Journal of Experimental Pharmacology and Toxicology

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article