Tadalafil in Increasing Doses: The Influence on Coronary Blood Flow and Oxidative Stress in Isolated Rat Hearts

Pharmacology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Nada M. Banjac ◽  
Velibor M. Vasović ◽  
Nebojša P. Stilinović ◽  
Dušan V. Prodanović ◽  
Ana D. Tomas Petrović ◽  
...  

<b><i>Introduction:</i></b> This study aimed to assess the influence of different doses of tadalafil on coronary flow and oxidative stress in isolated rat hearts. <b><i>Methods:</i></b> The hearts of male Wistar albino rats (<i>n</i> = 48) were retrogradely perfused according to the Langendorff technique at gradually increased constant perfusion pressure (CPP) (40–120 mm Hg). Coronary flow and oxidative stress markers: nitrite oxide (NO) outflow and superoxide anion production in coronary effluent were measured. The experiments were performed during control conditions and in the presence of tadalafil (10, 20, 50, and 200 nM) alone or with Nω-nitro-L-arginine monomethyl ester (L-NAME) (30 μM). <b><i>Results:</i></b> Tadalafil administration significantly increased coronary flow at all CPP values at all administered doses. Tadalafil led to an increase in the NO levels, but a statistically significant NO release increase was found only at the highest dose and highest CPP. Tadalafil did not significantly affect the release of O<sup>2−</sup>. After inhibiting the nitrite oxide synthase system by L-NAME, tadalafil-induced changes in cardiac flow and NO levels were reversed. L-NAME administration had no pronounced effect on the O<sup>2−</sup> release. <b><i>Conclusion:</i></b> Tadalafil causes changes in the heart vasculature in a dose-dependent manner. It does not lead to a significant increase in the production of superoxide anion radicals.

2015 ◽  
Vol 16 (4) ◽  
pp. 297-304
Author(s):  
Tanja Sobot ◽  
Amela Matavulj ◽  
Vladimir Jakovljevic ◽  
Tamara Nikolic ◽  
Vladimir Zivkovic ◽  
...  

AbstractThe aim of this experimental study was to assess the effects of the acute administration of L-arginine alone and in combination with L-NAME (a non-selective NO synthase inhibitor) on the coronary flow and oxidative stress markers in isolated rat hearts. The experimental study was performed on hearts isolated from Wistar albino rats (n=12, male, 8 weeks old, body mass of 180-200 g). Retrograde perfusion of the isolated preparations was performed using a modified method according to the Langendorff technique with a gradual increase in the perfusion pressure (40–120 cmH2O). The following values were measured in the collected coronary effluents: coronary flow, released nitrites (NO production marker), superoxide anion radical and the index of lipid peroxidation (measured as thiobarbiturate reactive substances). The experimental protocol was performed under controlled conditions, followed by the administration of L-arginine alone (1 mmol) and L-arginine (1 mmol) + L-NAME (30 μmol). The results indicated that L-arginine did not significantly increase the coronary flow or the release of NO, TBARS and the superoxide anion radical. These effects were partially blocked by the joint administration of L-arginine + L-NAME, which indicated their competitive effect. Hence, the results of our study do not demonstrate significant effects of L-arginine administration on the coronary flow and oxidative stress markers in isolated rat hearts.


2014 ◽  
Vol 15 (1) ◽  
pp. 11-19 ◽  
Author(s):  
Maja Jevdjevic ◽  
Ivan Srejovic ◽  
Vladimir Zivkovic ◽  
Nevena Barudzic ◽  
Anica Petkovic ◽  
...  

ABSTRACT Eicosanoids lead to the promotion of inflammation, cause fever and pain and have many other eff ects. NSAIDs block the action of cyclooxygenase (COX) during the process of converting arachidonic acid into inflammatory mediators, thus reducing the symptoms of inflammation. Investigations focusing on nonselective COX inhibitors, used in high doses, revealed harmful eff ects on myocardial function. Th e aim of our study was to assess the eff ects of two nonselective NSAIDs, diclofenac and ibuprofen, on cardiodynamic parameters, coronary flow and oxidative stress biomarkers in isolated rat hearts. Th e hearts of male Wistar albino rats were excised and retrogradely perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40-120 cm H2O). Th e experiments were performed under controlled conditions (Krebs-Henseleit physiological solution). Th e hearts were perfused with 10 μmol/l diclofenac and 10 μmol/l ibuprofen. Th e heart function parameters, including the maximum rate of pressure development (dp/dt max), minimum rate of pressure development (dp/dt min), systolic left ventricular pressure (SLVP), diastolic left ventricular pressure (DLVP), mean perfusion pressure (MBP) and heart rate (HR), were continuously registered. Coronary flow (CF) was measured flowmetrically. Oxidative stress markers, including the index of lipid peroxidation measured as TBARS, nitric oxide measured through nitrites (NO2 -), superoxide anion radical (O2 -), and hydrogen peroxide (H2O2) in the coronary venous effluent, were assessed spectrophotometrically. Our results showed that diclofenac aff ected cardiodynamic parameters more significantly than did ibuprofen. Furthermore, the present data indicate that both estimated COX inhibitors do not promote the production of reactive oxygen species.


2017 ◽  
Vol 29 (7) ◽  
pp. 1415 ◽  
Author(s):  
Shauna A. Holden ◽  
Craig Murphy ◽  
Juan F. Moreno ◽  
Stephen T. Butler ◽  
Andrew R. Cromie ◽  
...  

This study sought to compare the in vitro characteristics of fresh and frozen non-sorted (NS) and sex-sorted (SS) bull spermatozoa. Experiment 1: Holstein–Friesian ejaculates (n = 10 bulls) were split across four treatments and processed: (1) NS fresh at 3 × 106 spermatozoa, (2) X-SS frozen at 2 × 106 spermatozoa, (3) X-SS fresh at 2 × 106 spermatozoa and (4) X-SS fresh at 1 × 106 spermatozoa. NS frozen controls of 20 × 106 spermatozoa per straw were sourced from previously frozen ejaculates (n = 3 bulls). Experiment 2: Aberdeen Angus ejaculates (n = 4 bulls) were split across four treatments and processed as: (1) NS fresh 3 × 106 spermatozoa, (2) Y-SS fresh at 1 × 106 spermatozoa, (3) Y-SS fresh at 2 × 106 spermatozoa and (4) X-SS fresh at 2 × 106 spermatozoa. Controls were sourced as per Experiment 1. In vitro assessments for progressive linear motility, acrosomal status and oxidative stress were carried out on Days 1, 2 and 3 after sorting (Day 0 = day of sorting. In both experiments SS fresh treatments had higher levels of agglutination in comparison to the NS fresh (P < 0.001), NS frozen treatments had the greatest PLM (P < 0.05) and NS spermatozoa exhibited higher levels of superoxide anion production compared with SS spermatozoa (P < 0.05). Experiment 1 found both fresh and frozen SS treatments had higher levels of viable acrosome-intact spermatozoa compared with the NS frozen treatments (P < 0.01).


2016 ◽  
Vol 73 (1) ◽  
pp. 141-153 ◽  
Author(s):  
Isidora Stojic ◽  
Ivan Srejovic ◽  
Vladimir Zivkovic ◽  
Nevena Jeremic ◽  
Marko Djuric ◽  
...  

2006 ◽  
Vol 93 (4) ◽  
pp. 251-261 ◽  
Author(s):  
VLj Jakovljevic ◽  
VLj Jakovljevic ◽  
PS Canovic ◽  
PS Canovic ◽  
PS Canovic ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Vladimir Zivkovic ◽  
Vladimir Jakovljevic ◽  
Olga Pechanova ◽  
Ivan Srejovic ◽  
Jovana Joksimovic ◽  
...  

Considering the adverse effects of DL-homocysteine thiolactone hydrochloride (DL-Hcy TLHC) on vascular function and the possible role of oxidative stress in these mechanisms, the aim of this study was to assess the influence of DL-Hcy TLHC alone and in combination with specific inhibitors of important gasotransmitters, such as L-NAME, DL-PAG, and PPR IX, on cardiac contractility, coronary flow, and oxidative stress markers in an isolated rat heart. The hearts were retrogradely perfused according to the Langendorff technique at a 70 cm H2O and administered 10 μM DL-Hcy TLHC alone or in combination with 30 μM L-NAME, 10 μM DL-PAG, or 10 μM PPR IX. The following parameters were measured:dp/dtmax,dp/dtmin, SLVP, DLVP, MBP, HR, and CF. Oxidative stress markers were measured spectrophotometrically in coronary effluent through TBARS, NO2,O2-, and H2O2concentrations. The administration of DL-Hcy TLHC alone decreaseddp/dtmax, SLVP, and CF but did not change any oxidative stress parameters. DL-Hcy TLHC with L-NAME decreased CF,O2-, H2O2, and TBARS. The administration of DL-Hcy TLHC with DL-PAG significantly increaseddp/dtmax but decreased DLVP, CF, and TBARS. Administration of DL-Hcy TLHC with PPR IX caused a decrease indp/dtmax, SLVP, HR, CF, and TBARS.


2020 ◽  
Vol 21 (3) ◽  
pp. 91-98
Author(s):  
Mohamed Abomosallam ◽  
Mahmoud Elalfy ◽  
Fathy Sleem

Objective: To evaluate the postnatal toxicity of copper oxychloride (COC) in lactating female albino rats. Design: Randomized controlled experimental study. Animals: Eighteen pregnant female albino rats weight 150±10 g and 6-7 week old. Procedures: Eighteen pregnant female albino rats were divided into 3 groups treated orally with copper oxychloride 0, 73.5, 147 mg/kg (equivalent 1/20 and 1/10 of LD50) daily from first day of parturition for 21 days. Female rats and its offspring were euthanized at 21 days of treatment. The postnatal toxic effect in the neonates and dams were estimated through biochemical biomarkers as metabolic and oxidative stress biomarkers, histopathological and hematological evaluation. Results: There was a significant increase in liver enzymes activities as ALT and GGT and oxidative stress biomarker as MDA (P < 0.05) in both suckling pups and lactating dams beside decrease the level of metabolic biomarkers as glucose, total protein and cholesterol (P < 0.05). Additionally, antioxidant enzymes as SOD and CTA (P < 0.05) were reduced significantly in the treated groups in a dose dependent manner in comparison to control group. Moreover the histopathological revealed that Dams treated with COC at both doses shown degenerative changes and intralobular histiocytic infiltration with intralobular fibroblastic proliferation in the hepatic tissue. Neuronal necrosis, neuronophagia and astrocytosis in the brain tissue with degenerative changes of purkinje cells in cerebellum. Fibrous tissue proliferation of renal glomeruli with degenerative changes in renal tubular epithelium and marked lymphoid depletion in the splenic tissue in dose dependent manner. While Suckling pups of treated dams with different doses of COC shown focal histiocytic and lymphocytic infiltration besides congestion of portal vein and margination of leukocytes, focal edema in the neuropils with focal hemorrhagic areas in the brain tissue, degeneration in the renal glomeruli and severe lymphoid depletion with congestion of the splenic sinusoids in dose dependent manner. Conclusion and clinical relevance: The potential postnatal toxic effect of copper oxychloride in neonates and lactating female albino rats through transmammary transmission in milk clarified from biochemical and histopathological evaluation of dams and its pups.


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