Journal of Experimental Pharmacology and Toxicology doi: 10.6425/022025jept004

Authors: Amalia Ridichie Adriana Ledeti Răzvan Bertici Ionuț Ledeți

Estrogens represent a class of cholesterol-derived female sex hormones, essential in the regulation of numerous physiological processes. On the basis of their origin, they can be classified into endogenous (synthesized within the body) or exogenous (introduced from external sources) compounds. In humans, four types of endogenous estrogens have been identified, namely estrone, 17-β-estradiol, estriol, and estetrol. Despite their similarities in chemical structures, they have distinct receptor affinities and functional roles at different life stages. This review presents, in addition to an overview of their diverse physiological functions, a discussion of the three estrogen receptors (ERα, ERβ, and GPER1) currently investigated as possible targets in the development of new therapeutic strategies for hormone-dependent breast cancer.

Journal of Experimental Pharmacology and Toxicology doi: 10.6425/022025jept005

Authors: Ștefania Dinu Adrian Moldoveanu Camelia Szuhanek Raluca Milutinovici Diana Haj Ali Șerban Talpoș

1. Background/Objectives: Calcium phosphate biomaterials (CPBs), including hydroxyapatite (HA), are among the most commonly used biomaterials in dentistry due to their biocompatibility and similarity to the body’s hard tissues. This review aims to highlight the clinical applications of CPBs in dentistry, focusing mainly on hydroxyapatite and its modern formulations. 2. Methods: A literature search was conducted by analyzing data published up to May 2025 in databases such as PubMed, Web of Science, and Google Scholar using keyword combinations such as “Biomaterials”, “dentistry”, “calcium phosphate”, and “hydroxyapatite”. 3. Results: The findings of this work reveal the wide clinical use of HA, including tooth remineralization, implant coating, bone grafting, and the treatment of dental hypersensitivity. Furthermore, the novel formulations of hydroxyapatite have substantially improved its therapeutic and physicochemical characteristics. 4. Conclusions: The clinical relevance of HA and its modern formulations emphasizes the need for continuous research that will contribute to further enhancement of HA’s therapeutic outcomes.

Journal of Experimental Pharmacology and Toxicology doi: 10.6425/022025jept006

Authors: Anca-Maria Căpraru Simona Ardelean Nicoleta Zurbău-Anghel Adriana Maria Dărăban Melania Munteanu Andreea Ioana Rusu

Cervical cancer remains a significant global health issue, closely linked to persistent human papillomavirus (HPV) infections. Vitamin D, recognized primarily for its role in calcium homeostasis and bone metabolism, has emerged as a promising preventive and therapeutic agent in cancer management. Recent clinical studies have suggested that vitamin D may effectively prevent cervical cancer and aid in the regression of early cervical dysplasia (CIN 1 orc LSIL). However, its therapeutic impact appears limited for advanced cervical dysplasia (CIN 2/3, HSIL) and established cervical cancer cases. Due to the progressive nature of cervical lesions, vitamin D supplementation represents a potentially valuable strategy for secondary prevention. This review critically evaluates current clinical evidence, underscores key insights into vitamin D’s role in cervical cancer management, and highlights existing gaps requiring further research.

Journal of Experimental Pharmacology and Toxicology doi: 10.6425/022025jept002

Authors: Slavița Rotunjanu Raluca Pop Marius Mioc Mihaela Jorgovan Elisabeta Atyim Codruța Șoica

Porphyrins are a class of naturally occurring intensely colored compounds (ranging in color from red to violet) with a macrocyclic structure. Both as free base and containing a central metal (metalloporphyrins), they have found various applications in pharmaceutical and medical fields. One of the most important properties of these compounds is represented by their tunable properties, given the various metals and substituents that can be employed. The present study dealt with the investigation, by means of computational chemistry, of the energetic and geometric properties of a series of proposed Dy(III)-porphyrins. The influence of various substituents grafted off the porphyrin macrocycle is discussed as a function of the calculated properties, like the frontier molecular orbitals energies, molecular area and volume, polarizability, and polar surface area.

Journal of Experimental Pharmacology and Toxicology doi: 10.6425/022025jept001

Authors: Iasmina-Alexandra Predescu Alexandra-Denisa Semenescu Dalia Pătrașcu

Background: Melanoma is the most aggressive skin cancer, and the development of new therapeutic strategies is essential. The synthesis of silver nanoparticles (AgNPs) using Punica granatum (PG) peel extract offers a sustainable approach with potential biomedical applications. Methods: The human melanoma cell line RPMI-7951 was used in this study to assess the effects of AgNPs which were produced with ethanolic PG peel extract. The MTT assay was used to measure cytotoxicity, and morphological analysis, Hoechst, and mitochondrial staining were used to assess the cellular response. Results: PG-AgNPs induced a dose-dependent reduction in cell viability, with significant effects observed at concentrations of 25 and 30 μg/mL. Treated cells showed decreased confluency, shrinkage, chromatin condensation, and mitochondrial changes. Conclusions: These findings demonstrate that PG-AgNPs exert cytotoxic effects on melanoma cells and highlight their potential as promising candidates for anticancer therapies, supporting further validation in in vivo models.

Journal of Experimental Pharmacology and Toxicology doi: 10.6425/022025jept003

Authors: Andreea Milan Marius Mioc Alexandra Prodea Codruța Șoica

Despite its notable anticancer potential, betulinic acid (BA) exhibits limited bioavailability that hampers its therapeutic efficacy. To address this issue, betulinic acid fatty esters were previously synthesized by employing stearic (St-BA), palmitic (Pal-BA), and butyric acids (But-BA), and further incorporated into surface-modified liposomal formulations (St-BA-Lip, Pal-BA-Lip, But-BA-Lip). The BA derivatives, as well as their liposomal formulations, were assessed against three human cancer cell lines: colorectal adenocarcinoma Caco-2 cells, ovarian teratocarcinoma PA-1, and alveolar epithelial adenocarcinoma A549 cells. All compounds exhibited cytotoxic effects in a time- and dose-dependent manner, more potently than the positive control, 5-fluorouracil (5-FU). But-BA-Lip exhibited the best anticancer effects against all tested cancer cell lines, recording lower IC50 values than the parent compound (BA) and 5-FU (15.55 μM against Caco-2 cells, 48.16 μM against PA-1 cells, and 25.3 μM against A549 cells). In silico molecular docking studies revealed that Pal-BA showed superior binding affinity to AKT/PKB than the parent compound, BA, while But-BA showed enhanced interaction with EGFR1. Both derivatives achieved 93% of the native ligand’s docking score, highlighting their therapeutic potential through structural modifications.

Journal of Experimental Pharmacology and Toxicology doi: 10.6425/012025jept002

Authors: Ramona Pârvănescu Ionica-Oana Alexa Cristina Dehelean Daiana Colibășanu Roxana Racoviceanu Radu Lazău Sanela Barbu Cristina Trandafirescu

The increase in the incidence of fungal infections and fungal resistance has prompted the research for better therapeutic strategies such as the optimization and improvement of existing antifungal drugs. Fluconazole, one of the most used and well-tolerated antifungal drugs has a series of drawbacks hampering the obtention of an optimal therapeutic response. Complexation with cyclodextrins represents a very-well known approach for improvement of pharmaceutical profile of drugs. The present study aims to obtain and to evaluate the solid inclusion complexes of fluconazole with methylated beta-cyclodextrin, as preliminary experiments in formulation of improved pharmaceutical product of fluconazole. The differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray powder diffractometry were used to characterize the binary systems between fluconazole and methylated-beta-cyclodextrin. The encapsulation of fluconazole into methylated-betacyclodextrin cavity resulted in modifications of the physicochemical properties of the antifungal agent. The formation of the fluconazole-cyclodextrin inclusion complex was confirmed by thermal and spectral methods. Based on the experimental data, a real interaction in solid state between the antifungal agent and cyclodextrin was proved, leading us to propose the kneading product in 1:1 molar ratio for future development of improved pharmaceutical formulation containing fluconazole.

Journal of Experimental Pharmacology and Toxicology doi: 10.6425/012025jept005

Authors: Diana Haj Ali Cristina Dehelean Corina Danciu

The Renin-Angiotensin-Aldosterone System (RAAS) is essential for blood pressure regulation and the body's homeostasis, with Angiotensin II (Ang II) playing a key role in vasoconstriction, sodium reabsorption, and cellular growth. Recent studies suggest that RAAS, particularly through the classical axis (renin → Ang I → ACE → Ang II → AT1 receptor), may contribute to cancer development by promoting cell migration, angiogenesis, and metastasis. Ang II, through AT1 receptors, activates pathways such as PI3K/AKT/mTOR and Ras/Raf/MEK/ERK, which enhance tumor progression. In contrast, the alternative RAAS axis (ACE2 → Ang-(1-7) → Mas receptor and AT2 receptors) shows potential anti-cancer effects. Angiotensin II receptor blockers (ARBs), such as candesartan, losartan, valsartan, and telmisartan, which inhibit the AT1 receptor, may reduce the pro-tumorigenic effects of RAAS. This suggests that the ARBs could be explored as a potential adjunctive in cancer therapy. However, further research is needed to fully understand their role in oncology considering that there are studies which paradoxically suggest that these compounds could induce carcinogenesis.

Journal of Experimental Pharmacology and Toxicology doi: 10.6425/012025jept001

Authors: Anca-Maria Căpraru Marius Belean Adriana Dărăban Adrian Crișan Mihai Roșu Carmen Neamțu Simona Ardelean

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality worldwide. Epidemiological studies have consistently inferred a correlation between high red meat consumption and an increased risk of CRC. This review examines the association between red meat intake and CRC development, emphasizing the role of dietary patterns, cooking methods, and processing techniques. Moreover, carcinogenic compounds such as heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), and Nnitroso compounds (NOCs) are formed during high-temperature cooking and processing of red meat, potentially contributing to colorectal carcinogenesis. Furthermore, genetic susceptibility and metabolic variations influence individual risk factors. Based on recent findings, dietary recommendations suggest limiting red and processed meat consumption while increasing fiber-rich foods to mitigate CRC risk. This article provides an overview of current evidence, underlying biochemical mechanisms that may impact CRC incidence through dietary modifications.

Journal of Experimental Pharmacology and Toxicology doi: 10.6425/012025jept003

Authors: Diana Sarbu Andreea Mihaela Kiș Adela Ramona Boroghina Mihaela Cristina Negru Mohamad Joma Asad Salehi Matin Ramona Amina Popovici

Periodontal disease is a common condition that affects a large part of the population. Periodontitis occurs when bacteria spread deeper into the tissue and the surroundings structures leading to a chronic, destructive, irreversible inflammatory disease. Oral Gram-positive and Gram-negative bacteria have been frequently identified in blood flow and may play a role in vascular disease. The objective of the study is to examine the relationship between microbial presence in dental plaque and periodontitis, focusing on how these microorganisms may enter the bloodstream, particularly in individuals with cardiovascular diseases. Patients with severe periodontal disease showed endothelial dysfunction and signs of systemic inflammation, placing them at an increased risk level for the development of cardiovascular diseases. Dental diseases including gingivitis, periodontitis, and other odontogenic infections have a higher bacteremia regarding valvular diseases after tooth extraction. Oral bacteria can cause short-term bacteremia during dental treatment especially when is involved periodontitis. Usually, the bacteria enter the circulation and reach body organs through blood, becoming a risk factor for cardiovascular diseases.

Journal of Experimental Pharmacology and Toxicology doi: 10.6425/012025jept004

Authors: Lina Haj Ali Larissa Dăniluc Loredana Suhov Radu Pecingina Mihaela Viviana Ivan

The coronavirus pandemic has significantly impacted a substantial part of the global population, and the cardiovascular repercussions of COVID-19 infection have been unveiled for the first time. While the arrhythmogenic effects of the severe inflammatory syndrome associated with the infection are well-established, another critical cause of arrhythmias, particularly ventricular arrhythmias such as ventricular tachycardia, torsades de pointes, or ventricular fibrillation, which can result in cardiac arrest, is the pharmacological treatment employed to manage the disease in hospitalized patients. Among all arrhythmogenic mechanisms, the QT interval prolongation is the most alarming. This review aims to provide a more in-depth exploration of these effects and the potential mechanisms underlying their occurrence.