Abstract
The purpose of this study was to evaluate the in vivo biological potential of new azetidine-2-one derivatives of ferulic acid (6a–f). First, the in vivo acute toxicity of azetidine-2-one derivatives of ferulic acid on Swiss white mice was investigated and, based on the obtained results, it can be stated that the studied derivatives belong to compounds with moderate toxicity. The in vivo anti-inflammatory potential of these derivatives was determined in a model of acute inflammation induced by carrageenan in rats and in a chronic inflammation model induced in rats using the granuloma test. In the acute inflammation model, all the studied compounds had a maximum anti-inflammatory effect 24 h after administration, which suggests that these compounds may be classified, from a pharmacokinetic point of view, in the category of long-acting compounds. The most active compound in the series was found to be compound 6b. In the case of the chronic inflammation model, it was observed that the studied compounds (6a–f) reduced the formation of granulation tissue compared to the control group, having an intense effect of inhibiting the proliferative component. The most important inhibitory effect of inhibiting the proliferative component was recorded for compound 6b. Additionally, the investigation of liver function was performed by determining the serum levels of liver enzymes aspartate transaminase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and bilirubin (total and direct). The results showed that, in the series of azetidin-2-one derivatives, the liver enzymes concentration values were close to those recorded for the reference anti-inflammatories (diclofenac sodium and indomethacin) and slightly higher compared to the values for the healthy control group. At the end of the experiment, the animals were euthanized and fragments of liver, lung, and kidney tissue were taken from all groups in the study. These were processed for histopathological examination, and we noticed no major changes in the groups treated with the azetidine 2-one derivatives of ferulic acid compared to the healthy groups.
Highlights
Free radical damage leads to oxidative stress-related disorders, including inflammatory diseases [1].An inflammatory process in cellular and tissue levels is an important stress factor for the human organism which can trigger chronic diseases, including diabetes, cancer, cardiovascular diseases, arthritis, obesity, and autoimmune diseases.Inflammation is a complex defense mechanism to harmful stimuli from different biological and environmental sources in order to restore an injured tissue by the inflammation cascade [2].Depending on the involved immune factors and the duration of the process, inflammation has been classified as an acute and chronic process
Acute inflammation is caused by cellular and vascular reactions which are responsible for the clinical symptoms of inflammation, and chronic inflammation occurs when the human organism is exposed to foreign bodies, chemical agents, and specific pathogens [2]
The acute toxicity was assessed by the lethal dose 50 assay, the tested compounds being administered in various concentrations (500–6500 mg/kg body weight) orally as emulsions in Tween 80 and the survival rate was monitored over a period of 24 h, 48 h, 72 h, 7 d, and 14 d after administration
Summary
Free radical damage leads to oxidative stress-related disorders, including inflammatory diseases [1].An inflammatory process in cellular and tissue levels is an important stress factor for the human organism which can trigger chronic diseases, including diabetes, cancer, cardiovascular diseases, arthritis, obesity, and autoimmune diseases.Inflammation is a complex defense mechanism to harmful stimuli from different biological and environmental sources in order to restore an injured tissue by the inflammation cascade [2].Depending on the involved immune factors and the duration of the process, inflammation has been classified as an acute and chronic process. Free radical damage leads to oxidative stress-related disorders, including inflammatory diseases [1]. An inflammatory process in cellular and tissue levels is an important stress factor for the human organism which can trigger chronic diseases, including diabetes, cancer, cardiovascular diseases, arthritis, obesity, and autoimmune diseases. Depending on the involved immune factors and the duration of the process, inflammation has been classified as an acute and chronic process. Acute inflammation is caused by cellular and vascular reactions which are responsible for the clinical symptoms of inflammation, and chronic inflammation occurs when the human organism is exposed to foreign bodies, chemical agents, and specific pathogens [2]. Antioxidant and anti-inflammatory agents may be useful as valuable drugs for inflammatory diseases [1]
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