Expression of adenosine receptors and vegf during angiogenesis and its inhibition by pentoxifylline—A study using zebrafish model

Nathan, Jhansi; Lakshmanan, Ganesh; Prakash, Seppan; Malathi, R.

doi:10.1016/j.biopha.2016.10.045

Cited by 29 publications

(22 citation statements)

References 33 publications

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“…Treating zebrafish embryos with an adenosine analogue NECA (50-N-ethylcarboxamidoadenosine) for 72 h increases blood vessel formation compared with control embryos. [20,21] Similarly, it has been shown that NECA enhances angiogenesis and neovascularization in transplanted human ovarian tissue in comparison with control group. [22] Moreover, Koszalka et al [23] showed that CCPA, CGS-21680 and IB-MECA, specific agonists of A1, A2 and A3 ARs, respectively, significantly inhibited B16F10 melanoma growth in CD73 knockout mice in early stage.…”

Section: Role Of Adenosine In Angiogenesismentioning

confidence: 95%

“…Adenosine is a key regulator of angiogenesis. Treating zebrafish embryos with an adenosine analogue NECA (50‐N‐ethylcarboxamidoadenosine) for 72 h increases blood vessel formation compared with control embryos . Similarly, it has been shown that NECA enhances angiogenesis and neovascularization in transplanted human ovarian tissue in comparison with control group .…”

Section: Role Of Adenosine In Angiogenesismentioning

confidence: 95%

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Therapeutic potency of pharmacological adenosine receptor agonist/antagonist in angiogenesis, current status and perspectives

Bahreyni

Khazaei

Rajabian

et al. 2017

Journal of Pharmacy and Pharmacology

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Objectives Adenosine concentration significantly increases in tumour microenvironment contributing to tumorigenic processes including cell proliferation, survival, invasion and of special interest in this review angiogenesis. Key findings This review summarizes the role of pharmacological adenosine receptor agonist and antagonist in regulating angiogenesis for a better understanding and hence a better management of angiogenesis-associated disorders. Summary Depending upon the pharmacological characteristics of adenosine receptor subtypes, adenosine elicits anti-or pro-angiogenic responses in stimulated cells. Inhibition of the stimulatory effect of adenosine signalling on angiogenesis using specific pharmacological adenosine receptor agonist, and antagonist is a potentially novel strategy to suppress angiogenesis in tumours.

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Section: Role Of Adenosine In Angiogenesismentioning

confidence: 95%

Section: Role Of Adenosine In Angiogenesismentioning

confidence: 95%

Therapeutic potency of pharmacological adenosine receptor agonist/antagonist in angiogenesis, current status and perspectives

Bahreyni

Khazaei

Rajabian

et al. 2017

Journal of Pharmacy and Pharmacology

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“…Embryos were carefully transferred to a 10cm diameter petri dishes using Pasteur pipette and were washed twice with chlorine free water, to remove the debris and other dust particles to avoid infection. 28 A total of ~ 1000-1200 embryo were collected. Embryos were then segregated into 6 well culture plates (20embryos/well).…”

Section: Embryo Collectionmentioning

confidence: 99%

Raw turmeric and pure curcumin: a comparison of embryonic cytotoxicity in zebrafish

Rajagopal

Meenakshi

Kalyanaraman

2017

Int J Basic Clin Pharmacol

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Background: Turmeric (Curcuma longa) is widely used in ayurveda and siddha formulations for treating various ailments. This study compares the gross effects of curcumin and natural state turmeric on zebrafish embryos.Methods: Turmeric powder and curcumin were used in this study. Zebrafish embryos were treated with different concentration of both turmeric and curcumin to evaluate their gross effects including toxicity. Morphological variations including hatching, survival, heart rates, head width, eye width, tail width and yolk sac area were examined by stereomicroscope.Results: Embryos treated with curcumin or raw turmeric with concentration of 27.628 and 36.83µg/ml exhibited a reduction of survival rates (15-20%) at 24, 48 and 72hpf. Turmeric treated embryos had near normal hatching rates when compared to curcumin treated embryos at 48hpf whereas decreased hatching rate was observed in turmeric treated groups at 72hpf when compared to curcumin treated group. No significant morphological anomaly in head /eye / tail width, length of yolk sac and average embryo length were witnessed among all the 3 groups. The toxicity assays revealed various morphological deformities in embryos treated with different concentrations of both turmeric and curcumin.Conclusions: Zebrafish embryos treated with increasing concentrations of curcumin in pure form or raw turmeric exhibited similar morphometric and toxic effects indicating that raw turmeric could elicit anti cancer activity with similar potency as that of active ingredient curcumin due to their toxicity attribute. It may be beneficial to explore the negative attributes of such common natural food ingredients that may be beneficial for therapeutic interventions.

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“…Human and animal studies have shown that most of the methylxanthines increases the heart rate [ 10 , 13 , 15 , 35 , 40 , 41 ], whereas doxofylline does not have any effect on it [ 10 , 36 , 42 , 43 ]. These findings were similar to the results we obtained in the zebrafish embryos where all the methylxanthines increased the heart rate and doxofylline did not have any effect.…”

Section: Discussionmentioning

confidence: 99%

Methylxanthines induce structural and functional alterations of the cardiac system in zebrafish embryos

Basnet

Zizioli

Guarienti

et al. 2017

BMC Pharmacol Toxicol

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BackgroundZebrafish embryos are emerging as a model for pharmacological and toxicological studies. We used zebrafish embryos to study the general toxicity and cardiovascular effects of eight methylxanthines: aminophylline, caffeine, diprophylline, doxofylline, etophylline, 3-isobutyl-1-methylxanthine (IBMX), pentoxifylline and theophylline.MethodsMicroinjections of the eight methylxanthines were performed in 1-2 cell stage zebrafish embryos and the general toxicity and cardiovascular effects were analyzed at different time points. Embryotoxicity and teratogenicity were evaluated to understand the general toxicity of these compounds. Structural and functional alterations of the heart were evaluated to assess the cardiovascular effects.ResultsOur results showed different activity patterns of the methylxanthines drugs. Caffeine, IBMX, pentoxifylline and theophylline were highly embryotoxic and teratogenic; aminophylline, doxofylline and etophylline were embryotoxic and teratogenic only at higher doses, and diprophylline showed a minimal (<10%) embryotoxicity and teratogenicity. Most of these drugs induced structural alteration of the heart in 20-40% of the injected embryos with the maximum dose. This structural alteration was fatal with the embryos ultimately dying within 120 hpf. All the drugs induced a transient increase in heart rate at 48 hpf which returned to baseline within 96 hpf. This functional effect of methylxanthines showed similarity to the studies done in humans and other vertebrates.ConclusionOur results indicate the potential toxicity and teratogenicity of different methylxanthines in the embryos during embryonic development, the most sensitive period of life. Although interspecies differences need to be considered before drawing any conclusion, our study elucidated that a single exposure of methylxanthines at therapeutic range could induce cardiac dysfunction besides causing embryotoxicity and teratogenicity. Of all the drugs, diprophylline appeared to be safer, with lower degree of embryotoxicity, teratogenicity and cardiac toxicity as compared to other methylxanthines.Electronic supplementary materialThe online version of this article (10.1186/s40360-017-0179-9) contains supplementary material, which is available to authorized users.

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Expression of adenosine receptors and vegf during angiogenesis and its inhibition by pentoxifylline—A study using zebrafish model

Cited by 29 publications

References 33 publications

Therapeutic potency of pharmacological adenosine receptor agonist/antagonist in angiogenesis, current status and perspectives

Therapeutic potency of pharmacological adenosine receptor agonist/antagonist in angiogenesis, current status and perspectives

Raw turmeric and pure curcumin: a comparison of embryonic cytotoxicity in zebrafish

Methylxanthines induce structural and functional alterations of the cardiac system in zebrafish embryos

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