Assessment of Human Health Impacts from Invasive Pufferfish (Attacks, Poisonings and Fatalities) across the Eastern Mediterranean.

The silver-cheeked toadfish Lagocephalus sceleratus (Gmelin 1789), and to a lesser degree the orange spotted toadfish Torquigener hypselogeneion (Bleeker, 1852), pose threats to human health from physical attacks and poisonings in the Eastern Mediterranean Sea. This study reviewed human health-related impacts resulting from these pufferfish, compiling and assessing records from online sources, the peer-reviewed literature, medical records, personal interviews, and observations across the Eastern Mediterranean in the years 2004 to 2023. A total of 198 events impacting human health were documented: 28 records of physical attacks, at least 144 non-lethal poisoning episodes, and 27 human fatalities resulting from consumption. The majority of the reported incidences occurred in Syria, Türkiye, and Lebanon. Most physical attacks occurred in summer, while most poisoning events occurred during winter. The number of recorded incidents greatly increased after 2019, especially with regard to poisonings, yet whether this is related to greater media attention, or to increased fish abundance is unclear. This is the first comprehensive study to collate findings on attacks, poisonings and fatalities caused by these pufferfish in the Mediterranean Sea, and may help in improving national health policies. We urge the continuation of national campaigns to caution residents and tourists of these species' high toxicities and potential aggressiveness.

Holospiniferoside: A New Antitumor Cerebroside from The Red Sea Cucumber Holothuria spinifera: In Vitro and In Silico Studies.

Chemical investigation of the methanolic extract of the Red Sea cucumber Holothuria spinifera led to the isolation of a new cerebroside, holospiniferoside (1), together with thymidine (2), methyl-α-d-glucopyranoside (3), a new triacylglycerol (4), and cholesterol (5). Their chemical structures were established by NMR and mass spectrometric analysis, including gas chromatography-mass spectrometry (GC-MS) and high-resolution mass spectrometry (HRMS). All the isolated compounds are reported in this species for the first time. Moreover, compound 1 exhibited promising in vitro antiproliferative effect on the human breast cancer cell line (MCF-7) with IC50 of 20.6 µM compared to the IC50 of 15.3 µM for the drug cisplatin. To predict the possible mechanism underlying the cytotoxicity of compound 1, a docking study was performed to elucidate its binding interactions with the active site of the protein Mdm2-p53. Compound 1 displayed an apoptotic activity via strong interaction with the active site of the target protein. This study highlights the importance of marine natural products in the design of new anticancer agents.

Sarcophine and (7S, 8R)-dihydroxydeepoxysarcophine from the Red Sea soft coral Sarcophyton glaucum as in vitro and in vivo modulators of glycine receptors.

The inhibitory glycine receptor (GlyR) is a key mediator of synaptic signalling in spinal cord, brain stem, and higher centres of the central nervous system. We examined the glycinergic activity of sarcophine (SN), a marine terpenoid known for its various biological activities, and its trans-diol derivative (7S, 8R)-dihydroxy-deepoxysarcophine (DSN). SN was isolated from the Red Sea soft coral Sacrophyton glaucum, DSN was semisynthesized by hydrolysis of the epoxide ring. In cytotoxicity tests against HEK293 cells, SN and DSN had LD50 values of 29.3 ± 3.0 mM and 123.5 ± 13.0 mM, respectively. Both compounds were tested against recombinant human α1 glycine receptors in HEK293 cells using whole-cell recording techniques. Both, SN and DSN were shown for the first time to be inhibitors of recombinant glycine receptors, with KIvalues of 2.1 ± 0.3 µM for SN, and 109 ± 9 µM for DSN. Receptor inhibition was also studied in vivo in a mouse model of strychnine toxicity. Surprisingly, in mouse experiments strychnine inhibition was not augmented by either terpenoid. While DSN had no significant effect on strychnine toxicity, SN even delayed strychnine effects. This could be accounted for by assuming that strychnine and sarcophine derivatives compete for the same binding site on the receptor, so the less toxic sarcophine can prevent strychnine from binding. The combination of modulatory activity and low level of toxicity makes sarcophines attractive structures for novel glycinergic drugs.

Spectroscopic analyses and genotoxicity of dioxins in the aquatic environment of Alexandria.

Dioxins have global concerns because of the bioaccumulation tendency and persistency in the environment. Water, seabream Pagrus auratus and seabass Dicentrarchus labrax samples were collected from Abu Qir, Alexandria to evaluate the concentration of dioxin. Fourier Transform Infrared Spectrometer (FTIR) and molecular modeling was applied for elucidating the molecular structure of fish samples. Furthermore, HPLC with UV detection was used to determine the concentration of dioxins (2,8-dichloro dibenzo-p-dioxin). RT-PCR assay was conducted to verify the expression of some immune genes in the fish species as a result of water pollution. The average detected concentrations varied from 0.2 to 1.3µg/l. Gene expression revealed that MHC class 1 and C3 were highly upregulated in liver and muscle of seabass and seabream while T2BP was highly regulated in seabass liver and seabream muscle and seabass muscle for transferrin, FTIR and molecular modeling indicate that dioxin finds its way to fish protein.

A pyridinium derivative from Red Sea soft corals inhibited voltage-activated potassium conductances and increased excitability of rat cultured sensory neurones.

BACKGROUND: Whole cell patch clamp recording and intracellular Ca2+ imaging were carried out on rat cultured dorsal root ganglion (DRG) neurones to characterize the actions of crude extracts and purified samples from Red Sea soft corals. The aim of the project was to identify compounds that would alter the excitability of DRG neurones. RESULTS: Crude extracts of Sarcophyton glaucum and Lobophyton crassum attenuated spike frequency adaptation causing DRG neurones to switch from firing single action potentials to multiple firing. The increase in excitability was associated with enhanced KCl-evoked Ca2+ influx. The mechanism of action of the natural products in the samples from the soft corals involved inhibition of voltage-activated K+ currents. An active component of the crude marine samples was identified as 3-carboxy-1-methyl pyridinium (trigonelline). Application of synthetic 3-carboxy-1-methyl pyridinium at high concentration (0.1 mM) also induced multiple firing and reduced voltage-activated K+ current. The changes in excitability of DRG neurones induced by 3-carboxy-1-methyl pyridinium suggest that this compound contributes to the bioactivity produced by the crude extracts from two soft corals. CONCLUSION: Sarcophyton glaucum and Lobophyton crassum contain natural products including 3-carboxy-1-methyl pyridinium that increase the excitability of DRG neurones. We speculate that in addition to developmental control and osmoregulation these compounds may contribute to chemical defenses.