Rhabdomyolysis Research Articles

Creatinine levels in French children with Down syndrome up to ten years old.

Assess creatinine levels in French children with Down syndrome (DS) on the basis of the relationship between creatinine levels and age. The study included 279 children with DS aged 0 to 10years who had been regularly monitored between 2004 and 2021 in a single genetics department and who had had at least one creatinine measurement. The creatinine level curves were established by estimating the median and the quantiles of order 2.5 and 97.5% according to age. A Generalized Additive Model for Location, Scale, and Shape was used. The results showed higher creatinine levels in children with DS than in children from the general population. Conclusion: The present results allow to propose an original chart of creatinine levels according to age in French children with DS, which should help optimize their medical management and improve the early detection of renal diseases. What is Known: • Creatinine is a product of muscle breakdown and depends on muscle massand children with Down syndrome have muscle and growth characteristics that differ from those of the general paediatric population. • Serum creatinine values in Japanese children with DS are higher than those of children from the general Japanese population. What is New: • Creatinine values in French children with DS are higher than those of children from the general French population. • The proposed original chart for creatinine values according to age, specifically designed for individuals up to 10years old, should serve for further investigation, prevention, and follow-up of children with DS.

Reducing dietary crude protein: Effects on digestibility, nitrogen balance, and blood metabolites in late-lactation Holstein cows

Our objectives were to determine the effects of reducing dietary crude protein (CP) concentration on nutrient digestibility, rumen function, N balance, and serum AA concentration for dairy cows in late lactation. At the initiation of the experimental period, we stratified Holstein cows (n = 128; mean ± standard deviation 224 ± 54 d in milk) by parity and days pregnant (86 ± 25 d) and assigned them to 1 of 16 pens. For 3 wk, all cows received a covariate diet containing 16.9% CP [dry matter (DM) basis]. For the subsequent 12 wk, we assigned pens to 1 of 4 treatments containing 16.2, 14.4, 13.4, or 11.9% CP (DM basis) in a randomized complete block design. Diets were fed as a total mixed ration once daily. To reduce dietary CP, we replaced soybean meal with soybean hulls in the concentrate mix (DM basis). Diet evaluations suggested that several EAA, especially His, limited productivity as dietary CP declined. Digestibility of DM and CP decreased linearly with dietary CP reduction. Digestibility of neutral detergent fiber and potentially digestible neutral detergent fiber tended to respond in a quadratic pattern with the greatest digestibility at intermediate treatments. The reduction in dietary CP did not affect ruminal pH, but ruminal ammonia-N and branched-chain VFA concentrations declined linearly. The concentration of milk urea-N and plasma urea-N, secretion of milk N, and excretions of fecal N, urinary N, urinary urea-N, and unaccounted N decreased linearly with the reduction in dietary CP concentration. Urinary N expressed as a percentage of N intake was unaffected by dietary CP. Serum concentrations of total essential AA and non-essential AA were unaffected by dietary CP concentration. However, the ratio of essential to non-essential AA decreased with decreasing dietary CP. Serum 3-methylhistidine concentration increased linearly with decreasing dietary CP concentration, indicating greater skeletal muscle breakdown. Although our trial confirmed that reducing dietary CP decreased absolute excretion of urinary N, diet evaluations suggested that milk protein production decreased as certain essential AA became increasingly limited. Thus, reduced-CP diets have the potential to lessen reactive-N outputs of late lactation cows, but more research is needed to design diets that minimize deleterious effects on productivity.

Recent Advances and Updates in Rhabdomyolysis: A Comprehensive Review

Rhabdomyolysis (RML) is a complex clinical syndrome marked by the breakdown of skeletal muscle cells, with historical recognition dating back to biblical times and modern understanding evolving since World War II. This comprehensive review explores the diverse landscape of RML, encompassing its epidemiology, etiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis. As a result of trauma or non-traumatic muscle injuries, pathogenesis involves the release of intracellular components into the bloodstream. Epidemiologically, RML exhibits demographic nuances, emphasizing the importance of recognizing risk factors for prevention. Clinical manifestations range from the classic triad of muscle pain, weakness, and dark urine to diverse presentations. Diagnosis involves evaluating elevated creatine kinase levels and myoglobinuria, with management strategies focusing on fluid balance, AKI prevention, and addressing underlying causes. The prognosis is diverse, influenced by complications such as AKI, with various scoring systems aiding risk assessment. Prevention and treatment strategies include a multifaceted approach, integrating tailored warm-ups, mindful exercise, education, and dietary modifications. Overall, the prognosis for RML remains favorable, underscoring the significance of meticulous management. This review provides a comprehensive understanding of RML, bridging historical insights with contemporary medical strategies and guiding ongoing research and advancements in patient care for this intricate condition. RML serves as a paradigm for integrating nuanced historical perspectives and modern medical approaches, highlighting the intricate balance required for effective management in clinical practice.

Recent Advances and Updates in Rhabdomyolysis: A Comprehensive Review

Rhabdomyolysis (RML) is a complex clinical syndrome marked by the breakdown of skeletal muscle cells, with historical recognition dating back to biblical times and modern understanding evolving since World War II. This comprehensive review explores the diverse landscape of RML, encompassing its epidemiology, etiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis. As a result of trauma or non-traumatic muscle injuries, pathogenesis involves the release of intracellular components into the bloodstream. Epidemiologically, RML exhibits demographic nuances, emphasizing the importance of recognizing risk factors for prevention. Clinical manifestations range from the classic triad of muscle pain, weakness, and dark urine to diverse presentations. Diagnosis involves evaluating elevated creatine kinase levels and myoglobinuria, with management strategies focusing on fluid balance, AKI prevention, and addressing underlying causes. The prognosis is diverse, influenced by complications such as AKI, with various scoring systems aiding risk assessment. Prevention and treatment strategies include a multifaceted approach, integrating tailored warm-ups, mindful exercise, education, and dietary modifications. Overall, the prognosis for RML remains favorable, underscoring the significance of meticulous management. This review provides a comprehensive understanding of RML, bridging historical insights with contemporary medical strategies and guiding ongoing research and advancements in patient care for this intricate condition. RML serves as a paradigm for integrating nuanced historical perspectives and modern medical approaches, highlighting the intricate balance required for effective management in clinical practice

Serum procalcitonin levels are associated with rhabdomyolysis following exertional heatstroke: an over 10-year intensive care survey.

Heatstroke has become a common emergency event in hospitals. Procalcitonin (PCT) is used as a biomarker of infection in the emergency department (ED), but its role in rhabdomyolysis (RM) following exertional heatstroke (EHS) remains unclear. A retrospective cohort study enrolled patients with EHS from the intensive care unit (ICU). We collected RM biomarkers, inflammation markers, critical disease scores at admission, 24 h, 48 h, and discharge, and 90-day mortality. Correlation analysis, linear regression and curve fitting were used to identify the relationship between PCT and RM. A total of 162 patients were recruited and divided into RM (n=56) and non-RM (n=106) groups. PCT was positively correlated with myoglobin (Mb), acute hepatic injury, disseminated intravascular coagulation (DIC), Sequential Organ Failure Assessment (SOFA) score, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score, with correlation coefficients of 0.214, 0.237, 0.285, 0.454, and 0.368, respectively (all P<0.05). Interestingly, the results of curve fitting revealed a nonlinear relationship between PCT and RM, and a two-piecewise linear regression model showed that PCT was related to RM with an odds ratio of 1.3 and a cut-off of <4.6 ng/mL. Survival analysis revealed that RM was associated with higher mortality compared to non-RM cases (P=0.0093). High serum PCT concentrations are associated with RM after EHS in critically ill patients. Elevated PCT concentrations should be interpreted cautiously in patients with EHS in the ED.

Time-to-onset Analysis of Rhabdomyolysis due to Different Proton Pump Inhibitors Using a Pharmacovigilance Database.

Recent research has increasingly demonstrated an association between proton pump inhibitors (PPIs) and serious adverse events. This study aimed to evaluate the association between PPI and rhabdomyolysis (RM), examining its time-to-onset profiles using the Japanese Adverse Drug Event Report (JADER) database. Data spanning from April 2004 to March 2022 were used. The association between PPIs and RM was evaluated using the reporting odds ratio (ROR), adjusted for sex and age. Subsequent analyses were conducted after excluding cases involving concomitant use of statins or fibrates. Furthermore, the onset time of RM and Weibull distribution parameters were calculated to evaluate the expression profile of RM, and the outcomes were examined. RM was associated with the use of esomeprazole, omeprazole, and rabeprazole, even in the absence of concomitant statin or fibrate use. The median time to RM onset varied among PPIs, ranging from 6.5 to 127 d. The Weibull distribution parameters indicated that the hazard types of nearly all orally administered PPIs were classified as early failure or close to random failure. Regarding outcomes, cases of death were reported for all PPIs except vonoprazan. The findings suggest the need for vigilant monitoring of RM during PPI administration, particularly in the early stages, considering the varying onset times.

Acute kidney injury due to rhabdomyolysis in a patient with primary hypothyroidism

ABSTRACT Acute kidney injury (AKI), secondary to rhabdomyolysis (RM) following strenuous work with primary hypothyroidism, is rare. Here, is a case report of a 32-year-old female who developed AKI following strenuous work in a paddy field in the background of overt primary hypothyroidism. High serum creatine phosphokinase levels and high concentration of myoglobin in urine were noted, which was suggestive of myoglobinuria due to severe RM and elevated creatine level in serum, which indicated AKI. The patient’s condition improved significantly after initiation of levothyroxine replacement therapy and hemodialysis. AKI secondary to RM with primary hypothyroidism and strenuous work as a precipitating factor is quite rare. We expect this case report to add to the existing literature on this subject.

Targeted treatment of rat AKI induced by rhabdomyolysis using BMSC derived magnetic exosomes and its mechanism.

Introduction: rhabdomyolysis (RM) is a serious syndrome. A large area of muscle injury and dissolution induces acute kidney injury (AKI), which results in a high incidence and mortality rate. Exosomes released by mesenchymal stem cells (MSCs) have been used to treat AKI induced by rhabdomyolysis and have shown regenerative effects. However, the most serious drawbacks of these methods are poor targeting and a low enrichment rate after systemic administration. Methods: in this study, we demonstrated that magnetic exosomes derived from bone marrow mesenchymal stem cells (BMSCs) can directly target damaged muscles rather than kidneys using an external magnetic field. Results: magnetic navigation exosomes reduced the dissolution of damaged muscles, greatly reduced the release of cellular contents, slowed the development of AKI. Discussion: in summary, our proposed method can overcome the shortcomings of poor targeting in traditional exosome therapy. Moreover, in the rhabdomyolysis-induced AKI model, we propose for the first time an exosome therapy mode that directly targets damaged muscles through magnetic navigation.

Predictive value of serum myoglobin and lactate dehydrogenase in rhabdomyolysis-induced acute kidney injury from severe heatstroke.

To explore the predictive utility of serum myoglobin (Mb) and lactate dehydrogenase (LDH) for acute kidney injury (AKI) secondary to rhabdomyolysis (RM) in severe heatstroke patients. A retrospective analysis of 58 RM patients with severe heatstroke at Shanghai Ninth People's Hospital from June 2019 to May 2022 was conducted. Patients were categorized into AKI and non-AKI groups. Laboratory indices were compared, and receiver operating characteristic (ROC) curves were used to assess the predictive value of serum biomarkers for AKI. Creatine kinase, Mb, LDH, creatinine, and blood urea nitrogen levels were significantly higher in the AKI group (P<0.05). Serum Mb and LDH were positively correlated with serum creatinine (r=0.6772 and r=0.6816, respectively; P<0.05). The area under the ROC curve (AUC) for serum Mb was 0.6692 (95% CI: 0.5253-0.8131) with a cut-off of 1024 ng/ml, while for LDH it was 0.8277 (95% CI: 0.7182-0.9371) with a cut-off of 1342 U/L. Combining serum Mb and LDH improved the AUC to 0.9116 (95% CI: 0.8219-1.001). Serum Mb and LDH levels are elevated in RM-induced AKI following severe heatstroke, and their combination offers substantial predictive value for AKI in these patients.

Trans-sodium crocetinate suppresses apoptotic and oxidative response following myoglobin-induced cytotoxicity in HEK-293 cells.

Rhabdomyolysis (RM) is a serious fatal syndrome. The RM leads to acute kidney injury (AKI) as a fatal complication. The belief is that RM-induced AKI is triggered by myoglobin (MB). MB activates oxidative and apoptotic pathways. Trans-sodium crocetinate (TSC) is obtained from saffron. It has anti-oxidant and renoprotective effects. This research was designed to assess the mechanisms of MB-induced cytotoxicity in HEK-293 cells (human embryonic kidney cells) as well as the possible effects of TSC against MB-induced cytotoxicity. HEK-293 cells were exposed to diverse concentrations of TSC (2.5, 5, 10, 20, 40, 80, and 100 µM) for 24 hr. Then, MB (9 mg/ml) was added to the cells. After 24 hr, cell viability was measured through MTT, and the values of ROS generation were calculated using DCFH-DA assay. Also, autophagy and apoptosis markers in cells were assessed by western blot analysis. MB decreased viability and increased ROS levels in HEK-293 cells. However, pretreatment of HEK-293 cells with TSC for 24 hr reduced the cytotoxicity and ROS production caused by MB. Furthermore, MB enhanced both the apoptosis (cleaved caspase-3 and Bax/Bcl-2 ratio) and autophagy markers (LC3II/I ratio and Beclin-1) in HEK-293 cells. On the other hand, TSC pretreatment condensed the levels of autophagy and apoptosis criteria in response to MB cytotoxicity. TSC has a positive effect in preventing MB-induced cytotoxicity in HEK-293 cells by increasing anti-oxidant activity and regulation of apoptotic and autophagy signaling pathways.

Acute Kidney Injury Due to Rhabdomyolysis: A Review of Pathophysiology, Causes, and Cases Reported in the Literature, 2011–2021

Introduction: Rhabdomyolysis (RML) is characterized by the destruction of muscle fibers and the release of intracellular constituents, with the potential to cause local and systemic complications, such as acute kidney injury (AKI). Methodology: Literature review in which articles were analyzed between 2011 and 2021, from the PubMed database. Results: RML can occur directly, indirectly, or secondary to trauma, metabolic disorders, medications and exogenous intoxication. Clinically, it may present asymptomatically, but a classic triad consisting of myalgia, generalized weakness and dark urine is common. AKI, despite being a late complication, is common. Laboratory markers used to diagnose RML are serum Creatine Kinase (CK) and serum and urinary Myoglobin, with CK being more sensitive. The approach can occur through classic strategies, such as hydration, diuretics, alkalinization and renal replacement therapy (RRT), but also through new strategies, such as iron chelators and antioxidants; anti-inflammatories and new extracorporeal blood filter. Discussion: Trauma was the most common etiology of AKI due to RML, with a minority of patients requiring RRT. Furthermore, it was found that COVID-19 infection did not result in major kidney complications. Strenuous exercise has been shown to be a rare etiology of AKI due to RML. Other less common causes were drug use/intoxication and metabolic diseases, the majority of which patients did not require RRT or had a favorable outcome. Conclusion: RML is a potentially serious condition, making it important to know its causes and management in order to reduce the chances of serious complications and to avoid patient death.

Metabolomics analysis to interpret changes in physiological and metabolic responses to chronic heat stress in Pekin ducks

Heat stress (HS) is a major environmental threat that affects duck production in subtropical and tropical regions, especially in summer. This study aimed to evaluate the physiological and metabolic responses of Pekin ducks to chronic HS conditions via liquid chromatography-mass spectrometry (LC-MS) using a paired-fed (PF) experimental design. On the basis of equivalent feed intake (HS vs. PF), HS significantly reduced growth performance and the percentage of leg and breast muscles, however, markedly increased the percentage of abdominal fat and breast skin fat. Serum metabolomics results revealed that heat-stressed ducks showed enhanced glycolysis and pentose phosphate pathways, as demonstrated by higher glucose 6-phosphate and 6-phogluconic acid levels in the PF vs. HS comparison. HS decreased hepatic mRNA levels of mitochondrial fatty acid β-oxidation-related genes (MCAD and SCAD) compared to the PF group, resulting in acetylcarnitine accumulation in serum. Moreover, HS elevated the concentrations of serum amino acids and mRNA levels of ubiquitination-related genes (MuRF1 and MAFbx) in the skeletal muscle and amino acid transporter-related genes (SLC1A1 and SLC7A1) and gluconeogenesis-related genes (PCK1 and PCase) in the liver compared to the PF group. When compared to the normal control group (NC), HS further decreased growth performance, but it elevated the abdominal fat rate. However, increased mRNA levels of ubiquitination-related genes and serum amino acid accumulation were not observed in the HS group compared to the NC group, implying that reduced feed intake masked the effect of HS on skeletal muscle breakdown and is a form of protection for the organism. These results suggest that chronic HS induces protein degradation in the skeletal muscle to provide amino acids for hepatic gluconeogenesis to provide sufficient energy, as Pekin ducks under HS conditions failed to efficiently oxidise fatty acids and ketones in the mitochondria, leading to poor growth performance and slaughter characteristics.

Assessment of rhabdomyolysis-induced acute kidney injury with chemical exchange saturation transfer magnetic resonance imaging.

Rhabdomyolysis (RM)-induced acute kidney injury (AKI) is a common renal disease with low survival rate and inadequate prognosis. In this study, we investigate the feasibility of chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) for assessing the progression of RM-induced AKI in a mouse model. AKI was induced in C57BL/6J mice via intramuscular injection of 7.5 mL/kg glycerol (n=30). Subsequently, serum creatinine (SCr), blood urea nitrogen (BUN), and hematoxylin-eosin (HE) and Masson staining, were performed. Longitudinal CEST-MRI was conducted on days 1, 3, 7, 15, and 30 after AKI induction using a 7.0-T MRI system. CEST-MRI quantification parameters including magnetization transfer ratio (MTR), MTR asymmetric analysis (MTRasym), apparent amide proton transfer (APT*), and apparent relayed nuclear Overhauser effect (rNOE*) were used to investigate the feasibility of detecting RM-induced renal damage. Significant increases of SCr and BUN demonstrated established AKI. The HE staining revealed various degrees of tubular damage, and Masson staining indicted an increase in the degree of fibrosis in the injured kidneys. Among CEST parameters, the cortical MTR presented a significant difference, and it also showed the best diagnostic performance for AKI [area under the receiver operating characteristic curve (AUC) =0.915] and moderate negative correlations with SCr and BUN. On the first day of renal damage, MTR was significantly reduced in cortex (22.7%±0.04%, P=0.013), outer stripe of outer medulla (24.7%±1.6%, P<0.001), and inner stripe of outer medulla (27.0%±1.5%, P<0.001) compared to the control group. Longitudinally, MTR increased steadily with AKI progression. The MTR obtained from CEST-MRI is sensitive to the pathological changes in RM-induced AKI, indicating its potential clinical utility for the assessment of kidney diseases.

NEW PREDICTIVE BIOMARKERS FOR SCREENING COVID-19 PATIENTS WITH RHABDOMYOLYSIS IN COMBINATION WITH CYSTATIN C.

Purpose: Cystatin C (CysC) has been linked to the prognosis of corona virus disease 2019 (COVID-19). The study aims to investigate a predictor correlated with CysC screening for poor prognosis in COVID-19 patients combined with skeletal muscle (SKM) impairment and rhabdomyolysis (RM). Methods: A single-center retrospective cohort analysis was carried out. Demographic information, clinical data, laboratory test results, and clinical outcome data were gathered and analyzed. Results: According to the inclusion and exclusion criteria, 382 patients were included in this study. The subjects were divided into three groups based on CysC tertiles. Multivariate analysis revealed that SaO 2 (hazard ratio [HR], 0.946; 95% confidence interval [CI], 0.906-0.987; P = 0.011), CysC (HR, 2.124; 95% CI, 1.223-3.689; P = 0.008), aspartate aminotransferase (AST) (HR, 1.009; 95% CI, 1.000-1.018; P = 0.041), and hypersensitive C-reactive protein (HR, 1.005; 95% CI, 1.000-1.010; P = 0.045) were significantly associated with survivals. The area under curve (AUC) in the model characterized by RM incidence was 0.819 (0.698-0.941), as shown by CysC receiver operating characteristic curves. LDH*CysC and AST*CysC had better predictive values than CysC and the best prediction for RM, with an AUC of 0.880 (0.796,0.964) for LDH*CysC ( P < 0.05, vs CysC) and 0.925 (0.878,0.972) for AST*CysC ( P < 0.05, vs CysC). Conclusion: CysC is an essential evaluation indicator for COVID-19 patients' prognosis. AST*CysC and LDH*CysC have superior predictive value to CysC for SKM, RM, and death, and optimal classification for RM.

Вплив водорозчинних С60-фулеренів на перебіг cпричиненого рабдоміолізом пошкодження нирок різного ступеня тяжкості

Rhabdomyolysis, as an acute stage of myopathy, causes kidney damage. Literary data indicate that this pathology is caused by the accumulation of muscle breakdown products and is associated with oxidative stress. Therefore, the effect of water-soluble C60 fullerenes (C60), as powerful antioxidants, at different doses of intraperitoneal administration (1 and 2 mg·kg-1) on the development of kidney damage due to the rhabdomyolysis of various severity degrees, which was caused by the intramuscular injection of a 50% glycerol solution into the muscle soleus in doses of 5, 10 and 15 mg·kg-1 was evaluated in the present work. C60 injections at doses of 2 mg·kg-1 have been shown to most effectively increase glomerular filtration rate (GFR) in severe renal failure (by 29, 38 and 51% on the 3rd, 6th and 9th day of the experiment, respectively). Changes in the content of creatine phosphokinase and activity of glutathione peroxidase in the blood of experimental animals are correlated well (r &gt; 0.94) with changes in GFR with the use of C60. This opens up new opportunities in the therapy of pathological conditions of the muscular system, which are caused by rhabdomyolysis, release of labile Fe3+ from damaged muscle fibers and associated oxidative stress.

Myostatin as a Prognostic Biomarker in Hepatic Cirrhosis Patients with Sarcopenia

Cirrhosis represents the advanced stage of numerous chronic liver conditions. Sarcopenia is a frequently overlooked complication in cirrhotic patients, resulting from factors such as insufficient protein intake, malabsorption, diminished muscle growth, and increased muscle breakdown. Sarcopenia is a multifaceted, chronic condition associated with elevated risks of morbidity and mortality. In the field of hepatology, sarcopenia is typically described as a phenotypic indication of muscle mass loss, affecting approximately 30-70% of liver cirrhosis patients. Sarcopenia has been scientifically linked to an increased risk of falls, reduced quality of life, the emergence of acute decompensated liver failure, and mortality in cirrhotic patients. Myostatin, classified as a cytokine within the transforming growth factor beta (TGF-β) family, is recognized for its role in disrupting protein synthesis. It functions as a negative regulator of muscle growth, inhibiting myogenesisand is linked to the onset of sarcopenia. Extensive literature supports the prognostic importance of sarcopenia in cirrhosis, and serum myostatin levels have the potential to serve as a valuable biomarker. Elevated myostatin concentrations have been linked to the presence of sarcopenia and decreased survival rates in individuals diagnosed with liver cirrhosis.

C(60) fullerene attenuates the signs of acute renal failure in rats under rhabdomyolysis due to inhibition of oxidative stress

Rhabdomyolysis, as an acute stage of myopathy is known to be associated with the accumulation of muscle breakdown products, acute renal failure and oxidative stress. The goal of the study was to evaluate the effect of C60 fullerene as an antioxidant on kidney damage in the model of glycerol-induced rhabdomyolysis in rats. The study was conducted on male Wistar rats, divided into the following experimental groups: control animals, animals intramuscularly injected with glycerol in a doses of 5, 10 and 15 mg/kg and those intraperitoneally injected daily with C60 fullerene aqueous solution (C60FAS) in a dose of 1 or 2 mg/kg at 48 h after glycerol administration­. Monitoring of the biochemical and morphological indicators was carried out on 3rd, 6th and 9th days of the experiment. A close correlation between the acute renal damage severity, increased creatinine and urea level, superoxide dismutase (SOD) and catalase (CAT) activity in the blood of rats was observed. It was shown that in rats which received 2 mg/kg of C60FAS the renal glomeruli size and necrosis manifestations were attenuated, whereas SOD and CAT activity in the blood was significantly decreased. The results obtained may be useful for developing approaches to the treatment of pathological conditions of the muscular system caused by rhabdomyolysis and associated oxidative stress. Keywords: acute renal failure, biochemical parameters, C60 fullerene, histopathology, muscle soleus, rhabdomyolysis

Penehyclidine Hydrochloride Improves Rhabdomyolysis-Mediated Acute Kidney Injury by Inhibiting Ferroptosis through the HIF-1α/MT1G Axis

Background: Penehyclidine hydrochloride (PHC) has been shown to be effective in the treatment of rhabdomyolysis (RM)-induced acute kidney injury (AKI). Our research sought to investigate the pharmacological effects and mechanisms of PHC on RM-induced AKI. Methods: RM-induced AKI models were established by FeG treatment and glycerol injection. Cell viability was analyzed by cell counting kit-8 assay. Reactive oxygen species (ROS) levels were examined by flow cytometry. The LDH, Fe2+, MPO, MDA, and GSH levels were measured using the corresponding kits. The interaction between HIF-1α and MT1G was analyzed by dual-luciferase reporter gene and chromatin immunoprecipitation assays. The kidney pathological alterations were examined by hematoxylin-eosin staining. The levels of serum creatinine, uric acid, and blood urea nitrogen were examined using ELISA. Ferroptosis-related proteins (SLC7A11, GPX4, and ACSL4) were analyzed by Western blot. Results: PHC administration increased FeG-treated HK-2 cell viability, reduced ROS, LDH, Fe2+, MPO, MDA, and ACSL4 levels, and raised GSH, SLC7A11, and GPX4 levels in cells, suggesting that PHC improved FeG-induced HK-2 cell ferroptosis and injury. PHC protected against AKI primarily by suppressing ferroptosis. HIF-1α blocked the SLC7A11/GPX4 pathway by transcriptionally activating MT1G. PHC alleviated glycerol-induced kidney injury in rats by inhibiting ferroptosis. Conclusion: PHC improved RM-mediated AKI by inhibiting ferroptosis through the HIF-1α/MT1G/SLC7A11/GPX4 axis.

The animal protein hydrolysate attenuates sarcopenia via the muscle-gut axis in aged mice

Age-related muscle loss and dysfunction, sarcopenia, is a common condition that results in poor quality of life in the elderly. Protein supplementation is a potential strategy for preventing sarcopenia and increasing muscle synthesis, but the effectiveness of protein type and level in improving sarcopenia is not well understood. In this study, we compared animal protein hydrolysate (APH), which has a high protein digestibility-corrected amino acid score (PDCAAS) and low molecular weight, with casein as a control group to investigate the effects and mechanisms of sarcopenia improvement, with a particular focus on the gut-muscle axis. APH supplementation improved age-related declines in muscle mass, grip strength, hind leg thickness, muscle protein level, muscle fiber size, and myokine levels, compared to the control group. In particular, levels of plasma cortisol, muscle lipids, and muscle collagen were markedly reduced by APH supplements in the aged mice. Furthermore, APH efficiently recovered the concentration of total SCFAs including acetic, propionic, and isovaleric acids decreased in aged mice. Finally, APH induced changes in gut microbiota and increased production of SCFAs, which were positively correlated with muscle protein level and negatively correlated with pro-inflammatory cytokines. In conclusion, APH can help to inhibit age-related sarcopenia by increasing muscle synthesis, inhibiting muscle breakdown, and potentially modulating the gut-muscle axis.

Clinical and Epidemiological Characteristics of Rhabdomyolysis: A Retrospective Study.

Rhabdomyolysis (RM) refers to a clinical syndrome in which muscle cells are damaged by various causes and the clinical manifestations are mainly muscle pain, weakness, and dark urine. Acute kidney injury (AKI) is a serious complication of RM with complex mechanisms and high mortality. Therefore, understanding the pathogenesis and clinical manifestations, early diagnosis and treatment of RM are crucial to improve its prognosis. Analysis of medical records of RM patients admitted to Tianjin Medical University General Hospital from October 2019 to October 2022. Statistical software SPSS 25.0 was used to analyze the data. The risk factors of RM-complicated AKI were analyzed by logistic regression. The receiver operating characteristic (ROC) curve was plotted, the area under the curve (AUC) was calculated, and the optimal cutoff value was determined by the Youden index. P < 0.05 indicates a statistically significant difference between the groups. Among the 71 patients, the median age of the patients was 53.0 (30.0, 71.0) years and was 2.5 times higher in men than in women. Infection was the most common etiology. History of alcohol consumption, CK, and creatinine were independent influencing factors for AKI due to RM. Logistic regression analysis showed that CK combined with creatinine had a better predictive value than the single index. Our study revealed the clinical and laboratory characteristics of RM in the population attending the Tianjin Medical University General Hospital in the last three years, which is a reference for future multicenter, prospective studies.