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Efficacy of methylprednisolone on T-2 toxin-induced cardiotoxicity in vivo: A pathohistological study

Jaćević V, Wu Q, Nepovimova E, Kuča K

Environ Toxicol Pharmacol, 2019 Oct;71:103221.
PMID: 31365892 DOI: 10.1016/j.etap.2019.103221

Our aim was to compare the protective efficacy of two different formulations of methylprednisolone in T-2 toxin-induced cardiomyopathy. Methylprednisolone (soluble form, Lemod-solu® and/or depot form, Lemod-depo®, a total single dose of 40 mg/kg im) was given immediately after T-2 toxin (1 LD50 0.23 mg/kg sc). The myocardial tissue samples were examinated by using histopathology, semiquantitative and imaging analyses on day 1, 7, 14, 21, 28 and 60 of the study. Therapeutic application of Lemod-solu® significantly decreased the intensity of myocardial degeneration and haemorrhages, distribution of glycogen granules in the endo- and perimysium, a total number of mast cells and the degree of their degranulation was in correlation with the reversible heart structural lesions (p 
Cardiomyopathy induced by T-2 toxin in rats

Jaćević V, Wu Q, Nepovimova E, Kuča K

Food Chem Toxicol, 2020 Jan 22.
PMID: 31981685 DOI: 10.1016/j.fct.2020.111138

T-2 toxin, A trichothecenes mycotoxin, is immunotoxic to animals and humans. Although it is highly cardiotoxic, the pathogenesis of cardiomyopathy caused by T-2 toxin is not entirely clear. Hence, in our research, cardiomyopathy was induced by a single injection of T-2 mycotoxin (0.23 mg/kg s.c., 1 LD50.) to Wistar rats. The cardiac tissue was carefully examinated by using basic histopathology, semiquantitative (tissue grading score scales) and imaging (a total number of mast cells - MCs) analyses on days 1, 7, 14, 21, 28 and 60 of the study. The most intensive myocardial alterations (cardiac damage score, CDS = 4.20-4.40), irregular glycogen distribution (glycogen distribution score, GDS = 4.07-4.17), haemorrhagic foci (vascular damage score, VDS = 4.57-4.90), diffuse accumulation and degranulation of MCs were observed on day 28 and 60 after treatment (p 
Jatropha gossypiifolia L. and its biologically active metabolites: A mini review

Wu Q, Patocka J, Nepovimova E, Kuca K

J Ethnopharmacol, 2019 Apr 24;234:197-203.
PMID: 30695706 DOI: 10.1016/j.jep.2019.01.022

ETHNOPHARMACOLOGICAL RELEVANCE: Jatropha gossypiifolia L. (Euphorbiaceae) is popularly known as bellyache bush or black physic nut and is widely used in local / traditional medicine due to the various biological activities attributed to its different parts, including its leaves, roots, and latex.
AIM OF THE STUDY: In this review, we aim to update and discuss the chemistry, specific pharmacology, and toxicological activities of Jatropha gossypiifolia and its bioactive metabolites.
MATERIALS AND METHODS: The Web of Science, PubMed, Google Scholar, SciFinder, Cochrane Library, Scopus, and Science Direct databases were searched with the name "Jatropha gossypiifolia" and the term "bioactive metabolites". All studies on the chemistry, pharmacology, and toxicology of the plant up to December 2018 were included in this review.
RESULTS: Jatropha gossypiifolia leaves are considered to have anti-inflammatory, antimicrobial and insecticidal properties. The root and stem have anti-inflammatory and antimicrobial properties. The seeds and fruits can be used against influenza and as a sedative, analgesic or anti-diarrheal agents. The latex is bactericidal and molluscicidal. Topical application of latex is used to treat wounds and bites of venomous animals. The diluted form is usually used for the treatment of diarrhoea by indigenous peoples.
CONCLUSIONS: The main pharmacological activities of Jatropha gossypiifolia include anti-inflammatory, antineoplastic, antimicrobial, antioxidant, and anticholinesterase, and antihypertensive activities. Species of Jatropha are notably known for their toxic potential, and their toxicity is primarily related to the latex and seed contents. However, the potential mechanisms of these pharmacological activities have not been fully explored. We hope this review will help to further inform the potential utilization of Jatropha gossypiifolia in complementary and alternative medicine.
Interspecies and intergender differences in acute toxicity of K-oximes drug candidates

Jaćević V, Nepovimova E, Kuča K

Chem Biol Interact, 2019 Aug 01;308:312-316.
PMID: 31153983 DOI: 10.1016/j.cbi.2019.05.035

K-oximes were developed as modern drug candidates acting as AChE reactivators. In this study, it has been investigated which interspecies and intergender differences changes could be observed in Wistar rats and Swiss mice, both genders, after the treatment with increasing doses of selected acetylcholinesterase reactivators - asoxime, obidoxime, K027, K048, and K075. After the 24 h, a number of died animals was counted and the median lethal dose (LD50) for each oxime was calculated. By using the intramuscular route of administration, asoxime and K027 had the least toxicity in female rats (640.21 mg/kg and 686.08 mg/kg), and in female mice (565.75 mg/kg and 565.74 mg/kg), respectively. Moreover, asoxime and K027 showed 3, 4 or 8 times less acute toxicity in comparison to K048, obidoxime and K075, respectively. Beyond, K075 had the greatest toxicity in male rats (81.53 mg/kg), and in male mice (57.34 mg/kg), respectively. Our results can help to predict likely adverse toxic effects, target organ systems and possible outcome in the event of massive human overexposure, and in establishing risk categories or in dose selection for the initial repeated dose toxicity tests to be conducted for each oxime.
Fulltext Simvastatin Inhibits Endotoxin-Induced Apoptosis in Liver and Spleen Through Up-Regulation of Survivin/NF-κB/p65 Expression

Nežić L, Amidžić L, Škrbić R, Gajanin R, Nepovimova E, Vališ M, et al.

Front Pharmacol, 2019;10:54.
PMID: 30828299 DOI: 10.3389/fphar.2019.00054

Endotoxemia is associated by dysregulated apoptosis of immune and non-immune cells. We investigated whether simvastatin has anti-apoptotic effects, and induces hepatocytes and lymphocytes survival signaling in endotoxin-induced liver and spleen injuries. Wistar rats were divided into the groups pretreated with simvastatin (20 or 40 mg/kg, orally) prior to a non-lethal dose of lipopolysaccharide (LPS), the LPS group, and the control. The severity of tissue inflammatory injuries was expressed as hepatic damage scores (HDS) and spleen damage scores (SDS), respectively. The apoptotic cell was detected by TUNEL (Terminal deoxynucleotidyl transferase dUTP Nick End Labeling) and immunohistochemical staining (expression of cleaved caspase-3, and anti-apoptotic Bcl-xL, survivin and NF-κB/p65). Simvastatin dose-dependently abolished HDS and SDS induced by LPS (p < 0.01), respectively. Simvastatin 40 mg/kg significantly decreased apoptotic index and caspase-3 cleavage in hepatocytes and lymphocytes (p < 0.01 vs. LPS group, respectively), while Bcl-XL markedly increased accordingly with simvastatin doses. In the simvastatin, groups were determined markedly increased cytoplasmic expression of survivin associated with nuclear positivity of NF-κB, in both hepatocytes and lymphocytes (p < 0.01 vs. LPS group). Cell-protective effects of simvastatin against LPS seemed to be mediated by up-regulation of survivin, which leads to reduced caspase-3 activation and inhibition of hepatocytes and lymphocytes apoptosis.
Fulltext Phytoantioxidant Functionalized Nanoparticles: A Green Approach to Combat Nanoparticle-Induced Oxidative Stress

Balkrishna A, Kumar A, Arya V, Rohela A, Verma R, Nepovimova E, et al.

Oxid Med Cell Longev, 2021;2021:3155962.
PMID: 34737844 DOI: 10.1155/2021/3155962

Nanotechnology is gaining significant attention, with numerous biomedical applications. Silver in wound dressings, copper oxide and silver in antibacterial preparations, and zinc oxide nanoparticles as a food and cosmetic ingredient are common examples. However, adverse effects of nanoparticles in humans and the environment from extended exposure at varied concentrations have yet to be established. One of the drawbacks of employing nanoparticles is their tendency to cause oxidative stress, a significant public health concern with life-threatening consequences. Cardiovascular, renal, and respiratory problems and diabetes are among the oxidative stress-related disorders. In this context, phytoantioxidant functionalized nanoparticles could be a novel and effective alternative. In addition to performing their intended function, they can protect against oxidative damage. This review was designed by searching through various websites, books, and articles found in PubMed, Science Direct, and Google Scholar. To begin with, oxidative stress, its related diseases, and the mechanistic basis of oxidative damage caused by nanoparticles are discussed. One of the main mechanisms of action of nanoparticles was unearthed to be oxidative stress, which limits their use in humans. Secondly, the role of phytoantioxidant functionalized nanoparticles in oxidative damage prevention is critically discussed. The parameters for the characterization of nanoparticles were also discussed. The majority of silver, gold, iron, zinc oxide, and copper nanoparticles produced utilizing various plant extracts were active free radical scavengers. This potential is linked to several surface fabricated phytoconstituents, such as flavonoids and phenols. These phytoantioxidant functionalized nanoparticles could be a better alternative to nanoparticles prepared by other existing approaches.