Oxidative stress is the subject of numerous studies, most of them focusing on the negative effects exerted at both molecular and cellular levels, ignoring the possible benefits of free radicals. More and more people admit to having heard of the term “oxidative stress”, but few of them understand the meaning of it. We summarized and analyzed the published literature data in order to emphasize the importance and adaptation mechanisms of basal oxidative stress. This review aims to provide an overview of the mechanisms underlying the positive effects of oxidative stress, highlighting these effects, as well as the risks for the population consuming higher doses than the recommended daily intake of antioxidants. The biological dose–response curve in oxidative stress is unpredictable as reactive species are clearly responsible for cellular degradation, whereas antioxidant therapies can alleviate senescence by maintaining redox balance; nevertheless, excessive doses of the latter can modify the redox balance of the cell, leading to a negative outcome. It can be stated that the presence of oxidative status or oxidative stress is a physiological condition with well-defined roles, yet these have been insufficiently researched and explored. The involvement of reactive oxygen species in the pathophysiology of some associated diseases is well-known and the involvement of antioxidant therapies in the processes of senescence, apoptosis, autophagy, and the maintenance of cellular homeostasis cannot be denied. All data in this review support the idea that oxidative stress is an undesirable phenomenon in high and long-term concentrations, but regular exposure is consistent with the hormetic theory.

Off-label use of drugs is widely known as unapproved use of approved drugs, and it can be perceived as a relatively simple concept. Even though it has been in existence for many years, prescribing and dispensing of drugs in an off-label regimen is still a current issue, triggered especially by unmet clinical needs. Several therapeutic areas require off-label approaches; therefore, this practice is challenging for prescribing physicians. Meanwhile, the regulatory agencies are making efforts in order to ensure a safe practice. The present paper defines the off-label concept, and it describes its regulation, together with several complex aspects associated with clinical practices regarding rare diseases, oncology, pediatrics, psychiatry therapeutic areas, and the safety issues that arise. A systematic research of the literature was performed, using terms, such as “off-label”, ”prevalence”, ”rare diseases”, ”oncology”, ”psychiatry”, ”pediatrics”, and ”drug repurposing”. There are several reasons for which off-label practice remains indispensable in the present; therefore, efforts are made worldwide, by the regulatory agencies and governmental bodies, to raise awareness and to ensure safe practice, while also encouraging further research.

The literature provides scientific evidence for the beneficial effects of cannabidiol (CBD), and these effects extend beyond epilepsy treatment (e.g., Lennox–Gastaut and Dravet syndromes), notably the influence on oxidative status, neurodegeneration, cellular protection, cognitive function, and physical performance. However, products containing CBD are not allowed to be marketed everywhere in the world, which may ultimately have a negative effect on health as a result of the uncontrolled CBD market. After the isolation of CBD follows the discovery of CB1 and CB2 receptors and the main enzymatic components (diacylglycerol lipase (DAG lipase), monoacyl glycerol lipase (MAGL), fatty acid amino hydrolase (FAAH)). At the same time, the antioxidant potential of CBD is due not only to the molecular structure but also to the fact that this compound increases the expression of the main endogenous antioxidant systems, superoxide dismutase (SOD), and glutathione peroxidase (GPx), through the nuclear complex erythroid 2-related factor (Nrf2)/Keep1. Regarding the role in the control of inflammation, this function is exercised by inhibiting (nuclear factor kappa B) NF-κB, and also the genes that encode the expression of molecules with a pro-inflammatory role (cytokines and metalloproteinases). The other effects of CBD on cognitive function and physical performance should not be excluded. In conclusion, the CBD market needs to be regulated more thoroughly, given the previously listed properties, with the mention that the safety profile is a very good one.

In the present study, a HPLC/DAD method was set up to allow for the determination and quantification of malondialdehyde (MDA) in the brain of rodents (rats). Chromatographic separation was achieved on Supelcosil LC-18 (3 μm) SUPELCO Column 3.3 cm × 4.6 mm and Supelco Column Saver 0.5 μm filter by using a mobile phase acetonitrile (A) and phosphate buffer (20 mM, pH = 6) (B). Isocratic elution was 14% for (A) and 86% for (B). The injection volume (loop mode) was 100 μL with an analysis time of 1.5 min. Flow rate was set at 1 mL/min. The eluted compound was detected at 532 nm by a DAD detector by keeping the column oven at room temperature. The results indicated that the method has good linearity in the range of 0.2–20 μg/g. Both intra- and inter-day precision, expressed as RSD, were ≤15% and the accuracies ranged between ±15%. The lower limit of quantification (LLOQ), stability, and robustness were evaluated and satisfied the validation criteria. The method was successfully applied in a study of chronic toxicology following different treatment regimens with haloperidol and metformin.

Selective androgen receptor modulators (SARMs) are substances of increasingly interest in the medical area due to the anabolic effect on muscle and bone tissue. Even if they aren`t yet introduced into therapy, they are in various stages of experimental and clinical research for pathologies involving catabolic states in protein metabolism. These molecules manage to dissociate the anabolic effect from the virilising effect, compared with androgenic hormones, due to the non-steroidal structure that they detain. Having this pharmacological advantage, besides the possibility of being orally administered, these substances are used illegally by athletes and bodybuilders. It is important to note that SARMs are prohibited for performance athletes by World Anti-Doping Agency (WADA), but the concern is that they can be easily obtained from various uncertain sources. Moreover, their pharmacotoxicological profile is not clearly known, so their chronic administration, in high doses, represents a possible risk for the health. RezumatModulatorii selectivi ai receptorilor androgenici (SARM) sunt substanțe de interes crescut în aria medicală datorită efectelor anabolice la nivelul țesutului muscular și osos. Chiar dacă nu sunt introduse încă în terapie, sunt incluse în diverse stadii de cercetare experimentală și clinică pentru tratarea patologiilor cu stări catabolice în metabolismul proteic. Aceste molecule reușesc să disocieze efectul anabolic de cel virilizant, în comparație cu hormonii androgeni, datorită structurii lor nesteroidice. Deținând acest avantaj farmacologic, pe lângă posibilitatea de a fi administrate oral, aceste substanțe se utilizează în scop ilicit de către atleți și culturiști. Este important de menționat faptul că aceste substanțe sunt interzise sportivilor de performanță de către World-Anti Doping Agency (WADA), dar totuși pot fi ușor de procurat din diverse surse nesigure. În plus, profilul lor farmacotoxicologic nu este suficient cunoscut, deci administrarea cronică, în doze mari, reprezintă un posibil risc pentru sănătate.