Repurposing the antimalarial chloroquine: a potential therapy for hepatic injury in a rat model of hindlimb ischemia–reperfusion by modulating apoptosis, autophagy, inflammation, and oxidative stress DOI Creative Commons

Miar M. Sherif,

Hanan S. El‐Abhar,

Hala M. Fawzy

et al.

Future Journal of Pharmaceutical Sciences, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 11, 2025

Abstract Background Besides its local injurious effect, hindlimb hypoxia/reperfusion (HL-H/R) can escalate leading to multiple organ dysfunction syndrome. Purpose of the study This explores chloroquine’s therapeutic potential in protecting liver tissue from collateral damage caused by HL-H/R, focusing on effects inflammation, oxidative stress, autophagy, and apoptosis. Methods results Male Wistar rats were apportioned into three distinct groups, control, HL-H/R model (90 min/8 days), + chloroquine (7 days). Western blot, ELISA, immunohistochemical, histopathology techniques revealed that post-administration an upturn architecture function. The antimalarial drug also abated hepatic content surrogate inflammatory marker TNF-α downregulated protein expression p -MAPK p38. was allied with a reduction NF-κB p65 transcription factor but increased anti-inflammatory interleukin (IL)-10. Moreover, amended interrupted redox balance reducing induced increase reactive oxygen nitrogen species. Chloroquine leveled off levels lipid peroxide MDA, DNA parameter 8-OHdG, as well NO while enhancing antioxidant capacity increasing TAC. These beneficial entailed inhibition apoptotic cell demise anti-apoptotic Bcl-2 markers Bax caspase-3. Finally, succeeded curbing autophagy process where it decreased Beclin-1 LC3-II, two autophagosome markers, along lysosomal cathepsin-D. Conclusion To recapitulate, improved remote actions (MAPK p38/NF-κB p65/TNF-α, IL-10) (MDA, NO, TAC) properties halting (Beclin-1, cathepsin-D) apoptosis (Bcl-2, Bax, caspase-3)-mediated death improve function (ALT, AST) structure.

Language: Английский

Repurposing the antimalarial chloroquine: a potential therapy for hepatic injury in a rat model of hindlimb ischemia–reperfusion by modulating apoptosis, autophagy, inflammation, and oxidative stress DOI Creative Commons

Miar M. Sherif,

Hanan S. El‐Abhar,

Hala M. Fawzy

et al.

Future Journal of Pharmaceutical Sciences, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 11, 2025

Abstract Background Besides its local injurious effect, hindlimb hypoxia/reperfusion (HL-H/R) can escalate leading to multiple organ dysfunction syndrome. Purpose of the study This explores chloroquine’s therapeutic potential in protecting liver tissue from collateral damage caused by HL-H/R, focusing on effects inflammation, oxidative stress, autophagy, and apoptosis. Methods results Male Wistar rats were apportioned into three distinct groups, control, HL-H/R model (90 min/8 days), + chloroquine (7 days). Western blot, ELISA, immunohistochemical, histopathology techniques revealed that post-administration an upturn architecture function. The antimalarial drug also abated hepatic content surrogate inflammatory marker TNF-α downregulated protein expression p -MAPK p38. was allied with a reduction NF-κB p65 transcription factor but increased anti-inflammatory interleukin (IL)-10. Moreover, amended interrupted redox balance reducing induced increase reactive oxygen nitrogen species. Chloroquine leveled off levels lipid peroxide MDA, DNA parameter 8-OHdG, as well NO while enhancing antioxidant capacity increasing TAC. These beneficial entailed inhibition apoptotic cell demise anti-apoptotic Bcl-2 markers Bax caspase-3. Finally, succeeded curbing autophagy process where it decreased Beclin-1 LC3-II, two autophagosome markers, along lysosomal cathepsin-D. Conclusion To recapitulate, improved remote actions (MAPK p38/NF-κB p65/TNF-α, IL-10) (MDA, NO, TAC) properties halting (Beclin-1, cathepsin-D) apoptosis (Bcl-2, Bax, caspase-3)-mediated death improve function (ALT, AST) structure.

Language: Английский

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