The Highest Battlefield of the World : Medical Problems and Solutions

Jindal, A.K.

doi:10.1016/s0377-1237(09)80135-4

Cited by 9 publications

(2 citation statements)

References 3 publications

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“…The normoxic conditions were maintained at 21% and hypoxic conditions maintained at 10%. 15,16 Platelets were visualized under inverted microscope before further experimentation.…”

Section: Methodsmentioning

confidence: 99%

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Chloroquine attenuates hypoxia-mediated autophagy to curb thrombosis- anex vivoandin vivostudy

Bandyopadhyay,

Katakia,

Mukherjee

et al. 2024

Preprint

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Background: Hypoxia can trigger the activation of blood platelets, leading to thrombosis. If not addressed clinically, it can cause severe complications and fatal consequences as well. The current treatment regime for thrombosis is often palliative and includes long-term administration of anticoagulants, which has the risk of over-bleeding in injury and other secondary effects as well. This demands a deeper understanding of the process and exploration of an alternative therapeutic avenue. Interestingly, recent studies demonstrate that platelets though atypical and enucleated, possess components of autophagy machinery. This cellular homeostatic process though well-studied in non-platelet cells, is under-explored in platelets. Methods: In this study, we report an activation of autophagy in rat-derived platelets cultured under physiologically relevant hypoxic condition (10% O2) ex vivo. Furthermore, autophagy was triggered in vivo when rats were exposed to hypobaric hypoxic conditions. Subsequently, restriction or surgical ligation of the inferior vena cava (IVC) was performed to induce thrombus formation. Post confirming the impact of autophagy induction on platelet functioning, it was inhibited, and then platelet activation and aggregation status were evaluated using light transmission aggregometry, flow cytometry, immunofluorescence and immunoblotting. Results: Herein, we show that autophagy inhibition with the potent autophagy inhibitor- CQ, a repurposed FDA-approved drug, can significantly reduce platelet activation, both in ex vivo and in vivo settings. CQ withdrawal reversed the phenomenon indicating a dynamic effect. Thereafter, in flow restriction or surgical ligation model, interestingly, CQ-pre-treated rats showed reduced clotting ability. Importantly, CQ at the stipulated dose was found to be non-toxic to the tissues, as analyzed through histological staining. Conclusion: Thus, we propose that the repurpose of the FDA approved drug CQ can attenuate hypoxia-induced thrombosis through inhibition of autophagy and can be explored as an effective therapeutic alternative.

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“…The normoxic conditions were maintained at 21% and hypoxic conditions maintained at 10%. 15,16 Platelets were visualized under inverted microscope before further experimentation.…”

Section: Methodsmentioning

confidence: 99%

“…The copyright holder for this preprint (which this version posted April 27, 2024. ; https://doi.org/10.1101/2024.04.23.590850 doi: bioRxiv preprint conditions maintained at 10%. 15,16 Platelets were visualized under inverted microscope before further experimentation.…”

Section: Ex-vivo Exposure Of Platelets To Hypoxiamentioning

confidence: 99%