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

и другие.

Future Journal of Pharmaceutical Sciences, Год журнала: 2025, Номер 11(1)

Опубликована: Март 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.

Язык: 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

и другие.

Future Journal of Pharmaceutical Sciences, Год журнала: 2025, Номер 11(1)

Опубликована: Март 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.

Язык: Английский

Процитировано

0