Experimental Physiology最新文献

{"title":"The physiology of survival: From the third man to placebo escape hatch?","authors":"Frank E. Marino, Alexander F. Marino","doi":"10.1113/EP094011","DOIUrl":"10.1113/EP094011","url":null,"abstract":"<p>During his 1916 Antarctic crossing of South Georgia, Shackleton later described the persistent sensation that his small group was not alone (Shackleton, <span>1919</span>). Despite there being only three men present, each independently reported the feeling of a fourth companion travelling beside them. Shackleton himself reflected that during the crossing ‘it seemed to me often that we were four, not three’ (Geiger, <span>2009</span>; Shackleton, <span>1919</span>: p. 211). Similar experiences have since been described by mountaineers, sailors, polar explorers, soldiers, disaster survivors and endurance athletes operating under extreme fatigue, isolation, hypoxia, fear and environmental stress (Suedfeld & Mocellin, <span>1987</span>). This phenomenon was later described as a ‘sensed presence’ (Suedfeld & Mocellin, <span>1987</span>), noting that such experiences commonly emerge in extreme or unusual environments involving prolonged isolation, monotony, physical stress and environmental threat. In his compelling and classic text, John Geiger (<span>2009</span>), termed this phenomenon the ‘third man factor’, proposing that in conditions of extreme threat the human brain might generate a reassuring presence that sustains agency, hope and survival-oriented behaviour.</p><p>Such accounts emerge near what have been described as ‘the precipice of thermoregulatory failure’, where survival depends upon the robustness of integrative physiological responses operating close to the limits of homeostasis (Kenney et al., <span>2004</span>). Yet, physiology might be less about the passive encounter of biological limits and more about the active regulation of behaviour before those limits are even reached (Ulmer, <span>1996</span>). Human tolerance to extreme heat, dehydration, hypoxia, exhaustion and environmental uncertainty is not determined simply by isolated physiological capacities, but by anticipatory systems that continuously adjust effort, pacing, perception and decision-making to preserve survival (Marino, <span>2004</span>).</p><p>From this perspective, the ‘third man’ might represent more than a perceptual distortion or cognitive suspension of disbelief. Importantly, and as previously argued, a sensed presence should not necessarily be viewed as psychopathology but might instead represent a normal adaptive response to unusual environments and that ‘Students of the presence phenomenon … usually fail to consider that it may be an adaptive response, a normal reaction to an abnormal situation’;a regulatory phenomenon that preserves agency, suppresses despair and maintains purposeful behaviour when the alternative might be behavioural withdrawal or homeostatic catastrophe. In such conditions, perception itself becomes physiologically relevant (Marcora & Staiano, <span>2010</span>; Suedfeld & Mocellin, <span>1987</span>: p. 49). The conjuring of a reassuring presence under extreme threat might itself represent an extension of survival phy","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"111 10","pages":"4262-4265"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevation of body temperature during exercise enhances protection against dexamethasone‑induced skeletal muscle atrophy.","authors":"Berkay Ozerklig, Senay Akin, Seda Olgaz Bingol, Bulent Okan Yildiz, Scott K Powers, Ibrahim Turkel, Haydar A Demirel","doi":"10.1113/EP093744","DOIUrl":"10.1113/EP093744","url":null,"abstract":"<p><p>Prolonged glucocorticoid exposure induces skeletal muscle atrophy through suppression of protein synthesis and activation of catabolic signalling pathways. Although exercise attenuates glucocorticoid-induced muscle loss, whether exercise-induced increases in body temperature contribute remains unclear. In this study, we examined whether exercise in different thermal conditions modulates skeletal muscle atrophy and intracellular signalling during glucocorticoid exposure. Female Sprague-Dawley rats (n = 48) were assigned to six groups: control (CON), dexamethasone-treated (DEX), cold exercise (∼5°C; CE), cold exercise with dexamethasone (CED), warm exercise (25°C; WE) and warm exercise with dexamethasone. Exercise protocols were matched, and dexamethasone was administered for 5 days. Dexamethasone reduced plantaris muscle mass (by 17%, P < 0.0001) and fibre cross-sectional area (27%, P < 0.0001). During dexamethasone treatment, exercise in a cold environment provided partial protection, with muscle mass higher than DEX (P = 0.0476), but both muscle mass and fibre CSA remained lower than CON (P = 0.0096 and P = 0.0215, respectively). In contrast, exercise in a warm environment preserved muscle mass and fibre CSA (no difference vs. CON) and resulted in higher muscle mass (P = 0.0070) and fibre CSA (P < 0.0001) than DEX. Exercise-induced increases in rectal temperature were associated with higher Hsp72 and Hsp25 expression, partial preservation of Akt-FoxO3a signalling and reduced MuRF1 expression, whereas exercise in a cold environment showed minimal heat shock protein response and limited suppression of catabolic signalling. These findings indicate that exercise-induced elevation of body temperature enhances protection against glucocorticoid-induced skeletal muscle atrophy and support a role for heat-associated cellular stress responses in modulating muscle protein turnover during glucocorticoid exposure.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4781-4792"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13524206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: Surgery in Space: The Ultimate Frontier.","authors":"","doi":"10.1113/eph.70449","DOIUrl":"10.1113/eph.70449","url":null,"abstract":"<p><strong>Retraction: </strong>M. Bashir, A. Murtada, M. Jubouri, A. Bashir, I. Williams, and D. Bailey, \"Surgery in Space: The Ultimate Frontier,\" Experimental Physiology (2025): EP092765, 10.1113/EP092765. The above article, published online on 10 June 2025 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by the Physiological Society and John Wiley & Sons Ltd., with the agreement of all authors. Following publication, concerns were raised by a third party that one of the references in the article could not be verified. A subsequent investigation by the editors found that 12 out of 23 citations could not be substantiated as they were presented in the published article. As a result, The Physiological Society and John Wiley & Sons Ltd no longer have confidence in the article as a properly supported scholarly contribution and therefore agree that the article must be retracted.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4942"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13489105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-frequency characteristics of scalp high-frequency oscillations provide complementary biomarkers in infantile epileptic spasms syndrome.","authors":"Shunta Yamaguchi, Keisuke Maeda, Naoko Ishihara, Gen Furukawa, Himari Tsuboi, Keisuke Osakabe, Keiko Sugimoto, Naohiro Ichino","doi":"10.1113/EP094250","DOIUrl":"10.1113/EP094250","url":null,"abstract":"<p><p>Infantile epileptic spasms syndrome (IESS) is characterized by epileptic spasms (ES) in infants and hypsarrhythmia on EEG. High-frequency oscillations (HFOs), defined as oscillatory events at >80 Hz, reflect rapid spatiotemporal dynamics of cortical activity and might serve as novel biomarkers for epilepsy. In this study, we investigated the association among hypsarrhythmia, ES and scalp HFOs in IESS, focusing on their spatiotemporal and morphological characteristics. We analysed scalp EEG recordings from 22 paediatric patients with IESS (12 males; age range, 0-12 years), classified into four groups: hypsarrhythmia with ES; hypsarrhythmia without ES; multifocal interictal epileptiform discharges (IED); and non-multifocal IED. The proportions of EEG recordings with at least one detected scalp HFO differed significantly among the groups, being 100.0% in hypsarrhythmia with ES, 90.9% in hypsarrhythmia without ES, 36.0% in multifocal IED and 29.4% in non-multifocal IED (P < 0.001). Age-adjusted odds ratios [95% confidence intervals] for high HFO detection rates were significantly greater in the hypsarrhythmia groups than in the IED groups (with ES, 24.66 [4.86-125.10], P < 0.001; and without ES, 8.38 [1.94-36.20], P = 0.004). Receiver operating characteristic analysis showed that scalp HFO detection rates discriminated ES activity with an area under the curve of 0.92, 100% sensitivity and 77.4% specificity. Compared with the IED groups, the hypsarrhythmia groups exhibited lower-frequency HFOs, with the lowest HFO frequencies being observed in the hypsarrhythmia with ES group. These findings suggest that the spatiotemporal and morphological characteristics of scalp HFOs might provide complementary multidimensional biomarkers for hypsarrhythmia and assessing ictal states in IESS.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4852-4875"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13495046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sirtuin signalling governs calcium homeostasis and mitochondrial function in metabolic syndrome cardiomyocytes.","authors":"Firat Akat, Leila Aryan, Suatnur Şık, Erkan Tuncay","doi":"10.1113/EP094062","DOIUrl":"10.1113/EP094062","url":null,"abstract":"<p><p>Metabolic syndrome (MetS) is a major contributor to cardiovascular disease and is characterized by impaired Ca²⁺ handling and mitochondrial dysfunction in cardiomyocytes. However, the upstream mechanisms linking metabolic stress to these alterations remain incompletely defined. Here, we investigated whether sirtuin signalling coordinates intracellular Ca²⁺ homeostasis and mitochondrial function in a high-sucrose diet-induced mouse model of MetS. Male BALB/c mice were exposed to 32% sucrose for 24 weeks, followed by isolation of ventricular cardiomyocytes. MetS cardiomyocytes exhibited mitochondrial depolarization, increased reactive oxygen species production, elevated basal cytosolic Ca²⁺ levels, reduced Ca²⁺ transient amplitude and decreased sarcoplasmic reticulum Ca²⁺ content. These alterations were associated with reduced phospholamban phosphorylation, increased CaMKII and ryanodine receptor phosphorylation and activation of pro-apoptotic signalling. Notably, pharmacological inhibition of SIRT1 with EX527 in control cardiomyocytes recapitulated key features of the MetS phenotype, whereas SIRT1 activation with SRT1720 restored mitochondrial membrane potential, reduced reactive oxygen species production, improved Ca²⁺ handling, normalized aberrant phosphorylation of Ca²⁺-handling proteins and attenuated apoptotic signalling. Collectively, these findings identify SIRT1 as a critical integrator of mitochondrial function and Ca²⁺ homeostasis during metabolic stress, highlighting sirtuin-dependent pathways as promising therapeutic targets in metabolic cardiomyopathy.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4646-4658"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Traumatic arteriovenous fistula after ice axe injury 27 years ago: A case report","authors":"Kate N. Thomas,&nbsp;Emma M. W. Jones,&nbsp;Arunesh Majumder,&nbsp;Peter W. Abcarian,&nbsp;Peter J. McLeod","doi":"10.1113/EP093968","DOIUrl":"10.1113/EP093968","url":null,"abstract":"<p>We report a case of a traumatic arteriovenous fistula (AVF) between the superficial femoral artery and femoral vein that went undetected for 27 years following an ice axe injury during a climbing accident in 1997. An AVF is an abnormal connection between an artery and a vein, where blood flows directly from the high-flow arterial system to the low-flow venous system, bypassing the capillaries. A 74-year-old male presented with a 2-year history of extensive left leg swelling. He had visible posterior thigh and calf varicose veins and a small scar to the left medial upper thigh. He was otherwise fit and hiking regularly. He also had mild left ventricular and severe bi-atrial dilation, with high output cardiac failure and cardiac remodelling. With ultrasound, a traumatic AVF between the superficial femoral artery and femoral vein was identified. We also assessed the arterial vasodilatory function in both femoral arteries for a within-subject comparison of the chronic effects of high shear stress – the result of high flows through the AVF. This case study discusses the imaging and physiological test findings, along with further details of the climbing accident which were revealed by the patient. Traumatic AVFs are uncommon, and to our knowledge, this is the first documented case of an AVF resulting from an ice axe injury. Almost three decades later, the moment on the mountain left its mark; this case illustrates the complications associated with an untreated AVF.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":"111 10","pages":"4351-4359"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13405334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An acute crossover trial of passive movement training with and without blood flow restriction to determine the impact on postprandial glycaemia.","authors":"Jay Railton-Sowerby, Ewan Dean, Matthew Davitt, Jack Hayden, Ash Osborne, Donna Shrestha, David Cheneler, Christopher J Gaffney, Paul Hendrickse","doi":"10.1113/EP093866","DOIUrl":"10.1113/EP093866","url":null,"abstract":"<p><p>During glucose uptake into muscle, GLUT-4 can translocate with stimulus from insulin or muscle contraction via exercise, but some exercise-intolerant populations are unable to benefit from improved glycaemic control. We investigated how passive movement training (PMT) and passive movement training with blood flow restriction (PMT+BFR) could be used as an alternative method. The effects on blood lactate and insulin were also investigated. Eleven healthy males (26.9 ± 8.3 years, 25.7 ± 2.1 kg/m²) undertook a crossover trial of three 150-min treatments, control (CTRL), PMT and PMT+BFR, on three separate study visits, separated by ≥24 h. Each participant arrived fasted and consumed a standardised high-carbohydrate meal (522 kcal, 112.5 g carbohydrate). The PMT protocol involved 30 min of intermittent bilateral knee extension/flexion (1 min:1 min work/rest) at an angular velocity of 180°/s through an 80° range of motion. PMT+BFR used a pressure calibrated at 80% arterial occlusion. Blood glucose and lactate were measured every 5 min, with insulin at 0, 30 and 60 min. Acute changes in muscle thickness were recorded using ultrasound pre- and post-intervention. There were no significant differences between the treatment groups for mean glucose (CTRL: 4.59 ± 0.48, PMT: 4.88 ± 0.82, PMT+BFR: 4.51 ± 0.90 mmol/L; P = 0.498). A statistically significant acute difference of muscle thickness (P = 0.00420) from pre- to post-treatment was detected in PMT+BFR. While PMT did not improve postprandial glycaemia with or without BFR, the acute increase in muscle thickness after PMT+BFR suggests that it may be useful in other applications.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4753-4762"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intermittent low-intensity contractions cause a dissociation between maximal motor unit firing rates and changes in torque and contractile speed.","authors":"Alexander M Zero, Raaj A Dudani, Jacob Fanous, Charles L Rice","doi":"10.1113/EP093505","DOIUrl":"10.1113/EP093505","url":null,"abstract":"<p><p>The purpose was to test: (1) whether the decline in maximal motor unit (MU) firing rate is an invariable response when maximal voluntary contraction (MVC) torque is reduced following a submaximal muscle fatiguing task; and (2) whether fatigue-induced slowing of contractile speed and firing rate decline are co-dependent. Ten participants (three females) underwent a protocol (duty cycle, 0.6 s) of knee extensions at 30% MVC for 30 min, which has been shown previously to reduce MVC torque with negligible muscle metabolic disturbances. Electrically evoked quadriceps torque (1, 50 and 100 Hz), MVC torque and maximal firing rates were assessed intermittently throughout the protocol. Intramuscular microelectrodes were inserted into the vastus lateralis and medialis to record MU firing rates (n = 1557). By 30 min, MVC and electrically evoked quadriceps torques declined (30%-50%, all P ≤ 0.02); however, measures of contractile speed increased (∼30%, all P < 0.001). Grouped mean maximal firing rates were not significantly changed (24.1 ± 8.9 Hz) from pre-task (24.7 ± 9.2 Hz, P = 0.16). Therefore, reductions in maximal torque generation, contractile slowing and decreased maximal MU firing rates are not invariable correlates of a fatiguing task. Instead, reduced MVC torque can be dissociated from the usual slowing of maximal firing rates and contractile speed when fatigue is induced with, presumably, negligible metabolic disturbances. The constancy of maximal firing rates despite large reductions in MVC torque supports that firing rate moderation with fatiguing activation is probably attributable to reflexive inhibition from muscle metabolic alterations and thus not directly related to changes in contractile speed.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4722-4737"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13436840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle cramp susceptibility is associated with muscle-specific modulation of human motoneuron discharge patterns.","authors":"Timothée Popesco, Romain Dos Santos, Ilan Cassoli, Gabriel S Trajano, Gregory E P Pearcey, Nicola A Maffiuletti, Chris Donnelly, Bengt Kayser, Nicolas Place","doi":"10.1113/EP093881","DOIUrl":"10.1113/EP093881","url":null,"abstract":"<p><p>Muscle cramps are painful, involuntary contractions thought to arise from altered spinal motoneuron excitability, potentially involving persistent inward currents (PICs). We examined whether cramp susceptibility is associated with altered PIC-related motoneuron behaviour and whether electrically induced cramp modifies these estimates. Twenty-eight healthy, active adults performed triangular plantar-flexor contractions before and after a cramp threshold frequency test designed to evoke cramp in gastrocnemius medialis. Participants were classified as crampers or controls according to cramp test outcome. Contributions of PICs to motoneuron discharge were estimated in soleus and gastrocnemius medialis from high-density surface EMG recordings during triangular contractions decomposed into motor unit spike trains. Discharge rate hysteresis (ΔF), brace height, associated slopes and self-sustained discharge duration characterized PIC-related modulation of motor unit firing. Spinal reflex excitability and centrally mediated neuromuscular responses were assessed using H reflexes and wide-pulse, high-frequency neuromuscular electrical stimulation. At baseline, ΔF in gastrocnemius medialis was lower in crampers than in controls, whereas other PIC-related estimates, wide-pulse, high-frequency-evoked torque, sustained EMG activity, warm-up effect and H-reflex amplitudes did not differ between groups. After the cramp-inducing protocol, ΔF increased in gastrocnemius medialis and self-sustained discharge duration increased in both muscles, while brace height remained unchanged in gastrocnemius medialis but decreased in soleus. Maximal discharge rate in gastrocnemius medialis decreased in crampers but not in controls. These findings indicate that cramp susceptibility is not associated with generalized motoneuronal hyperexcitability, but with subtle, muscle-specific alterations in motoneuron discharge modulation.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4738-4752"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of cannabinoid type 2 receptor agonist (JWH-133) against hepatotoxicity induced by Prangos ferulacea Lindl. extract.","authors":"Mesut Çelik, Aslı Çetin Taşlıdere, Zeynal Mete Karaca, Halil Düzova, İbrahim Halil Geçibesler, Ali Rıza Çalişkan, Çağatay Taşkapan, Kübranur Korkmaz","doi":"10.1113/EP094039","DOIUrl":"10.1113/EP094039","url":null,"abstract":"<p><p>This study investigated Prangos ferulacea (PF)-induced hepatotoxicity, its potential association with endoplasmic reticulum (ER) stress and proinflammatory cytokines, and the effect of the cannabinoid type 2 receptor agonist JWH-133. Rats (n = 37) were divided into four groups: control-sham group (CSG, n = 9), PF extract group (PG, n = 9), PF extract + JWH-133 group (PJG, n = 9) and JWH-133 group (JG, n = 10). Hepatic ER stress markers (CHOP, GRP78 and ATF4), interleukin (IL)-17, IL-23, heat shock protein 72 (HSP72), and calpain, as well as serum IL-17, IL-23, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein and albumin, were assessed. Liver histology was evaluated using haematoxylin-eosin staining, and apoptosis was assessed by caspase-3 immunohistochemistry. No significant between-group differences were observed in hepatic GRP78, CHOP, ATF4, IL-17 or IL-23 levels. Similarly, serum IL-17 and IL-23 levels did not differ significantly among the groups. Calpain levels differed significantly among the groups (P = 0.0017), with higher levels in PG (P = 0.0325) and PJG (P = 0.0076) than in CSG. Compared with CSG, PG and PJG showed lower ALT (P = 0.0021 for both), AST (P = 0.0021 for both), albumin (P = 0.0031 and P = 0.0016, respectively) and total protein (P = 0.0056 and P = 0.0017, respectively) levels. Histopathological damage was significantly greater in PG than in CSG, PJG and JG (all P < 0.0001). Caspase-3 immunoreactivity was intense in PG and limited in PJG. PF extract caused marked liver injury without clear canonical ER stress activation. JWH-133 attenuated histopathological damage, consistent with the potential role of CB2 receptor activation. These findings support ER stress-independent mechanisms and warrant further investigation of CB2 activation as a hepatoprotective strategy.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":"4565-4577"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}