Investigating systemic effects of chronic stress on hepatic and cardiac tissue in female Wistar rats

Chronic psychosocial stress contributes to cardiometabolic disease onset and progression through various mechanisms including through HPA-axis dysregulation, inflammation, oxidative stress, and autophagic impairment. Growing evidence suggests females may be disproportionately vulnerable to these effects, yet mechanistic insight is lacking. This study investigated these molecular mechanisms within female Wistar rat cardiac and hepatic tissues collected from a chronic restraint stress (CRS) parent study. Snap-frozen cardiac and hepatic tissues from female Wistar rats exposed to 28 days of CRS (n=8) or control conditions (n=8) were analysed. Redox balance was assessed via antioxidant assays (superoxide dismutase [SOD], catalase, and ORAC) and oxidative damage marker (malondialdehyde adducts) in whole-cell lysates and subcellular fractions. Autophagy-related proteins (p62, LC3B, Beclin-1, SNAP29, SOD1/2) were quantified by Western blotting. CRS induced mild oxidative damage restricted to cardiac tissue, with reduced SOD activity and elevated compartmental malondialdehyde, while hepatic redox parameters remained unaltered. Whole-cell autophagy markers were stable in both organs. Subcellular analyses, limited by crude fractions from snap-frozen tissue, revealed innate organ differences preserved under CRS: liver displaying higher heavy-membrane recovery of LC3B-II and SNAP29, consistent with its greater constitutive autophagic activity. The heart exhibited no such enrichment and no CRS-induced autophagic response. Females showed effective short-term redox protection under chronic stress but display organ-specific vulnerabilities. The liver’s robust basal autophagy enhances resilience, whereas the heart’s lower activity may predispose it to cumulative damage. These findings emphasise the need for female-inclusive stress research and suggest sex-specific therapies targeting autophagic competence in stress-related cardiometabolic disease.

Grantor dc:publisher

Stellenbosch : Stellenbosch University

Year dc:date.issued

2026

Author dc:creator

• Andrews, Jasmine Cameron

Advisors dc:contributor.advisor

• Essop, Faadiel
• Joseph, Danzil
• Cairns, Megan

Language dc:language.iso

en

Repository record dc:identifier.uri

https://scholar.sun.ac.za/handle/10019.1/135552

OAI identifier oai:identifier

oai:scholar.sun.ac.za:10019.1/135552