Dynamin-independent CaV1.2 and KCa1.1 channels regulation and vascular tone modulation by the mitochondrial fission inhibitors dynasore and dyngo-4a

A role for mitochondrial fission in vascular contraction has been proposed based on the vasorelaxant activity of the dynamin (and mitochondrial fission) inhibitors mdivi-1 and dynasore. However, mdivi-1 is capable to inhibit Ba2+ currents through CaV1.2 channels (IBa1.2), stimulate KCa1.1 channel currents (IKCa1.1), and modulate pathways key to the maintenance of vessel active tone in a dynamin-independent manner. Using a multidisci-plinary approach, the present study demonstrates that dynasore, like mdivi-1, is a bi-functional vasodilator, blocking IBa1.2 and stimulating IKCa1.1 in rat tail artery myocytes, as well as promoting relaxation of rat aorta rings pre-contracted by either high K+ or phenylephrine. Conversely, its analogue dyngo-4a, though inhibiting mitochondrial fission triggered by phenylephrine and stimulating IKCa1.1, did not affect IBa1.2 but potentiated both high K+- and phenylephrine-induced contractions. Docking and molecular dynamics simulations identified the molecular basis supporting the different activity of dynasore and dyngo-4a at CaV1.2 and KCa1.1 channels. Mito-tempol only partially counteracted the effects of dynasore and dyngo-4a on phenylephrine-induced tone. In conclusion, the present data, along with previous observations (Ahmed et al., 2022) rise caution for the use of dynasore, mdivi-1, and dyngo-4a as tools to investigate the role of mitochondrial fission in vascular contraction: to this end, a selective dynamin inhibitor and/or a different experimental approach are needed

Nutritionally enriched tomatoes (Solanum lycopersicum L.) grown with wood distillate: chemical and biological characterization for quality assessment

: Bio-based products are nowadays useful tools able to affect the productivity and quality of conventionally cultivated crops. Several bio-based products are currently on the market; one of the newest and most promising is the wood distillate (WD) derived from the pyrolysis process of waste biomass after timber. Its foliar application has been widely investigated and shown to promote the antioxidant profile of cultivated crops. WD was used here as additive for the cultivation of tomato (Solanum lycopersicum L.) plants. The application improved quality (chemical) parameters, minerals, polyphenols, and lycopene contents of tomato fruits. The extracts of WD-treated and untreated tomatoes have been chemically and biologically characterized. The 1 H-NMR and ESI-mass spectrometry analyses of the extracts revealed the presence of different fatty acids, amino acids and sugars. In particular, the WD-treated tomatoes showed the presence of pyroglutamic acid and phloridzin derivatives, but also dihydrokaempferol, naringenin glucoside, cinnamic acid, and kaempferol-3-O-glucoside. When tested in cells, the extracts showed a promising anti-inflammatory profile in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Furthermore, the extracts displayed a slight vasorelaxant activity on rat aorta rings (either endothelium-denuded or endothelium-intact) pre-contracted with phenylephrine or potassium chloride. PRACTICAL APPLICATION: Wood distillate has been used for tomato plant growth. Tomatoes showed improved nutritional parameters, and their extracts displayed antioxidant and anti-inflammatory activities

First assessment of POPs and cytochrome P450 expression in Cuvier's beaked whales (Ziphius cavirostris) skin biopsies from the Mediterranean Sea

The Cuvier's beaked whale (Ziphius cavirostris) is one of the least known cetacean species worldwide. The decreasing population trend and associated threats has led to the IUCN categorising the Mediterranean subpopulation as Vulnerable on the Red List of Threatened Species. This study aimed to investigate for the first time the ecotoxicological status of Cuvier's beaked whale in the NW Mediterranean Sea. The study sampled around the 20% of the individuals belonging to the Ligurian subpopulation, collecting skin biopsies from free-ranging specimens. The levels of polychlorinated biphenyl (PCBs), polybrominated diphenyl ethers (PBDEs) and induction of cytochrome's P450 (CYP1A1 and CYP2B isoforms) were evaluated. Results highlighted that the pattern of concentration for the target contaminants was PCBs > PBDEs and the accumulation values were linked to age and sex, with adult males showing significantly higher levels than juvenile. Concerns raised by the fact that 80% of the individuals had PCB levels above the toxicity threshold for negative physiological effects in marine mammals. Therefore, these findings shed light on this silent and serious threat never assessed in the Mediterranean Cuvier's beaked whale population, indicating that anthropogenic pressures, including chemical pollution, may represent menaces for the conservation of this species in the Mediterranean Sea.This work was partially supported by the Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ), Grant Number: 13.6257.3-002.00–81197130, within the Plastic Busters Project-SDSN Solution Initiative. The authors are grateful to Francesco Rebagliati and all CETASMUS interns

Anthropogenic contaminants in Indo-Pacific humpback and Australian snubfin dolphins from the central and southern Great Barrier Reef

We present the first evidence of accumulation of organochlorine compounds (DDTs, PCBs, HCB) and polycyclic aromatic hydrocarbons (PAHs) in Indo-Pacific humpback and Australian snubfin dolphins from the central and southern Great Barrier Reef. These dolphins are considered by the Great Barrier Marine Park Authority to be high priority species for management. Analyses of biopsy samples, collected from free ranging individuals, showed PAHs levels comparable to those reported from highly industrialized countries. DDTs and HCB were found at low levels, while in some individuals, PCBs were above thresholds over which immunosuppression and reproductive anomalies occur. These results highlight the need for ongoing monitoring of these and other contaminants, and their potential adverse effects on dolphins and other marine fauna. This is particularly important given the current strategic assessment of the Great Barrier Reef World Heritage Area being undertaken by the Australian Government and the Queensland Government