Type 2 diabetes mellitus (T2DM) increases the risk of cardiovascular disease, especially myocardial injury. Due to their hypoglycemic effects, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are efficiently used for T2DM management. GLP-1RAs also have anti-inflammatory and antioxidative effects, and can improve cardiac function. The aim of this study was to investigate the cardioprotective effects of liraglutide, a GLP-1RA, on isoprenaline-induced myocardial injury in rats. The study included 4 groups of animals. They were pretreated with saline for 10 days + saline on days 9 and 10 (control), saline for 10 days + isoprenaline on days 9 and 10 (isoprenaline group), liraglutide for 10 days + saline on days 9 and 10 (liraglutide group), and liraglutide for 10 days and on days 9 and 10 they were administered isoprenaline. This study evaluated ECG, myocardial injury markers, oxidative stress markers, and pathohistological changes. The results showed that liraglutide mitigated the isoprenaline-induced cardiac dysfunction recorded by ECG. Liraglutide reduced serum markers of myocardial injury such as high-sensitive troponin I, aspartate aminotransferase, alanine aminotransferase, reduced TBARS, increased catalase and superoxide dismutase activity and increased reduced glutathione, and improved lipid profile. Liraglutide induced antioxidative protection and alleviated isoprenaline-induced myocardial injury.

Background/Aim: Due to the numerous beneficial effects of pomegranate that can be explained through its antioxidative effects, the aim of this study was to determine the antioxidant potential of pomegranate peel extract (PoPEx) prepared from pomegranate that was harvested in the southeast region of Herze-govina (Bosnia and Herzegovina), through in vitro and in vivo studies. Methods: In PoPEx total phenols, flavonoids, flavonols, flavan-3-ols and antho-cyanins content was determined, as well as several antioxidative assays, including 2,2 diphenyl-1-picrylhydrazyl assay (DPPH), 2,2'-azino bis(3-ethylbenzothi-azoline-6-sulphonic acid) assay (ABTS), iron (III)-2,4,6-tripyridyl-S-triazine complex assay (FRAP), reduction of copper(II) ions (CUPRAC) assay, Briggs-Rauscher oscillatory reactions, neutralisation of OH radicals and lipid peroxidation assay. In vivo studies were performed by administrating 100 mg/ kg of body weight of PoPEx to the rats by gavage for 7 days, after which the rats were euthanised and prooxidative parameters (thiobabrituric acid reactive substances-TBARS as an index of lipid peroxidation, nitrites-NO 2 , hydrogen peroxide-H 2 O 2 and superoxide anion radical O 2-) were determined in plasma, as well as antioxidative parameters (superoxide dismutase-SOD, reduced gluta-thione-GSH and catalase-CAT) in erythrocyte lysates. Results: High content of phenolic compounds was found in PoPEx, which resulted in high antioxidative potential in all in vitro tests performed. In vivo study showed that PoPEx administration caused a significant decrease in TBARS, NO 2-, as well as an increase in reduced glutathione (p < 0.05) in comparison to the control group, while H 2 O 2 and O 2 * showed a lowering trend and SOD and CAT showed an increasing trend in PoPEx group, but without statistical significance. Conclusion: PoPEx demonstrated high antioxidative capacity measured in vitro and in vivo and can be potentially used as a supplement treatment in the prevention of various inflammatory conditions.

This paper presents the result of a combined employment of Analytical Quality-by-Design and Green Analytical Chemistry principles for the development of a robust high-performance liquid chromatography method for simultaneous determination of fixed-dose combination of three drugs, perindopril tert-butylamine, amlodipine besylate and indapamide. Optimum conditions were achieved on ZORBAX Eclipse XDB-C18 column (150 mm × 4.6 mm, 5 μm particle size), the mobile phase comprising acetonitrile and phosphate buffer (30 mM, pH 2.7) in the ratio 34:66 (v/v), the flow rate of 1 mL min−1, injection volume of 10 μL and UV detection at 210 nm. By assigning the design space from the overlay plot, the regions within which the robustness of the method is achieved were defined and confirmed by Dong’s algorithm calculations. The proposed method was validated and shown to be applicable for the determination of the three drugs in commercially available tablets. In addition, the impact of the method on the environment was assessed through four different analytical tools: National Environmental Methods Index, Analytical Eco-Scale, Green Analytical Procedure Index and Assessment of Green Profile. The proposed method was determined to be greener, with minimal impact on the environment with regard to waste production, energy consumption and use of hazardous chemicals.

Takotsubo syndrome (TTS) is an acute heart failure syndrome characterised by catecholamine-induced oxidative tissue damage. Punica granatum, a fruit-bearing tree, is known to have high polyphenolic content and has been proven to be a potent antioxidant. This study aimed to investigate the effects of pomegranate peel extract (PoPEx) pre-treatment on isoprenaline-induced takotsubo-like myocardial injury in rats. Male Wistar rats were randomised into four groups. Animals in the PoPEx(P) and PoPEx + isoprenaline group (P + I) were pre-treated for 7 days with 100 mg/kg/day of PoPEx. On the sixth and the seventh day, TTS-like syndrome was induced in rats from the isoprenaline(I) and P + I groups by administering 85 mg/kg/day of isoprenaline. PoPEx pre-treatment led to the elevation of superoxide dismutase and catalase (p < 0.05), reduced glutathione (p < 0.001) levels, decreased the thiobarbituric acid reactive substances (p < 0.001), H2O2, O2− (p < 0.05), and NO2− (p < 0.001), in the P + I group, when compared to the I group. In addition, a significant reduction in the levels of cardiac damage markers, as well as a reduction in the extent of cardiac damage, was found. In conclusion, PoPEx pre-treatment significantly attenuated the isoprenaline-induced myocardial damage, primarily via the preservation of endogenous antioxidant capacity in the rat model of takotsubo-like cardiomyopathy.

Background/Aim: Organophosphorus compounds (OP) bind to acetylcholinesterase (AChE) causing an irreversible inhibition of the enzyme. When doing in vivo studies of OP intoxication, to precisely measure AChE activity in the brain tissue it is necessary to remove as much blood from the brain as possible. By doing so, interference of the OPs present in the blood is avoided. Usually this demands expensive equipment, therefore, the aim of this study was to find a simple and economical method to eliminate the blood from brain blood vessels. Methods: Wistar albino rats were divided into four groups named Control (C), Control washout (CW), Paraoxon (Pox) and Paraoxon washout (PoxW) group. Rats in Pox and PoxW were treated with 0.25 mg/kg paraoxon subcutaneously (sc), while C and CW received 1 mL/kg sc saline instead. The "Marinković-Maksimović" ("MM") method was performed in rats from PoxW and CW groups. Activity of AChE was measured both in erythrocyte lysate and in brain tissue using spectrophotometry. Results: Macroscopic examination revealed that the elimination of blood was achieved in CW and PoxW groups. Activity of AChE in homogenised brain tissue was expectedly lower in the Pox and PoxW group, when compared to C and CW group, respectively. The CW group had a lower value of AChE activity in the brain tissue compared to C group, while activity of AChE in the PoxW group was statistically higher than in the Pox group (p = 0.044). Conclusion: The MM method provides good elimination of blood from the brain. Together with blood, present confounding factors that interfere with analysis in homogenised brain tissue, were also eliminated.