The United States Food and Drug Administration Adverse Event Reporting System (FAERS) logged 27,140 rhabdomyolysis cases from 2004 to 31 March 2020. We used FAERS to identify 14 drugs frequently reported in 6583 rhabdomyolysis cases and to investigate whether mitochondrial toxicity is a common pathway of drug-induced rhabdomyolysis by these drugs. Preliminary screening for mitochondrial toxicity was performed using the acute metabolic switch assay, which is adapted here for use in murine L6 cells. Fenofibrate, risperidone, pregabalin, propofol, and simvastatin lactone drugs were identified as mitotoxic and underwent further investigation, using real-time respirometry (Seahorse Technology) to provide more detail on the mechanism of mitochondrial-induced toxicity. To confirm the human relevance of the findings, fenofibrate and risperidone were evaluated in primary human skeletal muscle-derived cells (HSKMDC), using the acute metabolic switch assay and real-time respirometry, which confirmed this designation, although the toxic effects on the mitochondria were more pronounced in HSKMDC. Overall, these studies demonstrate that the L6 model of acute modification may find utility as an initial, cost-effective screen for identifying potential myotoxicants with relevance to humans and, importantly, that drug-induced mitochondrial dysfunction may be a common mechanism shared by some drugs that induce myotoxicity.

Background: Although semaglutide (Ozempic^®) is being prescribed off-label to individuals with obesity, some concerns have arisen regarding its use, particularly regarding the risk of thyroid and pancreatic disorders. Therefore, it is crucial to screen patients’ medical and family disease histories, as well as certain clinical parameters, before initiating this treatment for obesity or weight management. However, there is limited research investigating whether pretreatment assessment is adopted in clinical practice. Method: This is a single-center retrospective study involving adults who were prescribed semaglutide for obesity or weight management. Demographic data, comorbid conditions, semaglutide-related lab work, and disease history assessments, including pancreatitis, thyroid abnormalities, oculopathy, neuropathy, and any family history of thyroid cancer, were evaluated and documented prior to treatment initiation. Results: In total, 715 patients were included in the study, with an average age of 40.2 ± 12.0 years, and 49.5% of participants were male. The average weight and BMI prior to using semaglutide were 99.8 ± 18.1 kg and 36.3 ± 8.3 kg/m², respectively, with predominantly overweight and obese individuals (collectively 91.3%). Approximately 69% of patients had 3–5 complications, with a high prevalence of cardiovascular and metabolic diseases before using semaglutide. Although HbA1c, serum creatinine, TSH, T3, T4, triglycerides, HDL, LDL, total cholesterol, and total bilirubin were monitored prior to semaglutide use, none of the patients’ pancreatic lipase, amylase, or calcitonin levels were measured. Although it is important to investigate all personal and family disease histories, including thyroid abnormalities, thyroid cancer, pancreatitis, retinopathy, eye problems, and neuropathy prior to semaglutide initiation, checks were only conducted in 1.8% of patients, despite 98.6% having at least one of the diseases assessed pretreatment. Conclusions: The current pretreatment assessment approach for patients prescribed semaglutide for weight reduction is underdeveloped, particularly with regard to assessing the influence of disease history on semaglutide use. This predisposes patients to a risk of severe clinical outcomes, including thyroid cancer, pancreatitis, and retinopathy.

Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has demonstrated substantial efficacy in managing type 2 diabetes mellitus (T2DM). It provides glycemic control, promotes weight loss, and offers cardiovascular protection. Evidence also supports its role in diabetic kidney disease (DKD), a leading global cause of end-stage renal disease. DKD arises from a multifactorial interaction involving hyperglycemia, hypertension, and inflammation, which leads to cumulative nephron loss. Beyond glycemic control, semaglutide’s mechanisms of action target metabolic and hemodynamic pathways that contribute to renal damage. This review evaluates the preclinical and clinical evidence of semaglutide’s role in preventing DKD, focusing on its renal effects and the mechanistic basis for renoprotection. We also position semaglutide within the broader DKD therapeutic landscape by reviewing clinical trial findings, translational studies, real-world evidence, and its effectiveness compared to other drug classes. The expanded actions of semaglutide make it a promising agent in patients with T2DM and DKD and encourage further mechanistic research and long-term evaluation.

Artemisia monosperma is a plant with many traditional uses including some affecting smooth muscles. The A. momosperma essential oil (AMEO) prepared by hydrodistillation from fresh and dry aerial parts was compared qualitatively and quantitatively using GC/MS. The drying process affected the yield and composition of AMEO. The bronchodilator potential was explored using isolated guinea-pig trachea in ex-vivo organ bath setup. In the tracheal contractions induced by different spasmogens, AMEO was able to completely relax contractions induced by carbachol (CCh; 1 µM) and high K+ (80 mM) at closely related doses (p > 0.05) indicating a dual inhibition of phosphodiesterase enzyme (PDE) and voltage-mediated L-type Ca++ channels blocker (CCB) as papaverine. The current study provides scientific support to the medicinal use A. monosperma in respiratory disorders.

Background: Despite the cardiometabolic benefit of semaglutide, its impact on quality of life and whether patients’ characteristics influence clinical outcomes and health-related quality of life (HRQoL) remain ambiguous. Method: A retrospective review of patient charts was conducted after semaglutide initiation to assess the clinical impact of semaglutide, followed by a prospective analysis to evaluate HRQoL using the 36-Item Short Form Health Survey (SF-36). Descriptive and correlative analyses were conducted using SPSS software version 29 (IBM Corp., Armonk, NY, USA). Results: From a total of 715 patients, 255 (average age 59.1 years; 58.1% male participants) were subjected to clinical outcome analysis. The use of semaglutide was associated with significant reductions in HbA1c, total bilirubin, and TG and elevations in T4, TSH, Scr, and HDL. When each fifth value of each clinical parameter was compared with the baseline, gender revealed a significant impact, as females showed increased rates of elevated HDL (73.2% vs. 55.7%), reduced weight (69.8% vs. 55.7%), and reduced BMI (72.5% vs. 53.8%) compared to those in males. Despite the number of comorbidities significantly influencing BMI (p = 0.015), it had no impact on HbA1c post semaglutide use (p = 0.062). The same number of patients (n = 255), albeit having slightly different demographic and clinical characteristics, was included in the HRQoL analysis cohort. Females represented 54.5% of the cohort, and 71.0% were aged between 40 and <65 years. The average scores for all domains within the physical component summary (PCS) and mental component summary (MCS) were below 50, indicating a lack of perceived improvement in the overall quality of participants’ lives considering the pre-treatment period as the basis of comparison. In particular, younger age [OR 0.975, CI95% 0.953–0.998, p = 0.033] and being female [OR 0.273, CI95% 0.162–0.459, p < 0.001] led to reduced odds of scoring ≥ 50 in PCS, indicating a poor physical health state. On the contrary, older age [OR 1.036, CI95% 1.011–1.06, p = 0.004] increased the odds of scoring ≥ 50 in MCS, indicating a better mental health state in elderly vs. young semaglutide users. Although education level had significant influence on PCS, this did not extend to MCS. Upon investigating if type of change in a clinical parameter correlates with PCS and MCS scoring, only the decline in T4 reduced the odds of scoring MCS ≥ 50 [OR 0.5, CI95% 0.274–0.913, p = 0.024], while no significant influence was found either with other parameters or between clinical parameters and PCS. Conclusions: A lack of perceived improvement in HRQoL is noted with semaglutide use. Age, gender, and education play significant roles in HRQoL post semaglutide initiation. Overall, before prescribing semaglutide, patient counseling on its positive and negative effects is crucial to promote long-term adherence and optimize clinical outcomes.

Background/Objectives: The purpose of this research was to investigate the effects of bisphenol A (BPA) exposure on neurobehavioral testing in young Wistar rats and to evaluate the therapeutic potential of Thymus ciliatus (TEO) essential oil to attenuate the damage induced by this chemical toxin. Methods: The essential oil was extracted by hydro-distillation (yield of 2.26%), and the characterization by GC-MS indicates that the major components of Thymus ciliatus oil are thymol (63.33%), p-cymene (13.4%), and σ-terpinene (6.69%). Acute BPA intoxication was induced with a dose of 50 mg/kg orally for 60 days. The neurobehavioral evaluation, performed using a comprehensive set of tests including the forced swim test, dark/light box, Morris water maze, open field test, and sucrose preference test, clearly demonstrated that bisphenol A (BPA) exposure induced significant neurobehavioral impairments. Results: These impairments included reduced exploratory behavior indicative of heightened stress, anxiety, and depressive-like states, as well as deficits in memory and learning. Furthermore, BPA intoxication was associated with metabolic disturbances such as hyperglycemia along with histopathological evidence of brain tissue damage. However, TEO treatment attenuated these adverse effects by restoring neurobehavioral function. Molecular docking analysis revealed an affinity between the major essential oils identified in T. ciliatus, BPA, and the 5HT2C receptor and the MAO, AChE, and BChE enzymes, suggesting a potential mechanism underlying BPA’s effects on behavior and memory. In addition, TEO also showed an interaction with these molecules, suggesting a therapeutic potential against BPA. These findings underscore the promising role of TEO in mitigating the poisonous effects of BPA and pave the way for additional research into the molecular mechanisms and therapeutic uses of natural bioactive compounds for the prevention and treatment of toxic diseases. Thymol, the major compound in TEO, exhibited activity related to the dopamine and serotonin pathways, so it could have potential antidepressant properties. Conclusions: Thymol might be a promising candidate for the treatment of neurodegenerative and neurological disorders such as depression, Parkinson’s disease, and Alzheimer’s disease while also preventing histological damage in the brain.