Oxidative stress is characterized by an imbalance between prooxidant and antioxidant species, leading to macromolecular damage and disruption of redox signaling and cellular control. It is a hallmark of various diseases including metabolic syndrome, chronic fatigue syndrome, neurodegenerative, cardiovascular, inflammatory, and age-related diseases. Several mitochondrial defects have been considered to contribute to the development of oxidative stress and known as the major mediators of the aging process and subsequent age-associated diseases. Thus, mitochondrial-targeted antioxidants should prevent or slow down these processes and prolong longevity. This is the reason why antioxidant treatments are extensively studied and newer and newer compounds with such an effect appear. Astaxanthin, a xanthophyll carotenoid, is the most abundant carotenoid in marine organisms and is one of the most powerful natural compounds with remarkable antioxidant activity. Here, we summarize its antioxidant targets, effects, and benefits in diseases and with aging.

Due to Earth’s changing climate, the ongoing and foreseeable spreading of mycotoxigenic Aspergillus species has increased the possibility of mycotoxin contamination in the feed and food production chain. These harmful mycotoxins have aroused serious health and economic problems since their first appearance. The most potent Aspergillus-derived mycotoxins include aflatoxins, ochratoxins, gliotoxin, fumonisins, sterigmatocystin, and patulin. Some of them can be found in dairy products, mainly in milk and cheese, as well as in fresh and especially in dried fruits and vegetables, in nut products, typically in groundnuts, in oil seeds, in coffee beans, in different grain products, like rice, wheat, barley, rye, and frequently in maize and, furthermore, even in the liver of livestock fed by mycotoxin-contaminated forage. Though the mycotoxins present in the feed and food chain are well documented, the human physiological effects of mycotoxin exposure are not yet fully understood. It is known that mycotoxins have nephrotoxic, genotoxic, teratogenic, carcinogenic, and cytotoxic properties and, as a consequence, these toxins may cause liver carcinomas, renal dysfunctions, and also immunosuppressed states. The deleterious physiological effects of mycotoxins on humans are still a first-priority question. In food production and also in the case of acute and chronic poisoning, there are possibilities to set suitable food safety measures into operation to minimize the effects of mycotoxin contaminations. On the other hand, preventive actions are always better, due to the multivariate nature of mycotoxin exposures. In this review, the occurrence and toxicological features of major Aspergillus-derived mycotoxins are summarized and, furthermore, the possibilities of treatments in the medical practice to heal the deleterious consequences of acute and/or chronic exposures are presented.

The small, basic, and cysteine-rich antifungal protein PAF is abundantly secreted into the supernatant by the β-lactam producerPenicillium chrysogenum. PAF inhibits the growth of various important plant and zoopathogenic filamentous fungi. Previous studies revealed the active internalization of the antifungal protein and the induction of multifactorial detrimental effects, which finally resulted in morphological changes and growth inhibition in target fungi. In the present study, we offer detailed insights into the mechanism of action of PAF and give evidence for the induction of a programmed cell death-like phenotype. We proved the hyperpolarization of the plasma membrane in PAF-treatedAspergillus nidulanshyphae by using the aminonaphtylethenylpyridinium dye di-8-ANEPPS. The exposure of phosphatidylserine on the surface ofA. nidulansprotoplasts by Annexin V staining and the detection of DNA strand breaks by TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) gave evidence for a PAF-induced apoptotic-like mechanism inA. nidulans. The localization of reactive oxygen species (ROS) by dichlorodihydrofluorescein diacetate and the abnormal cellular ultrastructure analyzed by transmission electron microscopy suggested that ROS-elicited membrane damage and the disintegration of mitochondria played a major role in the cytotoxicity of PAF. Finally, the reduced PAF sensitivity ofA. nidulansstrain FGSC1053, which carries a dominant-interfering mutation infadA, supported our assumption that G-protein signaling was involved in PAF-mediated toxicity.

Triadin is a multiple proteins family, some isoforms being involved in muscle excitation-contraction coupling, and some having still unknown functions. To obtain clues on triadin functions, we engineered a triadin knock-out mouse line and characterized the physiological effect of triadin ablation on skeletal muscle function. These mice presented a reduced muscle strength, which seemed not to alter their survival and has been characterized in the present work. We first checked in these mice the expression level of the different proteins involved in calcium homeostasis and observed in fast muscles an increase in expression of dihydropyridine receptor, with a large reduction in calsequestrin expression. Electron microscopy analysis of KO muscles morphology demonstrated the presence of triads in abnormal orientation and a reduction in the sarcoplasmic reticulum terminal cisternae volume. Using calcium imaging on cultured myotubes, we observed a reduction in the total amount of calcium stored in the sarcoplasmic reticulum. Physiological studies have been performed to evaluate the influence of triadin deletion on skeletal muscle function. Muscle strength has been measured both on the whole animal model, using hang test or electrical stimulation combined with NMR analysis and strength measurement, or on isolated muscle using electrical stimulation. All the results obtained demonstrate an important reduction in muscle strength, indicating that triadin plays an essential role in skeletal muscle function and in skeletal muscle structure. These results indicate that triadin alteration leads to the development of a myopathy, which could be studied using this new animal model.

The effects of the muscle relaxant dantrolene on steps of excitation-contraction coupling were studied on fast twitch muscles of rodents. To identify the site of action of the drug, single fibers for voltage-clamp measurements, heavy SR vesicles for calcium efflux studies and solubilized SR calcium release channels/RYRs for lipid bilayer studies were isolated. Using the double Vaseline-gap or the silicone-clamp technique, dantrolene was found to suppress the depolarization-induced elevation in intracellular calcium concentration ([Ca²+]_i) by inhibiting the release of calcium from the SR. The suppression of [Ca²+]_i was dose-dependent, with no effect at or below 1 μM and a 53 ± 8% (mean ± SEM, n = 9, cut fibers) attenuation at 0 mV with 25 μM of extracellularly applied dantrolene. The drug was not found to be more effective if injected than if applied extracellularly. Calculating the SR calcium release revealed an equal suppression of the steady (53 ± 8%) and of the early peak component (46 ± 6%). The drug did not interfere with the activation of the voltage sensor in as much as the voltage dependence of both intramembrane charge movements and the L-type calcium currents (I_Ca) were left, essentially, unaltered. However, the inactivation of I_Ca was slowed fourfold, and the conductance was reduced from 200 ± 16 to 143 ± 8 SF⁻¹ (n = 10). Dantrolene was found to inhibit thymol-stimulated calcium efflux from heavy SR vesicles by 44 ± 10% (n = 3) at 12 μM. On the other hand, dantrolene failed to affect the isolated RYR incorporated into lipid bilayers. The channel displayed a constant open probability for as long as 30–50 min after the application of the drug. These data locate the binding site for dantrolene to be on the SR membrane, but be distinct from the purified RYR itself.