Hesperidin promotes lysosomal biogenesis in chronically ethanol‐induced cardiotoxicity in rats: A proposed mechanisms of protection

Abstract

Alcohol consumption is a major global risk factor for mortality and morbidity. We aimed to delineate the mechanisms underlying the potential ameliorative effects of hesperidin against chronically ethanol‐induced cardiotoxicity. Sixty male albino rats were divided into normal control group, hesperidin‐treated control group, untreated alcoholic group, and hesperidin‐treated alcoholic group. Transcription factor‐EB (TFEB) expression levels were estimated using real‐time reverse transcription‐polymerase chain reaction. Peroxisome proliferator–activated receptor γ coactivator 1‐α (PGC1‐α), macrophage inflammatory protein‐1 α, poly‐(ADP‐ribose)‐polymerase‐1 (PARP‐1) activity, and tenascin C levels in cardiac tissues were estimated by enzyme‐linked immunosorbent assay; while tissue malondialdehyde and total antioxidant capacity were evaluated spectrophotometrically. Our data portrayed promoting lysosomal biogenesis, as judged by upregulation of TFEB expression and its target PGC1‐α, as well as decreased PARP‐1 activity and offsetting inflammation, oxidative stress, and tissue injury as the principal culprits mediating the cardioprotective effect of hesperidin in alcohol‐induced cardiotoxicity. In conclusion, hesperidin can be used as a cardioprotective agent in chronically ethanol‐induced cardiotoxicity.

Hesperidin protects against the chlorpyrifos‐induced chronic hepato‐renal toxicity in rats associated with oxidative stress, inflammation, apoptosis, autophagy, and up‐regulation of PARP‐1/VEGF

“…This result shows that CPF toxication causes DNA damage in hepatocytes and renal tubular cells, while HSP can play a protective role in CPF-induced hepatorenal toxicity by reducing PARP-1 and 8-OHdG activation. In another study that supports this interpretation of the effects of HSP, the administration of HSP has played a protective role on DNA damage by reducing PARP-1 activation in chronic ethanol-induced rats with cardiotoxicity 67. In light of the data obtained, CPF residues, which are frequently used in agricultural areas, pose a great danger to humans and animals.…”

Vascular injury associated with ethanol intake is driven by AT1 receptor and mitochondrial dysfunction

“…PGC-1α is one of the main transcription factors responsible for stimulating mitochondrial biogenesis, a process that involves the formation of new mitochondria by adding proteins and membranes to pre-existing mitochondria 71 . Some studies have shown that ethanol consumption reduces the phosphorylation of cAMP-response element binding protein (p-CREB) in cardiac tissue 72 and neuronal cells 73 . CREB is the main transcription factor that regulates the transcription of the PGC-1α gene 74 .…”

Hesperidin Alleviates Hepatic Injury Caused by Deoxynivalenol Exposure through Activation of mTOR and AKT/GSK3β/TFEB Pathways

“…Transcription factor EB (TFEB) is a transcriptional regulator that plays an important role in the control of autophagy and lysosomal development . In a chronic ethanol-induced rat model, HDN exhibited the ability to upregulate TFEB expression and promote lysosomal biogenesis . Therefore, we hypothesized that HDN may be closely related to the regulation of autophagy and lysosomal function.…”