Dilyana Doncheva-Stoimenova

Recently, nanosized graphene oxide (nGO) has gained significant scientific interest in biomedical strategies. However, before clinical translation, GO-based nanomaterials must be thoroughly evaluated for safety and biocompatibility. Therefore, this study investigated the in vivo effects of pristine GO and polyethylene glycol-functionalized GO (nGO-PEG) nanoparticles in male Long Evans rats, following repeated intraperitoneal administration (4 mg/kg body weight). The effects of the nanoparticles were assessed using a range of physiological and pathological markers including body weight (BW) gain, organ coefficients, diuresis, histological, hematological and biochemical parameters. Both nGO and nGO-PEG significantly suppressed BW gain and reduced diuresis in treated rats. Nanoparticle exposure resulted in significant kidney enlargement and reduced testes weight. Mild histological alterations were observed in all examined organs, with nGO showing a tendency toward slightly more pronounced changes than nGO-PEG. Serum levels of aspartate aminotransferase, alanine aminotransferase, and creatinine were significantly elevated in nGO-treated rats, whereas nGO-PEG significantly increased the urinary levels of creatinine and urea. Both nGO- and nGO-PEG-treated rats exhibited elevated serum glucose concentrations. Significant hematological changes were detected in rats treated with both nanoparticles with pronounced effects observed following nGO-PEG administration. Our results suggest possible hematological and metabolic disturbances, as well as hepatic injury and renal toxicity in rats at repeated exposure to nGO and nGO-PEG.

Increasing environmental contamination with microplastics (MPs) raises significant concerns regarding their potential impact on reproductive health. This study evaluated the effects of prolonged oral exposure to fluorescent polystyrene microplastics (FPS-MPs) of different sizes on the male reproductive system in Wistar rats. Juvenile male rats at 21 days of age were exposed to FPS-MPs of 1 µm and 5 µm for 52 days, covering the period of sexual maturation and a complete spermatogenesis cycle. Body weight, reproductive organ indices, serum levels of testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), as well as sperm motility and morphology, were assessed. Reproductive potential and accumulation of microplastics in reproductive tissues were also evaluated. No significant differences were observed in body weight or most reproductive organ indices, except for a slight reduction in the left epididymis index in the group exposed to 5 µm particles. FPS-MPs induced size-dependent changes in the hormonal profile, including decreases in T and E2 and compensatory increases in FSH and LH, as well as impairments in sperm quality, which were more pronounced in rats exposed to smaller particles. In conclusion, fertility potential remained preserved, while FPS-MPs accumulated in the testes and epididymides, demonstrating subclinical, size-dependent effects on the male reproductive system.

Background: Recently various plants have attracted considerable scientific interest as potential therapeutic alternatives to known drugs used in anti-inflammatory therapy. Therefore, we have investigated the possible anti-inflammatory and analgesic effects of aqueous extracts from flowers of the medical plant Nepeta nuda ssp. nuda L. (naked catmint) in a model of acute peripheral inflammation induced by intraplantar injection of λ-carrageenan in the hind paw of Long Evans rats. Methods: Two routes of N. nuda extract application were used: locally by intraplantar injections at dosages of 2.5 mg/kg and 25 mg/kg and systemically by intraperitoneal administration at dosages of 50 mg/kg and 200 mg/kg, respectively. Paw volume was measured prior to the carrageenan application and 1, 2, 3, and 4 h after carrageenan injection. Spontaneous locomotor activity of the rats was assessed 3 h after carrageenan injection, corresponding to the peak of acute paw inflammation. Results: Local application of the higher N. nuda dose led to a marked reduction in inflammatory paw edema at the 4th hour after carrageenan injection, comparable to the effect of the positive control diclofenac sodium. Interestingly, a similar anti-inflammatory effect was observed at the 1st hour when both extract doses were administered intraperitoneally. Only the higher intraplantar dose of N. nuda extract significantly enhanced the vertical activity in comparison to the group treated with carrageenan alone. Conclusions: Our data indicate that the aqueous N. nuda extract possesses potent anti-inflammatory effects following both local and systemic administration in rats. Furthermore, when administered locally the extract exerts significant analgesic activity in inflammatory pain.

The neurotoxin β-N-methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid produced by cyanobacteria. Non-neuronal toxicity of BMAA is poorly studied with a reported increase in reactive oxygen species and a decrease in the antioxidant capacity of liver, kidney, and colorectal adenocarcinoma cells. The aim of this research is to study the toxicity of BMAA (0.1–1 mM) on mitochondria and submitochondrial particles with ATPase activity, on the semicarbazide-sensitive amino oxidases (SSAOs) activity of rat liver, and on an in vitro model containing functionally active excitable tissues—regularly contracting heart muscle preparation with a preserved autonomic innervation. For the first time the BMAA-dependent inhibition of SSAO activity, the elimination of the positive inotropic effect of adrenergic innervation, and the direct and reversible inhibition of adrenaline signaling in ventricular myocytes with 1 mM BMAA were observed. Additionally, it is confirmed that 1 mM BMAA can activate mitochondrial ATPase indirectly. It is concluded that a higher dose of BMAA may influence multiple physiological and pathological processes as it slows down the degradation of biogenic amines, downregulates the sympathetic neuromediation, and embarrasses the cell signaling of adrenergic receptors.

Cylindrospermopsin (CYN) is a widely spread cyanotoxin that can occur in fresh water and food. This research aims to investigate CYN toxicity by studying the effects of drinking 0.25 nM of CYN-contaminated water from a natural source, and of the direct application of moderate concentrations of CYN on different animal targets. The chosen structures and activities are rat mitochondria inner membrane permeability, mitochondrial ATP synthase (ATPase) and rat liver diamine oxidase (DAO) activities (EC 1.4.3.22.), the force of the contraction of an excised frog heart preparation with functional innervation, and the viability of a human intestinal epithelial cell line (HIEC-6). The oral exposure to CYN decreased the reverse (hydrolase) activity of rat liver ATPase whereas its short-term, in vitro application was without significant effect on this organelle, DAO activity, heart contractions, and their neuronal regulation. The application of CYN reduced HIEC-6 cells’ viability dose dependently. It was concluded that CYN is moderately toxic for the human intestinal epithelial cells, where the regeneration of the epithelial layer can be suppressed by CYN. This result suggests that CYN may provoke pathological changes in the human gastrointestinal tract.