments. However, there has been no in-depth scientific investigation to decipher the neuroprotective and geroprotective mechanism of EISO and its principle components, α- and ß-santalol. Hence the current study was undertaken to assess the protective effects of EISO, and α- and ß-santalol against neurotoxic (6-OHDA/6-hydroxydopamine) and proteotoxic (α-synuclein) stresses in a Caenorhabditis elegans model. Initially, we found that EISO and its principle components exerted an excellent antioxidant and antiapoptotic activity as it was able to extend the lifespan, and inhibit the ROS generation, and germline cell apoptosis in 6-OHDA-intoxicated C. elegans. Further, we showed that supplementation of EISO, and α- and ß-santalol reduced the 6-OHDA and α-synuclein-induced Parkinson's disease associated pathologies and improved the physiological functions. The genetic and reporter gene expression analysis revealed that an EISO, or α- and ß-santalol-mediated protective effect does not appear to rely on DAF-2/DAF-16, but selectively regulates SKN-1 and its downstream targets involved in antioxidant defense and geroprotective processes. Together, our findings indicated that EISO and its principle components are worth exploring further as a candidate redox-based neuroprotectant for the prevention and management of age-related neurological disorders.

Organoruthenium(II) Complexes Ameliorates Oxidative Stress and Impedes the Age Associated Deterioration in Caenorhabditis elegans through JNK-1/DAF-16 Signalling.

New ruthenium(II) complexes were synthesised and characterized by various spectro analytical techniques. The structure of the complexes 3 and 4 has been confirmed by X-ray crystallography. The complexes were subjected to study their anti-oxidant profile and were exhibited significantly greater in vitro DPPH radical scavenging activity than vitamin C. We found that complexes 1-4 confered tolerance to oxidative stress and extend the mean lifespan of mev-1 mutant worms and wild-type Caenorhabditis elegans. Further, mechanistic study and reporter gene expression analysis revealed that Ru(ƞ6-p-cymene) complexes maintained the intracellular redox status and offers stress resistance through activating JNK-1/DAF-16 signaling axis and possibly by other antioxidant response pathway. Notably, complex 3 and 4 ameliorates the polyQ (a Huntington's disease associated protein) mediated proteotoxicity and related behavioural deficits in Huntington's disease models of C. elegans. From these observations, we hope that new Ru(ƞ6-p-cymene) complexes could be further considered as a potential drug to retard aging and age-related neurodegenerative diseases.