Exploratory study of β-endorphin, immune profiles, and skeletal muscle endoplasmic reticulum stress following an overtraining-like forced swimming regimen in rats

Siswanto, Ferbian Milas and Abigail, Periskila and Elvandari, Amanda Putri and Pangkahila, Alex (2026) Exploratory study of β-endorphin, immune profiles, and skeletal muscle endoplasmic reticulum stress following an overtraining-like forced swimming regimen in rats. PHYSIOLOGY INTERNATIONAL, 113 (3). pp. 443-456. ISSN 2498-602X

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Abstract

Introduction: Physical exercise triggers wide range of physiological responses, including immunological and neuroendocrine alterations. Although moderate exercise is beneficial, overtraining may cause various detrimental effects. Objective: To assess the effects of overtraining-like forced exercise on beta-endorphin levels, immune modulation, and endoplasmic reticulum (ER) stress in rats. Methodology: Twenty-one male Wistar rats were randomly divided into three groups: negative control (NC) group (without any training program), moderate exercise (ME) group (30 min of swimming, 3 times a week for 4 weeks) and overtraining-like forced exercise (OT) group (60 min of swimming, 7 times a week for 4 weeks). Plasma levels of β-endorphin, corticosterone, and cytokines (IL-6, TNF-α, IL-10), as well as skeletal muscle ER stress markers (GRP78 and CHOP), were measured using ELISA. Total and differential leukocyte counts were analyzed with an automated hematology analyzer. Results: The extensive training protocol in the OT group increased plasma beta-endorphin levels (P < 0.05), depleted leukocyte counts and differentials (P < 0.05)and altered cytokines profile (P < 0.05). The GRP78/CHOP ratio revealed a significant depletion in the OT group compared to the NC (P < 0.05), indicating ER stress activation. Discussion: Elevated betaendorphin reflects a neuroendocrine stress response that may become maladaptive over time. The observed immune dysregulation and increased ER stress suggest that overtraining-like forced exercise imposes a physiological burden potentially leading to tissue dysfunction and inflammation. Conclusions: Prolonged overtraining-like forced exercise, if not properly regulated, may lead to maladaptive stress responses and adverse health outcomes.

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