Hemicyanine-Based Highly Water-soluble Probe for Extracellular Nitroreductase.

Nitroreductase (NTR) has long been a target of interest for its important role involved in the nitro compounds metabolism. Various probes have been reported for NTR analysis, but rarely able to distinguish the extracellular NTR from intracellular ones. Herein we reported a new NTR sensor, HCyS-NO2, which was a hemicyanine molecule with one nitro and two sulfo groups attached. The nitro group acted as the reporting group to respond NTR reduction. Direct linkage of nitro group into the hemicyanine π conjugate system facilitated the intramolecular electron transfer (IET) process and thus quenched the fluorescence of hemicyanine core. Upon reduction with NTR, the nitro group was rapidly converted into the hydroxylamino and then the amino group, eliminating IET process and thus restoring the fluorescence. The sulfo groups installed significantly increased the hydrophilicity of the molecule, and introduced negative charges at physiological pH, preventing the diffusion into bacteria. Both gram-negative and gram-positive bacteria were able to turn on the fluorescence of HCyS-NO2, without detectable diffusion into cells, providing a useful tool to probe the extracellular reduction process.

Cell-Selective Multifunctional Surface Covalent Reconfiguration Using Aptamer-Enabled Proximity Catalytic Labeling.

Cell surface engineering provides access to custom-made cell interfaces with desirable properties and functions. However, cell-selective covalent labeling methods that can simultaneously install multiple molecules with different functions are scarce. Herein, we report an aptamer-enabled proximity catalytic covalent labeling platform for multifunctional surface reconfiguration of target cells in mixed cell populations. By conjugating peroxidase with cell-selective aptamers, the probes formed can selectively bind target cells and catalyze target-cell-localized covalent labeling in situ. The universal applicability of the platform to different phenol-modified functional molecules allows us to perform a variety of manipulations on target cells, including labeling, tracking, assembly regulation, and surface remodeling. In particular, the platform has the ability of multiplexed covalent labeling, which can be used to install two mutually orthogonal click reactive molecules simultaneously on the surface of target cells. We thus achieve "multitasking" in complex multicellular systems: programming and tracking specific cell-cell interactions. We further extend the functional molecules to carbohydrates and perform ultrafast neoglycosylation on target living cells. These newly introduced sugars on the cell membrane can be recognized and remodeled by a glycan-modifying enzyme, thus providing a method package for cell-selective engineering of the glycocalyx.

Interception Proximity Labeling for Interrogating Cell Efflux Microenvironment.

The difficulty in elucidating the microenvironment of extracellular H2O2 efflux has led to the lack of a critical extracellular link in studies of the mechanisms of redox signaling pathways. Herein, we mounted horseradish peroxidase (HRP) to glycans expressed globally on the living cell surface and constructed an interception proximity labeling (IPL) platform for H2O2 efflux. The release of endogenous H2O2 is used as a "physiological switch" for HRP to enable proximity labeling. Using this platform, we visualize the oxidative stress state of tumor cells under the condition of nutrient withdrawal, as well as that of macrophages exposed to nonparticulate stimuli. Furthermore, in combination with a proteomics technique, we identify candidate proteins at the invasion interface between fungal mimics (zymosan) and macrophages by interception labeling of locally accumulated H2O2 and confirm that Toll-like receptor 2 binds zymosan in a glycan-dependent manner. The IPL platform has great potential to elucidate the mechanisms underlying biological processes involving redox pathways.

Silencing HIF-1α aggravates growth inhibition and necrosis of proximal renal tubular epithelial cell under hypoxia.

The kidney is particularly susceptible to ischemia/hypoxia insult while dysfunction of proximal tubular epithelial cells (PTEC) is a primary pathologic hallmark in acute kidney injury. Hypoxia-inducible factor-1 (HIF-1) is a key regulator responsible for cellular hypoxic responses. Therefore, we investigated the effects of HIF-1 suppression, using small interference RNA (siRNA), upon the cell fate of PTEC under hypoxia, and explored the underlying possible molecular mechanism. Hypoxia was induced with hypoxia mimetic cobalt chloride. Our data showed that, in HIF-1α siRNA group, the HK-2 cells growth inhibition and necrosis became worse than those in hypoxia group. However, for apoptosis, no significant difference was observed between them. Consistent with the downregulation of HIF-1α in HIF-1α siRNA group, both mRNA and protein expression of glucose transporter-1 (Glut-1) and vascular endothelial growth factor (VEGF) also reduced more significantly than those in hypoxia group. In conclusion, silencing HIF-1α gene could aggravate growth inhibition and necrosis of PTEC under hypoxia. We provide evidence, from the opposite direction, that HIF-1 activation under hypoxia may facilitate adaptation and survival of proximal renal tubular cells, and the beneficial effects may be related to its downstream genes, such as Glut-1 and VEGF.

ELISA examining urinary angiotensinogen as a potential indicator of intrarenal renin-angiotensin system (RAS) activity: a clinical study of 128 chronic kidney disease patients.

In the current study, we measured urinary angiotensinogen (AGT) through enzyme-linked immunoadsordent assay (ELISA) and analyzed its correlation with intrarenal renin-angiotensin system (RAS) activity in 128 chronic kidney disease (CKD) patients. Urinary and plasma renin activity, AGT, angiotensin II (Ang II) and aldosterone levels were also measured by radioimmunoassay (RIA) or ELISA in these participants. Further, the expression level of intrarenal renin, AGT, Ang II and Ang II receptors were examined by immunohistochemistry staining (IHCS) in 72 CKD patients. Their correlations with urinary AGT were also analyzed. We found that the urinary AGT level was positively correlated with hypertension (ρ = 0.28, P < 0.01), urinary protein (r = 0.38, P < 0.01), urinary Ang II (r = 0.29, P < 0.05), urinary type IV collagen (Col IV) (r = 0.56, P < 0.01), and was negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.28, P < 0.01), urinary sodium (r = -0.22, P < 0.05) and serum AGT (r = -0.27, P < 0.01). Multiple regression analysis indicated low serum AGT (P < 0.01), high urinary protein (P < 0.01), high urinary Ang II (P < 0.05) and high urinary Col IV (P < 0.01) were correlated significantly with high urinary AGT. Urinary AGT level was positively correlated with intrarenal expression level of AGT (ρ = 0.46, P < 0.01), Ang II (ρ = 0.56, P < 0.01) and Ang II type 1 receptor (ρ = 0.32, P < 0.01), as detected by IHCS. Together, these data suggest that urinary AGT might be a potential biomarker of intrarenal RAS and Ang II activities in CKD patients.

Site-selected in situ polymerization for living cell surface engineering.

The construction of polymer-based mimicry on cell surface to manipulate cell behaviors and functions offers promising prospects in the field of biotechnology and cell therapy. However, precise control of polymer grafting sites is essential to successful implementation of biomimicry and functional modulation, which has been overlooked by most current research. Herein, we report a biological site-selected, in situ controlled radical polymerization platform for living cell surface engineering. The method utilizes metabolic labeling techniques to confine the growth sites of polymers and designs a Fenton-RAFT polymerization technique with cytocompatibility. Polymers grown at different sites (glycans, proteins, lipids) have different membrane retention time and exhibit differential effects on the recognition behaviors of cellular glycans. Of particular importance is the achievement of in situ copolymerization of glycomonomers on the outermost natural glycan sites of cell membrane, building a biomimetic glycocalyx with distinct recognition properties.

Transient hypoxia-inducible factor activation in rat renal ablation and reduced fibrosis with L-mimosine.

AIM: Hypoxia-inducible factor (HIF) activity during the course of chronic kidney disease (CKD) development is poorly defined, and the effect of HIF activation on CKD is still controversial. The purpose of the present study was to characterize HIF expression during the course of CKD development, and to investigate the effect of HIF activation on CKD by using prolyl hydroxylase (PHD) inhibitor L-mimosine. METHODS: Rats with remnant kidneys (RK) were killed at week 1, 2, 4, 6, 8, 12 after subtotal nephrectomy. An additional group of RK rats was treated with L-mimosine to study the effect of HIF-α activation. RESULTS: Tubulointerstitial hypoxia in the remnant kidney began at week 1 and continued, albeit attenuated, until week 12, the last time point examined. The nuclear expression of HIF-1α and HIF-2α, as well as typical HIF target genes VEGF (vascular endothelial growth factor), HO-1 (heme oxygenase-1), GLUT-1 (glucose transporter-1) and EPO (erythropoietin), were all upregulated in the early stage of RK when renal function was stable, and returned to the basal level later, accompanied by impaired renal function and interstitial fibrosis. L-mimosine administered from week 5 to week 12 led to accumulation of HIF-1α and HIF-2α proteins, increased expression of VEGF, HO-1 and GLUT-1, and improved renal function. Furthermore, fibrosis markers α-smooth muscle actin (α-SMA) and Collagen III, as well as peritubular capillary rarefaction index, were all significantly decreased after L-mimosine treatment. CONCLUSION: There was a transient HIF-α activation in the remnant kidney of rats at the early stage following subtotal nephrectomy. L-mimosine administered in later stages re-activated HIF-α and reduced tubulointerstitial fibrosis.

[The prevalence and risk factors of kidney disease in type 2 diabetic patients in rural Shanghai].

OBJECTIVE: To identify the prevalence and etiology of kidney disease and the related risk factors in type 2 diabetic patients in rural Shanghai. METHODS: A cross-sectional study in type 2 diabetic patients was conducted in a community of Shanghai. Questionnaire, clinical examination and laboratory tests were completed to collect the information about sociodemographic and healthcare characteristics. RESULTS: A total of 1421 eligible patients with complete information were screened from 1487 type 2 diabetic patients between November 2008 and March 2009. Of them, 40.75% were men, 59.25% were women, aged 37 - 86 (61.33 ± 9.65) years old, with diabetic duration of 0.25 - 43.92 (7.85 ± 6.34) years. Among them, 43.42% had diabetic retinopathy, 21.18% had neuropathy; 69.95% met the screening definition for hypertension, 76.07% for hyperlipidemia, 15.55% for hyperuricemia and 23.65% for cardiovascular disease. The control rates of fasting blood glucose, glycosylated hemoglobin, blood pressure and serum cholesterol were 57.71%, 33.99%, 14.22% and 2.46%, respectively. The prevalence of kidney disease, diabetic nephropathy and non-diabetic renal disease was 41.31%, 18.51% and 13.44%, respectively; and 9.36% were diagnosed as renal insufficiency of unknown reasons. Age, diabetic duration, hyperuricemia, diabetic retinopathy and poor control of blood pressure were independently associated with kidney disease; age and poor control of blood pressure were independently associated with diabetic nephropathy; age and hyperuricemia were independent risk factors of renal insufficiency in patients with diabetic nephropathy. CONCLUSIONS: Although the diabetic duration of these subjects is relatively short, the prevalence of complications including diabetic nephropathy is high. The high prevalence of non-diabetic renal disease shows the importance of further screening and diagnoses for prevention. Strict control of blood glucose, blood pressure, serum cholesterol and serum uric acid are key points of cutting down the prevalence of diabetic nephropathy and chronic kidney disease.

Highly sensitive and fast-response ethanol sensing of porous Co3O4 hollow polyhedra via palladium reined spillover effect.

Highly sensitive and fast detection of volatile organic compounds (VOCs) in industrial and living environments is an urgent need. The combination of distinctive structure and noble metal modification is an important strategy to achieve high-performance gas sensing materials. In addition, it is urgent to clarify the chemical state and function of noble metals on the surface of the sensing material during the actual sensing process. In this work, Pd modified Co3O4 hollow polyhedral (Pd/Co3O4 HP) is developed through one-step pyrolysis of a Pd doped MOF precursor. At an operating temperature of 150 °C, the Pd/Co3O4 HP gas sensor can achieve 1.6 times higher sensitivity than that of Co3O4 HP along with fast response (12 s) and recovery speed (25 s) for 100 ppm ethanol vapor. Near-ambient pressure X-ray photoelectron spectroscopy (NAPXPS) was used to monitor the dynamic changes in the surface state of Pd/Co3O4 HP. The NAPXPS results reveal that the oxidation and reduction of Pd in the ethanol sensing process are attributed to a spillover effect of oxygen and ethanol, respectively. This work opens up an effective approach to investigate spillover effects in a sensing mechanism of noble metal modified oxide semiconductor sensors.

Serum uric acid is inversely related to acute ischemic stroke morbidity in hemodialysis patients.

AIM: Elevated serum uric acid (sUA) is usually associated with a high occurrence of acute ischemic stroke (AIS) in the general population. The aim of this study is to evaluate the role of sUA in AIS among hemodialysis (HD) patients. METHODS: We followed up the occurrence of AIS in 226 HD patients for 18 months from January 2009 to June 2010. The parameters included demographic characteristics, duration of HD, sUA, serum albumin, and other parameters. Logistic regression was performed to evaluate the function of SUC levels in the occurrence of AIS. RESULTS: A total of 43 patients suffered from AIS. By univariate logistic regression analysis an inverse association was observed in sUA level with the risk of AIS (p = 0.005), but the significance of this inverse association was attenuated while adjusted for age, gender and pulse pressure (PP) (p = 0.029), and even weakened while adjusted for age, gender, PP and diabetes nephropathy (DN) (p = 0.065), and finally abolished after adjustment for age, gender, PP, DN, hsCRP and pre-albumin. CONCLUSION: This study indicates an inverse association between sUC and the occurrence of AIS in HD patients. Demographic characteristics and malnutrition-microinflammation syndrome seem to play a significant role in this association.

BMI, spKt/V, and SBP but not DBP are related to LVH in Chinese maintenance hemodialysis patients.

OBJECTIVE: Left ventricular hypertrophy (LVH) is the strongest predictor of cardiovascular mortality, the leading cause of death in hemodialysis (HD) patients. This study aims to identify the potential risk factors for LVH in HD patients. METHODS: Exactly, 164 patients (84 men and 80 women) who had been on HD treatment for at least 6 months were enrolled. Clinical data were collected. Anthropometric measurements, biochemical analyses, and echocardiography were performed. The risk factors were determined by multivariate linear and logistic regression. RESULTS: In all the patients, the prevalence of LVH was 66.5%. The patients with LVH had higher body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure, and lower single-pool kt/V (spKt/V) compared with those without LVH. Multivariate linear regression showed that BMI (ß = 7.608, p = 0.014), SBP (ß = 9.462, p = 0.001), and spKt/V (ß = -14.226, p = 0.024) were independently correlated with left ventricular mass index (LVMI). Multivariate logistic regression showed the same results that BMI (ß = 7.193, p = 0.032), SBP (ß = 9.382, p = 0.02), and spKt/V (ß = -12.535, p = 0.001) were independently correlated with LVH. CONCLUSIONS: In Chinese maintenance hemodialysis patients, BMI, single-pool Kt/V (spKt/V), and SBP were independently correlated with left ventricular mass index and were independent risk factors for LVH.

Acute kidney injury in a Chinese hospitalized population.

OBJECTIVES: This study's objective was to determine the incidence and mortality rate of acute kidney injury (AKI) among hospitalized adult patients in a tertiary metropolitan hospital of China, and to evaluate the impact of AKI on in-hospital mortality, cost and length of stay (LOS). METHODS: Patients who were admitted to Zhongshan Hospital, Fudan University, Shanghai, China between September 1st, 2004 and June 30th, 2008 were involved. The presence and severity of AKI were assessed using absolute and relative increases from baseline to peak serum creatinine concentration during hospitalization. AKI was defined as a relative 50% increase or an absolute increment of 0.3 mg/dl (26.5 µmol/l) in serum creatinine within 48 h. After screening the computer-based data on kidney function, patients with AKI were identified and further history reviews were performed to obtain information regarding patients' demography, prognosis, severity of kidney injury and causes of AKI. RESULTS: There were 176,155 admissions during the study period and 5,619 met the diagnostic criteria of AKI. The overall incidence rate of AKI was 3.19%. Cardiovascular diseases followed by urogenital diseases and malignancy were the most common admission diagnoses. In-hospital mortality rate was 2.84% in all discharges and 19.68% in patients with AKI. Of AKI patients, old age, intensive care unit admission, Acute Kidney Injury Network score, need for renal replacement therapy and organ system failure number were independent predictors of hospital mortality according to forward conditional logistic regression. CONCLUSIONS: AKI is prevalent in the Chinese hospitalized patients. Slight elevations of serum creatinine are associated with significantly increased mortality, LOS and hospital cost. Moreover, outcomes are related directly to the severity of AKI characterized by percent changes in serum creatinine.

Expanding the scope of chemiluminescence in bioanalysis with functional nanomaterials.

Nanomaterial-enabled chemiluminescence (CL) detection has become a growing area of interest in recent years. We review the development of nanomaterial-based CL detection strategies and their applications in bioanalysis. Much progress has been achieved in the past decade, but most attempts still remain in the proof-of-concept stage. This review highlights recent advances in nanomaterials in CL detection and organizes them into three groups based on their role in detection: as a sensing platform, as a signal probe, and applications in homogeneous systems. Furthermore, we have discussed the critical challenges we are facing and future prospects of this field.

Multiplex immunoassay of chicken cytokines via highly-sensitive chemiluminescent imaging array.

Quantitative detection of multiple chicken cytokines is a good evaluation of cell-mediated immunity in chickens after disease infection or vaccination. However, current assay methods for chicken cytokines cannot meet the needs of clinical diagnosis due to unsatisfactory sensitivity and low assay throughput. Herein, a sensitive chemiluminescence (CL) imaging immunosensor array has been developed for high-throughput detection of multiple chicken cytokines. The chicken cytokines immunosensor array was prepared by assembling different cytokine capture antibodies onto a disposable silanized glass chip, where horseradish peroxidase and antibody-conjugated gold nanoparticles were used as multienzymatic amplification probe for CL imaging signal amplification. By using a sandwich assay mode, the amplified CL signals from each sensing array cell were collected for quantitation. Using chicken interleukin-4 and chicken interferon-γ as model cytokines, this novel multiplexed and amplified method demonstrated simultaneous measurement of the two chicken cytokines in the linear ranges of 0.008-0.12 ng/mL and 0.005-0.20 ng/mL, respectively, which yields limits of detection down to 2 pg/mL and 3 pg/mL. The CL imaging array method reported here also demonstrated high specificity, good repeatability, and high stability and accuracy, providing a novel multiplex immunoassay strategy for highly sensitive and high-throughput detection of chicken cytokines and further disease diagnosis in poultry.

A nanozyme tag enabled chemiluminescence imaging immunoassay for multiplexed cytokine monitoring.

We report a new concept of a chemiluminescence imaging nanozyme immunoassay (CINIA), in which nanozymes are exploited as catalytic tags for simultaneous multiplex detection of cytokines. The CINIA provides a novel and universal nanozyme-labeled multiplex immunoassay strategy for high-throughput detection of relevant biomarkers and further disease diagnosis.

Prolyl hydroxylase 2 (PHD2) inhibition protects human renal epithelial cells and mice kidney from hypoxia injury.

Prolyl hydroxylase domain protein 2 (PHD2) is a key oxygen sensor, setting low steady-state level of hypoxia-inducible factor-α (HIF-α). Here, we showed that treatment of cobalt chloride (CoCl2), a hypoxia mimic, in HK-2 tubular epithelial cells induced PHD2 and HIF-1/2α expression as well as cell apoptosis and autophagy activation. Three methyladenine (3-MA), the autophagy inhibitor, blocked autophagy and protected HK-2 cells from CoCl2. Significantly, siRNA knockdown of PHD2 also protected HK-2 cells from CoCl2,possibly via increasing HIF-1α expression. Reversely, HIF-1α siRNA knockdown almost abolished cytoprotection by PHD2 siRNA in CoCl2-treated HK-2 cells. In vivo, pretreatment with a PHD inhibitor L-mimosine remarkably attenuated mice renal ischemia-reperfusion injuries. Molecularly, L-mimosine inhibited apoptosis and inflammatory responses in injured mice kidneys. Together, our results suggest that PHD2 silence or inhibition protects human renal epithelial cells and mice kidney from hypoxia injuries.

Bladder epithelial cell proliferation of rats induced by terephthalic acid-calculi.

OBJECTIVE: Urinary bladder hyperplasia associated with terephthalic acid (TPA) treatment was examined with concomitant use of sodium bicarbonate (NaHCO3) or hydrochlorothiazide to allow assessment of the relationship among bladder stones, epithelial hyperplasia, and corresponding cell cycle checkpoint gene expression in Sprague-Dawley (SD) rat. METHODS: A total of 112 weanling male SD rats that divided between six groups were given basal diet (control), diets containing 5% TPA or in combination with either 4% sodium NaHCO3 or 0.02% hydrochlorothiazide. After 90-day feeding, bladder samples were collected for histopathological diagnoses, and immunohistochemical method was used to characterize the expression of p16Ink4a cyclin D1, CDK4, EGFr and cyclin E in relation to that of proliferating cell nuclear antigen (PCNA). RESULTS: In TPA treatment groups, bladder stone incidence was 40% (21/52) with 14 cases of proliferative bladder. In control and other groups, neither stone nor epithelial cell proliferation was diagnosed. PCNA-positive focal hyperplasic lesions involved all epithelial layers. Overexpressions of cyclin D1, CDK4, EGFr are found in the corresponding lesion. p16Ink4a nuclear staining reduced in proliferative bladders especially with a great quantity of stone. In addition, no positive expression was detected on cyclin E. CONCLUSION: The present study provides a strong evidence of a link between induction of bladder hyperplasia, deregulation of the p16Ink4a-cyclin D1/CDK4 pathway, and abnormal EGFr mediated signal transduction pathway.

Association of indoxyl sulfate with heart failure among patients on hemodialysis.

BACKGROUND AND OBJECTIVES: Indoxyl sulfate, a protein-bound uremic toxin, may be associated with cardiovascular events and mortality in patients with CKD. This study aimed to investigate the relationship between indoxyl sulfate and heart failure in patients on hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients on hemodialysis for >6 months were enrolled within 6 months. Patients with congestive heart failure, angina pectoris, acute myocardial infarction, cerebral infarction, or cerebral hemorrhage within 3 months before the study or those <18 years old were excluded. The primary end point was first heart failure event during follow-up. RESULTS: In total, 258 patients (145 men) with a mean age of 57.0 ± 14.6 years old were enrolled. Median plasma indoxyl sulfate level was used to categorize patients into two groups: the low-indoxyl sulfate group (indoxyl sulfate ≤ 2.35 µg/ml) and the high-indoxyl sulfate group (indoxyl sulfate >32.35 µg/ml). Then, patients were prospectively followed up for a median of 48.0 (interquartile range: 33.5-48.0) months. During follow-up, 68 patients experienced episodes of first heart failure. Kaplan-Meier analysis revealed the incidence of first heart failure event in the high-indoxyl sulfate group was significantly higher than in the low-indoxyl sulfate group (log rank P<0.001). Cox regression analysis showed indoxyl sulfate was significantly associated with first heart failure event (indoxyl sulfate as the continuous variable: hazard ratio, 1.02; 95% confidence interval [95% CI], 1.01 to 1.03; P=0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 3.49; 95% CI, 1.97 to 6.20; P<0.001). After adjustment for other confounding factors, the results remained significant (indoxyl sulfate as the continuous variable: hazard ratio, 1.04; 95% CI, 1.02 to 1.06; P<0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 5.31; 95% CI, 2.43 to 11.58; P<0.001). CONCLUSIONS: Plasma indoxyl sulfate was associated with first heart failure event in patients on hemodialysis. Whether indoxyl sulfate is only a biomarker or involved in the pathogenesis of heart failure in hemodialysis warrants additional study.

The protection of selenium on cadmium-induced inhibition of spermatogenesis via activating testosterone synthesis in mice.

Selenium (Se) is an essential trance element in testis. However, the potential protective effects of Se against cadmium (Cd)-induced reproductive toxicity remained to be elucidated. Male ICR mice were orally administered by gavage with Na2SeO3 (0.1, 0.2, 0.4 mg/kg BW) for 1h prior to CdCl2 (5 mg/kg BW) alone or in combination for 15, 25 or 35 days. Cd exposure caused a significant decrease in body weight, sperm concentration and motility as well as plasma testosterone level which was accompanied by decreased antioxidant enzymatic activity of SOD and GSH-Px and by increased lipid peroxidation (as malondialdehyde, MDA). Se pretreatment compensated deficits in the sperm parameters (concentration, motility and morphology) induced by Cd. Se (0.4 mg/kg BW) treatment significantly increased serum testosterone level that was reduced by Cd (on 15th, 25th and 35th day) (P<0.01). Se treatment ameliorated Cd-induced reduction in testicular steroidogenic acute regulatory (StAR) and 17ß-hydroxysteroid dehydrogenase (17ß-HSD) activities. The present study suggest that the protective potential of Se against Cd-induced reprotoxicity might be due to up-regulation StAR and testosterone synthetic enzyme activity, which could be useful for increasing testosterone synthesis for achieving optimum protection in sperm quality and spermatogenesis.