Milena Mishonova

Prof. Dr. Milena Mishonova


Research Focus & Metrics

Academic Career Length

6Years (2021-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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8 January 2021 in Toxins
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MCMariella Chichova
Mariella Chichova
Oskan Bahidinov TasinovOskan Bahidinov Tasinov
Oskan Bahidinov Tasinov
MSMilena Shkodrova
Milena Shkodrova
MMMilena Mishonova
Milena Mishonova
ISIliyana Sazdova
Iliyana Sazdova
HGHristo Gagov
Hristo Gagov
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.

13 January 2024 in Nanomaterials
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Milena Keremidarska-MarkovaMilena Keremidarska-Markova
Milena Keremidarska-Markova
ISIliyana Sazdova
Iliyana Sazdova
BIBilyana Ilieva
Bilyana Ilieva
MMMilena Mishonova
Milena Mishonova
MSMilena Shkodrova
Milena Shkodrova
MCMariella Chichova
Mariella Chichova
The growing interest in graphene oxide (GO) for different biomedical applications requires thoroughly examining its safety. Therefore, there is an urgent need for reliable data on how GO nanoparticles affect healthy cells and organs. In the current work, we adopted a comprehensive approach to assess the influence of GO and its polyethylene glycol-modified form (GO-PEG) under near-infrared (NIR) exposure on several biological aspects. We evaluated the contractility of isolated frog hearts, the activity of two rat liver enzymes–mitochondrial ATPase and diamine oxidase (DAO), and the production of reactive oxygen species (ROS) in C2C12 skeletal muscle cells following direct exposure to GO nanoparticles. The aim was to study the influence of GO nanoparticles at multiple levels—organ; cellular; and subcellular—to provide a broader understanding of their effects. Our data demonstrated that GO and GO-PEG negatively affect heart contractility in frogs, inducing stronger arrhythmic contractions. They increased ROS production in C2C12 myoblasts, whose effects diminished after NIR irradiation. Both nanoparticles in the rat liver significantly stimulated DAO activity, with amplification of this effect after NIR irradiation. GO did not uncouple intact rat liver mitochondria but caused a concentration-dependent decline in ATPase activity in freeze/thaw mitochondria. This multifaceted investigation provides crucial insights into GOs potential for diverse implications in biological systems.

9 April 2026 in Toxics
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HKHristiyana Georgieva Kanzova
Hristiyana Georgieva Kanzova
MAMadlena Naneva Andreeva
Madlena Naneva Andreeva
YGYana Goranova
Yana Goranova
RIRosen Ivanov
Rosen Ivanov
SMStefan Manchev
Stefan Manchev
ETElina Tsvetanova
Elina Tsvetanova
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.

9 February 2023 in Toxins
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MSMilena Shkodrova
Milena Shkodrova
MMMilena Mishonova
Milena Mishonova
MCMariella Chichova
Mariella Chichova
ISIliyana Sazdova
Iliyana Sazdova
BIBilyana Ilieva
Bilyana Ilieva
HGHristo Gagov
Hristo Gagov
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.

26 October 2025 in Proceedings of the Bulgarian Academy of Sciences
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MMMilena Mishonova
Milena Mishonova
LKLea Koceva
Lea Koceva
Bissera PilichevaBissera Pilicheva
Bissera Pilicheva
PZPlamen Zagorchev
Plamen Zagorchev
PEPetar Eftimov
Petar Eftimov
ISIliyana Sazdova
Iliyana Sazdova
Nose-to-brain drug delivery is a promising method for the direct introduction of chemicals and structures into the brain, bypassing the systemic circulation and the blood-brain barrier. Indocyanine green (ICG) is a near-infrared-emitting dye that is minimally toxic to humans. It is widely used in photodynamic applications, particularly in angiography and for many intraoperative staining procedures. In our study, ICG was administered intranasally to rats, and its penetration into the brain was observed. ICG distribution was measured using a near-infrared excitation laser at 1, 4, and 24 hours after administration as a solution into the rat nasal cavity near the olfactory mucosa. As a result, significant staining of the olfactory bulb and brainstem – mainly in the basolateral region of the pons – was observed in all cases, with the strongest signal detected at four hours. A more rapid decline in signal intensity was observed in the brainstem compared to the olfactory bulbs. These findings suggest that ICG readily crosses the nasal mucosal barrier and reaches the olfactory bulbs and brainstem via the olfactory and trigeminal nerve pathways, respectively. Additionally, ICG appears to be a useful dye for labelling molecules and supramolecular structures in studies of nose-to-brain delivery and whole-body distribution.

Verified
Journal Article
Open access
PDF file
MMMilena Mishonova
Milena Mishonova
LKLea Koceva
Lea Koceva
Bissera PilichevaBissera Pilicheva
Bissera Pilicheva
PZPlamen Zagorchev
Plamen Zagorchev
NRNeli Raikova
Neli Raikova
ISIliyana Sazdova
Iliyana Sazdova
This study aims to assess the rate and duration of rat brain retention after a single intranasal administration of indocyanine green (ICG) as an aqueous solution or encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles. Near-infrared fluorescence emission of ICG from the brain and visceral organs was measured at 1, 4, and 24 h, as well as at 1 and 2 weeks after administration. It was observed that both ICG formulations stained the olfactory bulbs and brainstem, the latter mainly in the basolateral region of the pons. Reduced staining was observed on day 7 after treatment, and the signal remains detectable on day 14. Additionally, while emission from ICG-labeled brains in water decreased after two weeks compared to day 7, in ICG-loaded nanoparticles, the emission was significantly higher on day 14. It is concluded that ICG is transported into the brain via both nose-to-brain delivery pathways—through and along olfactory or trigeminal nerves—and that ICG is a useful dye for in vivo studies due to its long-lasting emission and low toxicity. Furthermore, the suggested penetration of ICG-encapsulated PLGA nanoparticles via these transport mechanisms makes them a useful carrier for brain delivery of substances that are rapidly eliminated from circulation or do not cross the blood–brain barrier.