Sexual dimorphism in acute myocardial infarction-induced acute kidney injury: cardiorenal deteriorating effects of ovariectomy in premenopausal female mice.

Acute kidney injury (AKI) is a common complication of cardiovascular diseases (CVDs) in both males and females, increasing mortality rate substantially. Premenopausal females appear to be more protected, suggesting a potential protective role of female sex hormones. Here, we tested the hypothesis that ovariectomy (OVX) eliminates the beneficial effect of female sex on renal protection following acute myocardial infarction (MI). Seven days post-MI, both sexes exhibited worsened kidney function and a substantial decrease in total kidney NAD levels. Unlike MI female mice, MI males showed exacerbated morphological alterations with increased proinflammatory, proapoptotic, and profibrotic biomarkers. The expression of NAD+ biosynthetic enzymes NAMPT and NMRK-1 was increased in MI females only, while males showed a substantial increase in NAD+ consuming enzyme PARP-1. OVX did not eliminate the female-sex protection of glomerular morphology but was associated with swelling of proximal convoluted tubules with MI as in males. With OVX, MI females had enhanced proinflammatory cytokine release, and a further decrease in creatinine clearance and urine output was observed. Our findings suggest that MI induced AKI in both sexes with pre-menopausal female mice being more protected. Ovariectomy worsens aspects of AKI in females after MI, which may portend increased risk for development of chronic kidney disease.

Cooling Down Inflammation in the Cardiovascular System via the Nicotinic Acetylcholine Receptor.

ABSTRACT: Inflammation is a major player in many cardiovascular diseases including hypertension, atherosclerosis, myocardial infarction, and heart failure. In many individuals, these conditions coexist and mutually exacerbate each other's progression. The pathophysiology of these diseases entails the active involvement of both innate and adaptive immune cells. Immune cells that possess the α7 subunit of the nicotinic acetylcholine receptor on their surface have the potential to be targeted through both pharmacological and electrical stimulation of the cholinergic system. The cholinergic system regulates the inflammatory response to various stressors in different organ systems by systematically suppressing spleen-derived monocytes and chemokines and locally improving immune cell function. Research on the cardiovascular system has demonstrated the potential for atheroma plaque stabilization and regression as favorable outcomes. Smaller infarct size and reduced fibrosis have been associated with improved cardiac function and a decrease in adverse cardiac remodeling. Furthermore, enhanced electrical stability of the myocardium can lead to a reduction in the incidence of ventricular tachyarrhythmia. In addition, improving mitochondrial dysfunction and decreasing oxidative stress can result in less myocardial tissue damage caused by reperfusion injury. Restoring baroreflex activity and reduction in renal damage can promote blood pressure regulation and help counteract hypertension. Thus, the present review highlights the potential of nicotinic acetylcholine receptor activation as a natural approach to alleviate the adverse consequences of inflammation in the cardiovascular system.

Tobacco cigarette smoking exacerbates aortic calcification in an early stage of myocardial infarction in a female mouse model.

Despite increased social awareness, marketing restraints, tobacco taxation, and available smoking cessation rehab programs, active and passive smoking remain a worldwide challenging epidemic and a key risk factor for cardiovascular diseases development. Although cardiovascular (CV) protection is more pronounced in women than in men due to estrogenic effects, tobacco cigarette smoking exposure seems to alter this protection by modulating estrogen actions via undefined mechanisms. Premenopausal cigarette smoking women are at higher risk of adverse CV effects than non-smokers. In this study, we investigated the impact of cigarette smoking on early CV injury after myocardial infarction (MI) in non-menopausal female mice. Aortic arch calcification, fibrosis, reactive oxygen species, and gene expression of inflammatory and calcification genes were exaggerated in mice exposed to cigarette smoke (CS). These findings suggest that aortic injury following MI, characterized by vascular smooth muscle cells transdifferentiation, calcification, inflammation, and collagen deposition but not cardiac dysfunction is exacerbated with CS exposure. The novel findings of this study highlight the importance of aortic injury on short and long-term prognosis in CS-exposed MI females. Linking those findings to estrogen alteration is probable and entails investigation.

Worsening baroreflex sensitivity on progression to type 2 diabetes: localized vs. systemic inflammation and role of antidiabetic therapy.

Cardiac autonomic neuropathy (CAN) is an early cardiovascular manifestation of type 2 diabetes (T2D) that constitutes an independent risk factor for cardiovascular mortality and morbidity. Nevertheless, its underlying pathophysiology remains poorly understood. We recently showed that localized perivascular adipose tissue (PVAT) inflammation underlies the incidence of parasympathetic CAN in prediabetes. Here, we extend our investigation to provide a mechanistic framework for the evolution of autonomic impairment as the metabolic insult worsens. Early metabolic dysfunction was induced in rats fed a mild hypercaloric diet. Two low-dose streptozotocin injections were used to evoke a state of late decompensated T2D. Cardiac autonomic function was assessed by invasive measurement of baroreflex sensitivity using the vasoactive method. Progression into T2D was associated with aggravation of CAN to include both sympathetic and parasympathetic arms. Unlike prediabetic rats, T2D rats showed markers of brainstem neuronal injury and inflammation as well as increased serum levels of IL-1ß. Experiments on PC12 cells differentiated into sympathetic-like neurons demonstrated that brainstem injury observed in T2D rats resulted from exposure to possible proinflammatory mediators in rat serum rather than a direct effect of the altered metabolic profile. CAN and the associated cardiovascular damage in T2D only responded to combined treatment with insulin to manage hyperglycemia in addition to a nonhypoglycemic dose of metformin or pioglitazone providing an anti-inflammatory effect, coincident with the effect of these combinations on serum IL-1ß. Our present results indicate that CAN worsening upon progression to T2D involves brainstem inflammatory changes likely triggered by systemic inflammation.

IL-33 induces type-2-cytokine phenotype but exacerbates cardiac remodeling post-myocardial infarction with eosinophil recruitment, worsened systolic dysfunction, and ventricular wall rupture.

Myocardial infarction (MI) is the leading cause of mortality worldwide. Interleukin (IL)-33 (IL-33) is a cytokine present in most cardiac cells and is secreted on necrosis where it acts as a functional ligand for the ST2 receptor. Although IL-33/ST2 axis is protective against various forms of cardiovascular diseases, some studies suggest potential detrimental roles for IL-33 signaling. The aim of the present study was to examine the effect of IL-33 administration on cardiac function post-MI in mice. MI was induced by coronary artery ligation. Mice were treated with IL-33 (1 µg/day) or vehicle for 4 and 7 days. Functional and molecular changes of the left ventricle (LV) were assessed. Single cell suspensions were obtained from bone marrow, heart, spleen, and peripheral blood to assess the immune cells using flow cytometry at 1, 3, and 7 days post-MI in IL-33 or vehicle-treated animals. The results of the present study suggest that IL-33 is effective in activating a type 2 cytokine milieu in the damaged heart, consistent with reduced early inflammatory and pro-fibrotic response. However, IL-33 administration was associated with worsened cardiac function and adverse cardiac remodeling in the MI mouse model. IL-33 administration increased infarct size, LV hypertrophy, cardiomyocyte death, and overall mortality rate due to cardiac rupture. Moreover, IL-33-treated MI mice displayed a significant myocardial eosinophil infiltration at 7 days post-MI when compared with vehicle-treated MI mice. The present study reveals that although IL-33 administration is associated with a reparative phenotype following MI, it worsens cardiac remodeling and promotes heart failure.

The Mouse Heart Attack Research Tool 1.0 database.

The generation of big data has enabled systems-level dissections into the mechanisms of cardiovascular pathology. Integration of genetic, proteomic, and pathophysiological variables across platforms and laboratories fosters discoveries through multidisciplinary investigations and minimizes unnecessary redundancy in research efforts. The Mouse Heart Attack Research Tool (mHART) consolidates a large data set of over 10 yr of experiments from a single laboratory for cardiovascular investigators to generate novel hypotheses and identify new predictive markers of progressive left ventricular remodeling after myocardial infarction (MI) in mice. We designed the mHART REDCap database using our own data to integrate cardiovascular community participation. We generated physiological, biochemical, cellular, and proteomic outputs from plasma and left ventricles obtained from post-MI and no-MI (naïve) control groups. We included both male and female mice ranging in age from 3 to 36 mo old. After variable collection, data underwent quality assessment for data curation (e.g., eliminate technical errors, check for completeness, remove duplicates, and define terms). Currently, mHART 1.0 contains >888,000 data points and includes results from >2,100 unique mice. Database performance was tested, and an example is provided to illustrate database utility. This report explains how the first version of the mHART database was established and provides researchers with a standard framework to aid in the integration of their data into our database or in the development of a similar database. NEW & NOTEWORTHY The Mouse Heart Attack Research Tool combines >888,000 cardiovascular data points from >2,100 mice. We provide this large data set as a REDCap database to generate novel hypotheses and identify new predictive markers of adverse left ventricular remodeling following myocardial infarction in mice and provide examples of use. The Mouse Heart Attack Research Tool is the first database of this size that integrates data sets across platforms that include genomic, proteomic, histological, and physiological data.

Direct cardiovascular impact of SGLT2 inhibitors: mechanisms and effects.

Diabetes is a global epidemic and a leading cause of death with more than 422 million patients worldwide out of whom around 392 million alone suffer from type 2 diabetes (T2D). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are novel and effective drugs in managing glycemia of T2D patients. These inhibitors gained recent clinical and basic research attention due to their clinically observed cardiovascular protective effects. Although interest in the study of various SGLT isoforms and the effect of their inhibition on cardiovascular function extends over the past 20 years, an explanation of the effects observed clinically based on available experimental data is not forthcoming. The remarkable reduction in cardiovascular (CV) mortality (38%), major CV events (14%), hospitalization for heart failure (35%), and death from any cause (32%) observed over a period of 2.6 years in patients with T2D and high CV risk in the EMPA-REG OUTCOME trial involving the SGLT2 inhibitor empagliflozin (Empa) have raised the possibility that potential novel, more specific mechanisms of SGLT2 inhibition synergize with the known modest systemic improvements, such as glycemic, body weight, diuresis, and blood pressure control. Multiple studies investigated the direct impact of SGLT2i on the cardiovascular system with limited findings and the pathophysiological role of SGLTs in the heart. The direct impact of SGLT2i on cardiac homeostasis remains controversial, especially that SGLT1 isoform is the only form expressed in the capillaries and myocardium of human and rodent hearts. The direct impact of SGLT2i on the cardiovascular system along with potential lines of future research is summarized in this review.

Update on the Protective Role of Regulatory T Cells in Myocardial Infarction: A Promising Therapy to Repair the Heart.

Myocardial infarction (MI) remains one of the leading causes of heart failure development and death worldwide. To date, interventional and pharmacological therapies are effective in reducing the onset of heart failure and promoting survival. However, progressive maladaptive remodeling post-MI persists in a large fraction of patients resulting in poor prognosis. Immune cell responses and an inflammatory environment largely contribute to adverse cardiac remodeling post-MI. CD4FOXP3 regulatory T cells (Tregs) are known for their immunosuppressive capacity and have been successfully implemented in multiple preclinical studies of permanent and ischemia-reperfusion MI. In this review, we highlight the important cardioprotective role of Tregs at the cardiac tissue, cellular, and molecular level, as well as the most prominent pharmacological venues that could be used to exploit Tregs as a novel therapeutic intervention to lessen myocardial injury post-MI.

Neural network predictions of (α,n) reaction cross sections at 18.5±3 MeV using the Levenberg-Marquardt algorithm.

In recent developments, artificial neural networks (ANNs) have demonstrated their capability to predict reaction cross-sections based on experimental data. Specifically, for predicting (α,n) reaction cross-sections, we meticulously fine-tuned the neural network's performance by optimizing its parameters through the Levenberg-Marquardt algorithm. The effectiveness of this approach is corroborated by notable correlation coefficients; an R-value of 0.90928 for overall correlation, 0.98194 for validation, 0.99981 for testing, and 0.94116 for the comprehensive network prediction. We conducted a rigorous comparison between the results and theoretical computations derived from the TALYS 1.95 nuclear code to validate the predictive accuracy. The mean square error value for artificial neural network results is 7620.92, whereas for TALYS 1.95 calculations, it has been found to be 50,312.74. This comprehensive evaluation process validates the reliability of the ANN based on the Levenberg-Marquardt algorithm in approximating the reaction sections, thus demonstrating its potential for comprehensive investigations. These recent developments confirm the feasibility of using ANN models to gain insight into (α,n) reaction cross-sections.

Calculation of double differential neutron cross-sections of 56Fe and 90Zr isotopes.

This study is concerned with the calculations of double differential neutron cross-sections of the structural fusion materials of 56Fe and 90Zr isotopes that are bombarded with protons. Calculations were performed using the level density models of the TALYS 1.95 code and PHITS 3.22 Monte Carlo code. Constant Temperature Fermi Gas, Back Shifted Fermi Gas, and Generalized Super Fluid Models were employed for level density models. Calculations were performed at 22.2 MeV proton energies. Calculations were compared with the experimental data taken from Experimental Nuclear Reaction Data (EXFOR). In conclusion, the results showed that the level density model results of TALYS 1.95 codes for the double differential neutron cross-sections of 56Fe and 90Zr isotopes are consistent with experimental data. On the other hand, PHITS 3.22 results gave lower cross-section values than experimental data at 120 and 150°.

Estimations for (n,α) reaction cross sections at around 14.5MeV using Levenberg-Marquardt algorithm-based artificial neural network.

Prediction of neutron-induced reaction cross-sections at around the 14.5 MeV neutron energy is crucial to calculate nuclear transmutation rates, nuclear heating, and radiation damage from gas formation in fusion reactor technology In this research, the new approach of (n,α) reaction cross-section is presented. It has been assessed by utilizing the artificial neural network (ANN) when compared to more advanced algorithms, the Levenberg-Marquardt algorithm-based ANN can be exceedingly fast. The correlation coefficients for a training R-value of 0.99283, a validation R-value of 0.991190, a testing R-value of 0.97337, and an overall R-value of 0.98515 demonstrate that Levenberg-Marquardt algorithm-based ANN is well suited for this purpose. . The obtained results were compared to theoretical calculations of TALYS 1.95 nuclear code. As a consequence, it has been demonstrated that the ANN model can be used to determine the systemic study for (n, α) reaction cross-sections.

Role of ranolazine in heart failure: From cellular to clinic perspective.

Ranolazine was approved by the US Food and Drug Administration as an antianginal drug in 2006, and has been used since in certain groups of patients with stable angina. The therapeutic action of ranolazine was initially attributed to inhibitory effects on fatty acids metabolism. As investigations went on, however, it developed that the main beneficial effects of ranolazine arise from its action on the late sodium current in the heart. Since late sodium currents were discovered to be involved in various heart pathologies such as ischemia, arrhythmias, systolic and diastolic dysfunctions, and all these conditions are associated with heart failure, ranolazine has in some way been tested either directly or indirectly on heart failure in numerous experimental and clinical studies. As the heart continuously remodels following any sort of severe injury, the inhibition by ranolazine of the underlying mechanisms of cardiac remodeling including ion disturbances, oxidative stress, inflammation, apoptosis, fibrosis, metabolic dysregulation, and neurohormonal impairment are discussed, along with unresolved issues. A projection of pathologies targeted by ranolazine from cellular level to clinical is provided in this review.

Sex differences in cardiac remodeling post myocardial infarction with acute cigarette smoking.

BACKGROUND: Whether cigarette smoking affects the heart post-myocardial infarction (MI) in a sex-dependent way remains controversial. Using a mouse model, we investigated cardiac remodeling under the influence of acute cigarette smoke (CS) exposure following ischemic injury in both sexes. METHODS: Ten cigarettes were smoked twice daily for 2 weeks followed by MI and then 1 additional week post permanent LAD ligation. Cardiac function, histology, and infarct size were assessed, and inflammatory markers quantified by RT-PCR. Statistical comparisons were performed using an unpaired t test or ANOVA followed by Tukey post hoc test. RESULTS: We observed that cigarette smoking exacerbated both left and right ventricular remodeling only in males at an early stage of post-MI. Females did not display a significant structural and/or functional alteration within 7 days of cardiac remodeling post-MI upon CS exposure. Worsened right ventricular remodeling in males was independent of pulmonary congestion. CS-exposed males exhibited enhanced increases in left ventricular end systolic and diastolic volumes, as well as reductions in ejection fraction and fractional area changes of left ventricular base. At day 7, infarct size was increased by cigarette smoking in males only, which was accompanied by enhanced collagen deposition in both the infarcted and peri-infarcted areas. Both IL-6 and TNF-α mRNA expression significantly increased in CS-exposed MI male group only at day 7 post-MI suggestive of prolonged inflammation. CONCLUSIONS: These findings indicate that CS exposure worsens the progression of cardiac remodeling post-MI in male sex in a significant manner compared to female sex at least at early stages.

Genomic, Proteomic, and Metabolic Comparisons of Small Animal Models of Heart Failure With Preserved Ejection Fraction: A Tale of Mice, Rats, and Cats.

Heart failure with preserved ejection fraction (HFpEF) remains a medical anomaly that baffles researchers and physicians alike. The overall phenotypical changes of diastolic function and left ventricular hypertrophy observed in HFpEF are definable; however, the metabolic and molecular alterations that ultimately produce these changes are not well established. Comorbidities such as obesity, hypertension, and diabetes, as well as general aging, play crucial roles in its development and progression. Various animal models have recently been developed to better understand the pathophysiological and metabolic developments in HFpEF and to illuminate novel avenues for pharmacotherapy. These models include multi-hit rodents and feline aortic constriction animals. Recently, genomic, proteomic, and metabolomic approaches have been used to define altered signaling pathways in the heart associated with HFpEF, including those involved in inflammation, cGMP-related, Ca2+ handling, mitochondrial respiration, and the unfolded protein response in endoplasmic reticulum stress. This article aims to present an overview of what has been learnt by these studies, focusing mainly on the findings in common while highlighting unresolved issues. The knowledge gained from these research models will not simply be of benefit for treating HFpEF but will undoubtedly provide new insights into the mechanisms by which the heart deals with external stresses and how the processes involved can fail.

True left ventricular aneurysm after blunt chest trauma.

Left ventricular aneurysms are common in clinical practice. Although their underlying aetiology is generally clear by the clinical context, it can be hard to define the exact cause in some cases. We report a case of a patient in whom cardiac MRI provided important information about the differential diagnosis of a left ventricular aneurysm.

Estimations of giant dipole resonance parameters using artificial neural network.

In this study; Giant Dipole Resonance (GDR) parameters of the spherical nucleus have been estimated by using artificial neural network (ANN) algorithms. The ANN training has been carried out with the Levenberg-Marquardt feed-forward algorithm in order to provide fast convergence and stability in ANN training and experimental data, taken from Reference Input Parameter Library (RIPL). R values of the system have been found as 0.99636, 0.94649, and 0.98318 for resonance energy, full width half maximum, and resonance cross-section, respectively. Obtained results have been compared with the GDR parameters which are taken from the literature. To validate our findings, newly acquired GDR parameters were then replaced with the existing GDR parameters in the TALYS 1.95 code and 142-146Nd(γ,n)141-145Nd reaction cross-sections have been calculated and compared with the experimental data taken from the literature. As a result of the study, it has been shown that ANN algorithms can be used to calculate the GDR parameters in the absence of the experimental data.

Estimations of level density parameters by using artificial neural network for phenomenological level density models.

The main aim of this study is to develop accurate artificial neural network (ANN) algorithms to estimate level density parameters. An efficient Bayesian-based algorithm is presented for classification algorithms. Unknown model parameters are estimated using the observed data, from which the Bayesian-based algorithm is predicted. This paper focuses on the Bayesian method for parameter estimations of Gilbert Cameron Model (GCM), Back Shifted Fermi Gas Model (BSFGM) and Generalised Super Fluid Model (GSM), which are known as the phonemological level density models. Obtained level density parameters have been compared with the Reference Input Parameter Library for Calculation of Nuclear Reactions and Nuclear Data Evaluations (RIPL) data. R values of the Bayesian method have been found as 0.9946, 0.9981 and 0.9824 for BSFGM, GCM and GSM, respectively. In order to validate our results, default level density parameters of TALYS 1.95 code have been changed with our newly obtained results and photo-neutron cross-section calculations of the 117Sn(γ,n)116Sn, 118Sn(γ,n)117Sn, 119Sn(γ,n)118Sn and 120Sn(γ,n)119Sn reactions have been calculated by using these newly obtained level density parameters.

Distorted assessment of left atrial size by echocardiography in patients with increased aortic root diameter.

BACKGROUND: Left atrial (LA) size is frequently assessed by posterior-anterior linear measurement of LA (LAD P-A) in the parasternal long axis to expedite examination. Aging, changes in body surface area, and several cardiovascular pathologies can affect aortic root (AoR) size, thereby affecting LA anatomical shape. We hypothesized that AoR dilatation influences LAD P-A and consequently correct assessment of LA size. RESULTS: We tested our hypothesis in a study of 70 patients with AoR diameter ranging from 2.7 to 4.8 cm. LA size assessed in parasternal long axis view as LAD P-A was compared to that with LA width and length acquired in the apical two and four chamber view. Simpson's method of discs was used as standard measurement to assess LA volume. We observed that LAD P-A in the parasternal long axis decreases when AoR diameter increases. Thus, the increase in LA size assessed in parasternal long axis did not correlate with the increase of LA volume. Further analysis revealed that a significant positive correlation was observed when LAV was plotted as a function of LAD P-A only for those with a normal size AoR. In contrast, LA volume increase correlated with LA diameters assessed in the apical two and four chamber view regardless of AoR size. CONCLUSIONS: Our study documents that increases in AoR impact on the linear measurement of LA, resulting in an underestimated LAD P-A. LA size ought to be calculated from the apical two and four chambers view parameters, especially in patients with AoR dilatation.

Sex-based differences in myocardial infarction-induced kidney damage following cigarette smoking exposure: more renal protection in premenopausal female mice.

The impact of cigarette smoking (CS) on kidney homeostasis in the presence of myocardial infarction (MI) in both males and females remains poorly elucidated. C57BL6/J mice were exposed to 2 weeks of CS prior to MI induction followed by 1 week of CS exposure in order to investigate the impact of CS on kidney damage in the presence of MI. Cardiac hemodynamic analysis revealed a significant decrease in ejection fraction (EF) in CS-exposed MI male mice when compared with the relative female subjects, whereas cardiac output (CO) comparably decreased in CS-exposed MI mice of both sexes. Kidney structural alterations, including glomerular retraction, proximal convoluted tubule (PCT) cross-sectional area, and total renal fibrosis were more pronounced in CS-exposed MI male mice when compared with the relative female group. Although renal reactive oxygen species (ROS) generation and glomerular DNA fragmentation significantly increased to the same extent in CS-exposed MI mice of both sexes, alpha-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) significantly increased in CS-exposed MI male mice, only. Metabolically, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide riboside-1 (NMRK-1) substantially increased in CS-exposed MI female mice only, whereas sirtuin (SIRT)-1 and SIRT-3 substantially decreased in CS-exposed MI male mice compared with their relative female group. Additionally, renal NAD levels significantly decreased only in CS-exposed MI male mice. In conclusion, MI female mice exhibited pronounced renal protection following CS when compared with the relative male groups.

Gender-biased kidney damage in mice following exposure to tobacco cigarette smoke: More protection in premenopausal females.

Multiple clinical studies documented renal damage in chronic cigarette smokers (CS) irrespective of their age and gender. Premenopausal female smokers are known to exert a certain cardiovascular and renal protection with undefined mechanisms. Given the multiple demographic variables within clinical studies, this experimental study was designed to be the first to assess whether gender-biased CS-induced kidney damage truly exists between premenopausal female and age-matched C57Bl6J male mice when compared to their relative control groups. Following 6 weeks of CS exposure, cardiac function, inflammatory marker production, fibrosis formation, total and glomerular ROS levels, and glomerulotubular homeostasis were assessed in both genders. Although both CS-exposed male and female mice exhibited comparable ROS fold change relative to their respective control groups, CS-exposed male mice showed a more pronounced fibrotic deposition, inflammation, and glomerulotubular damage profile. However, the protection observed in CS-exposed female group was not absolute. CS-exposed female mice exhibited a significant increase in fibrosis, ROS production, and glomerulotubular alteration but with a pronounced anti-inflammatory profile when compared to their relative control groups. Although both CS-exposed genders presented with altered glomerulotubular homeostasis, the alteration phenotype between genders was different. CS-exposed males showed a significant decrease in Bowman's space along with reduced tubular diameter consistent with an endocrinization pattern of chronic tubular atrophy, suggestive of an advanced stage of glomerulotubular damage. CS-exposed female group, on the other hand, displayed glomerular hypertrophy with a mild tubular dilatation profile suggestive of an early stage of glomerulotubular damage that generally precedes collapse. In conclusion, both genders are prone to CS-induced kidney damage with pronounced female protection due to a milder damage slope.