Advancements in research on lactate dehydrogenase A in urinary system tumors.

Tumors of the urinary system, such as prostate cancer, bladder cancer, and renal cell carcinoma, are among the most prevalent types of tumors. They often remain asymptomatic in their early stages, with some patients experiencing recurrence or metastasis post-surgery, leading to disease progression. Lactate dehydrogenase A (LDHA) plays a crucial role in the glycolysis pathway and is closely associated with anaerobic glycolysis in urinary system tumors. Therefore, a comprehensive investigation into the intricate mechanism of LDHA in these tumors can establish a theoretical foundation for early diagnosis and advanced treatment. This review consolidates the current research and applications of LDHA in urinary system tumors, with the aim of providing researchers with a distinct perspective.

Renal tubular damage caused by cylindrospermopsin (cyanotoxin) in mice.

Cylindrospermopsin (CYN) is a cyanotoxin and a hydrophilic alkaloid of 415 Da. The principal effect of CYN is the inhibition of protein synthesis, and it can damage various organs. Studies have demonstrated that the kidney is the most affected organ. CYN has played roles in at least two poisoning cases, i.e., the mysterious Palm Island disease in Australia and the event at Caruaru in Brazil. Therefore, we aimed to determine how CYN disrupts the renal tissue. Dose-response curves following single intraperitoneal injections of purified CYN (at 0, 16, 32, 64 and 128 µg CYN/kg body weight) were created in 10-week-old male BALB/C mice (n = 4). Renal physiology parameters were analyzed after 7 and 14 days. However, no alterations in the glomerular filtration rate (GFR) or nephrin expression (a crucial protein for glomerular integrity) were observed. We detected low-molecular-weight proteinuria and increased excretions of the tubular enzymes lactate dehydrogenase (LDH) and gamma-glutamyl transferase (GGT) at doses of 16, 32 and 64 µg CYN/kg body weight. Furthermore, we observed increases in the renal interstitial space and collagen deposition that indicated edema and fibrosis. The data seem to indicate that the damage is in the proximal tubule.

Nephroprotective property of Cinnamomum zeylanicum and its antibacterial activity in combination with gantamicin.

Cinnamomum zeylanicum has strong antioxidant properties and has been presented to have nephroprotective effects. Present work was aimed to study the nephroprotective property of the plant extract through urinary enzymes excretion, to confirm its protective effects and to observe the antibacterial activities of gentamicin in combination with the plant extract. 200mg/kg/day of the plant extracts were administered alone and as co-therapy with gentamicin. Urinary lactate dehydrogenase (LDH) and Urinary alkaline phospatase (ALP) excretions were observed through reagents kits with the help of Power-Lab 300. Antibacterial activities were assessed for gentamicin alone and in combination with the extract. Present study showed that the plant extract have excess quantity of flavonoids, which may responsible for attenuating the excessive excretion of urinary LDH. However, Urinary ALP excretion was found remained same throughout the study period in all experimental groups; might be detected in acute damage. Further, the plant also proved to have no decreasing impact on the antibacterial activities of gentamicin.

In situ lactate dehydrogenase activity: a novel renal cortical imaging biomarker of tubular injury?

Renal ischemia-reperfusion injury is the state of which a tissue experiences injury after a phase of restrictive blood supply and recirculation. Ischemia-reperfusion injury (I/R-I) is a leading cause of acute kidney injury (AKI) in several disease states, including kidney transplantation, sepsis, and hypovolemic shock. The most common methods to evaluate AKI are creatinine clearance, plasma creatinine, blood urea nitrogen, or renal histology. However, currently, there are no precise methods to directly assess renal injury state noninvasively. Hyperpolarized 13C-pyruvate MRI enables noninvasive accurate quantification of the in vivo conversion of pyruvate to lactate, alanine, and bicarbonate. In the present study, we investigated the in situ alterations of metabolic conversion of pyruvate to lactate, alanine, and bicarbonate in a unilateral I/R-I rat model with 30 min and 60 min of ischemia followed by 24 h of reperfusion. The pyruvate conversion was unaltered compared with sham in the 30 min I/R-I group, while a significant reduced metabolic conversion was found in the postischemic kidney after 60 min of ischemia. This indicates that after 30 min of ischemia, the kidney maintains normal metabolic function in spite of decreased kidney function, whereas the postischemic kidney after 60 min of ischemia show a generally reduced metabolic enzyme activity concomitant with a reduced kidney function. We have confidence that these findings can have a high prognostic value in prediction of kidney injury and the outcome of renal injury.

[NEPHROPROTECTIVE PROPERTIES OF 5-HT3 RECEPTOR BLOCKER RU-63 IN EXPERIMENTAL ACUTE RENAL FAILURE UNDER HYPERGRAVITY CONDITIONS].

The effective diuretic dose of 5-HT3 receptor blocker RU-63 (1 mg/kg) was found in experiments on white rats. It is established that the diuretic and saluretic effects of compound RU-63 increase on the background of impact of the gravitational factor. Compound RU-63 (1 mg/kg, subcutaneously) administered daily under hypergravity conditions (3 g in the direction of centrifugal force toward the kidneys) in animals with model ischemic acute renal failure increased excretory function of kidneys, glomerular filtration rate, and creatininuresis (on average by 180%; p < 0.05), and decreased serum creatinine, urinary excretion of protein, lactate dehydrogenase, and g-glutamyl transferase (on average by 49%; p < 0.05) as compared to the untreated control. Under similar conditions, the diuretic hydrochlorothiazide (in a dose of 20 mg/kg, intragastric) produced a more pronounced creatininuretic action than that of RU-63 (by 358%; p < 0.05).

Differences in urinary proteins related to surgical margin status after radical prostatectomy.

Presented exploratory pilot study was aimed at evaluation of proteins present in urinary specimens collected from prostate cancer suffering subjects after radical prostatectomy, divided into two experimental cohorts: positive (n=15) and negative (n=15) surgical margins (PSM/NSM). The presence of PSM suggests inadequate cancer clearance and the possible need for additional treatment. Proper identification of these risk-patients is therefore of a paramount importance. Total protein profiles were firstly identified by using SDS-PAGE and compared by using partial least square discrimination analysis (PLS-DA), which revealed differences in molecular weights of 80-99 and 150-235 kDa between the experimental groups. For further identification of proteins, comparative proteomic technologies were employed. Two-dimensional gel electrophoresis with subsequent identification of protein spots by using MALDI-TOF mass fingerprinting revealed differential expression of proteins between NSM/PSM cohorts. Moreover, in PSM group, three uniquely identified proteins (cyclin-dependent kinase 6, galectin-3-binding protein and L-lactate dehydrogenase C chain) were found, which show tight connection with prostate cancer and presence of all of them was previously linked to certain aspects of prostate cancer. These proteins may be associated with the molecular mechanisms of prostate cancer development; hence, their identification may be helpful for the assessment of disease progression risk after radical prostatectomy, but also for possible early diagnosis.

Protective effects of N-acetylcysteine against hyperoxaluria induced mitochondrial dysfunction in male wistar rats.

The purpose of the present study was to evaluate the nephro-protective potential of N-acetylcysteine against hyperoxaluria-induced renal mitochondrial dysfunction in rats. Nine days dosing of 0.4 % ethylene glycol +1 % ammonium chloride, developed hyperoxaluria in male wistar rats which resulted in renal injury and dysfunction as supported by increased level of urinary lactate dehydrogenase, calcium, and decreased creatinine clearance. Mitochondrial oxidative strain in hyperoxaluric animals was evident by decreased levels of superoxide dismutase, glutathione peroxidase, glutathione reductase, reduced glutathione, and an increased lipid peroxidation. Declined activities of respiratory chain enzymes and tricarboxylic acid cycle enzymes showed mitochondrial dysfunction in hyperoxaluric animals. N-acetylcysteine (50 mg/kg, i.p.), by virtue of its -SH reviving power, was able to increase the glutathione levels and thus decrease the oxidative stress in renal mitochondria. Hence, mitochondrial damage is, evidently, an essential event in ethylene glycol-induced hyperoxaluria and N-acetylcysteine presented itself as a safe and effective remedy in combating nephrolithiasis.

[THE LEVEL OF LACTATE DEHYDROGENASE AS A MARKER OF RENAL DYSFUNCTION IN NEONATES WITH ASPHYXIA].

The article examines the possibility of determining the level of lactate dehydrogenase (LD) in biological fluids as a marker of renal dysfunction and energy supply in neonates with asphyxia. Investigation included 200 full-term newborns with disturbance kidney function: 100 infants who had severe asphyxia, and 100--with moderate asphyxia. LD activity was determined by kinetic spectrophotometric method. Determination of the activity of LD in the urine in the early neonatal period it is advisable to use as a non-invasive marker for the diagnosis of renal dysfunction in neonates with asphyxia. The content of LD in the blood serum can be used as one of the early markers of kidney damage in newborns with asphyxia.

Is urinary γ-glutamyl transpeptidase superior to urinary neutrophil gelatinase-associated lipocalin for early prediction of acute kidney injury after liver transplantation?

In this prospective study, we comparatively evaluated the accuracy of several biomarkers of acute kidney injury (AKI) on predicting its occurrence after liver transplantation (LT). The parameters evaluated were urinary tubular enzymes (γ-glutamyl transpeptidase [γGT], alkaline phosphatase, and urinary lactate dehydrogenase) and urinary neutrophil gelatinase-associated lipocalin. These parameters were evaluated both as isolated variables and divided by urinary creatinine. Samples were collected by the end of surgery (determination 1) and at 12 to 24 hours after surgery (determination 2). The study endpoint was the development of AKI. The study was performed over a 1-year period, and 61 of 77 patients were enrolled (main exclusion criteria were perioperative death, previous known renal failure, and insufficient data for analysis). Of these 61 patients, AKI was observed in 19 (group 1). The main relevant parameter to predict AKI was the absolute value of urinary γGT at determination 1 (area under the curve, 0.74; specificity, 72.5%; sensitivity, 70.3%; cutoff, 36 U/mL). Urinary neutrophil gelatinase-associated lipocalin was not as accurate; the best predicted value for this parameter was absolute value at D1 with an area under the curve of 0.5 (specificity, 84.2%; sensitivity, 35.7%; cutoff value, 44.6 ng/mL). We concluded that the absolute value of urinary γGT evaluated at the end of LT was the most accurate parameter to predict AKI in our cohort. Urinary enzyme levels must be taken into account in future analysis of this issue.

[Changes of the state of rat kidneys under guerin carcinoma development and use of cytostatics].

It was shown that development of the Guerin carcinoma and introduction of cisplatin led to the damage of the kidneys of rats that was confirmed by a relative increase of weight, proteinuria, change of gamma-glutamyl transpeptidase and lactate dehydrogenase activity in the urea and tissue homogenates of the kidneys, by a decrease of relative reabsorption and glomerular filtration. Introduction of nanoliposomal forms of the rhenium cluster compounds led to normalization of above mentioned diagnostic indexes and to reduction of the toxic cisplatin influence that was confirmed by biochemical and morphological investigations.

[Anti-lithogenic effect of meloxicam in experimental nephrolithiasis].

Experiments performed on 23 male rats, were divided into 2 groups. Animals in the control received group 1% solution of ethylene glycol (EG) as a drink during 6 weeks. In the test group, EG was also introduced for 6 weeks, and meloxicam was administered in a dose of 2.5 mg/kg from the 4th week. Every 7 days, daily urine was analyzed for the concentrations of oxalate, phosphate, and calcium and for the activity of urothelium injury marker enzymes includng lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and N-acetyl-beta-D-glucose aminidase (NAG). In addition, sections of the rats kidney were used to detect calcium deposits by histochemical Van Koss method. The treatment of experimental nephrolithiasis by meloxicame led to simplification of pathology, as indicated by a significant reduction in the urine oxalate and calcium concentrations and a pronounced decrease in the activity of all marker enzymes (LDH, GGT, NAG).This was confirmed by morphological studies, which detected very significant reduction in both number and size of calcium deposits.

[Experimental nephrolithiasis: nephroprotective effect of calcium antagonists].

Increasing intracellular calcium ion concentration in the cytoplasm is the starting point in the activation of cell death. Regulation of these pathological processes in various organs and tissues is possible using agents from the group of calcium antagonists. This study was aimed at assessing the level of urinary excretion of two enzymes, lactate dehydrogenase (LDH, EC 1.1.1.27) and y-glutamyltransferase (GGT, EC 2.3.2.2), calcium antagonists in an experimental model of nephrolithiasis and finding ways to pharmacological protection of the kidneys. It established that the use of calcium antagonists can reduce the excretion of LDH by 20% and the excretion of GGT by more than 40%.

The protective role of procyanidins and lycopene against mercuric chloride renal damage in rats.

OBJECTIVE: This study aims to investigate the protection of procyanidins and lycopene from the renal damage induced by mercuric chloride. METHODS: Rats were treated with either procyanidins or lycopene 2h before HgCl(2) subcutaneously injection, once daily treatment for 2 successive days. RESULTS: In comparison with HgCl(2) group, markers of renal function such as blood urea nitrogen in serum and urinary protein were decreased to (18.45±11.63) mmol/L and (15.93±9.36) mmol/L, (4.54±0.78) g/(g·Cr) and (4.40±1.12) g/(g·Cr). N-acetyl-beta-D-glucosaminidase, lactate dehydrogenase, alkaline phosphatase in urine were depressed to (125.49±11.68) U/(g·Cr), (103.73±21.79) U/(g·Cr), (101.99±12.28) U/(g·Cr), and (113.19±23.74) U/(g·Cr), (71.14±21.80) U/(g·Cr), (73.64±21.51) U/(g·Cr) in procyanidins and lycopene groups. Indicators of oxidative stress, for example, Glutathion was reduced to (45.58±9.89) µmol/(g·pro) and (45.33±5.90) µmol/(g·pro), and antioxidant enzymes such as superoxide dismutase, glutathione-peroxidase were enhanced to (43.07±10.97) U/(mg·pro) and (39.94±6.04) U/(mg·pro), (83.85±18.48) U/(mg·pro), and (85.62±12.68) U/(mg·pro). Malondialdehyde was lowered to (0.95±0.12) (µmol/g·pro) and (1.03±0.12) µmol/(g·pro) in procyanidins and lycopene groups. ROS generation was decreased by 27.63% and 16.40% and apoptosis was also decreased in procyanidins and lycopene groups respectively. Pathological changes were much better as well. CONCLUSION: Procyanidins and Lycopene play some protective role against mercury kidney damage.

The value of tubular enzymes for early detection of acute kidney injury after liver transplantation: an observational study.

Tubular enzymes (TE) are early markers of acute kidney injury (AKI), but their value for liver transplant (LT) recipients is unknown. We sought to evaluate the usefulness of TE to predict AKI after LT. We enrolled Thirty-nine adult patients without AKI who had been admitted to the Intensive Care Unit (ICU). AKI was diagnosed according to the Acute Kidney Injury Network criteria. Of these patients, 23 had received orthotopic LT and 16 controls had been admitted for other conditions. Urinary lactate dehydrogenase (LDH), alkaline phosphatase (AF) and γ-glutamyl transpeptidase (γ-GT) measured on days 1 and 3 of the ICU stay were normalized to urinary creatinine concentrations. AKI was diagnosed in 14 patients: 8 in the LT group and 6 in the control group. In the LT group, on the first day of the patients' stay in the ICU, urinary LDH (P = .032), AF (P = .022), and γ-GT (P = .002) were significantly higher among those who developed AKI; these elevations preceded those of serum creatinine. In forward receiver-operating characteristic (ROC) plot analysis, the areas under the ROC curves were 0.8, 0.86, and 0.92 for LDH, AF, and γ-GT, respectively. We concluded that TE determined early after LT are a helpful predictors of AKI.

Evaluation of the usefulness of urinary biomarkers for nephrotoxicity in rats.

Since nephrotoxicity affects the development of drug candidates, it is important to detect their toxicity at an early stage of drug development. In this study, we measured twelve urinary nephrotoxic biomarkers [total protein, albumin, kidney injury molecule-1 (KIM-1), clusterin, beta2-microglobulin, cystatin-c, alpha-glutathione S-transferase, mu-glutathione S-transferase, N-acetyl-beta-d-glucosaminidase, lactate dehydrogenase (LDH), aspartate aminotransferase and neutrophil gelatinase-associated lipocalin (NGAL)] and two conventional blood nephrotoxic biomarkers (creatinine and blood urea nitrogen) in rat models treated intravenously with puromycin aminonucleoside (PAN) or cisplatin (CDDP), which are known to induce glomerular injury or proximal tubular injury, respectively, and evaluated their usefulness by receiver operating characteristic analysis. In the PAN-treated rats, urinary albumin and (NGAL) were dramatically increased, which were thought to be caused by the dysfunction of proximal tubule in addition to glomerular injury. Conversely, based on its early and time-dependent increase, its large magnitude of alteration and its high accuracy and sensitivity of detection, (KIM-1) in urine appeared to be the best biomarker for detection of CDDP-induced proximal tubular injury. Moreover, (LDH) was considered useful for broad detection of damaged nephrons, because of its broad distribution along the nephron. Therefore, combinatorial measurement of these biomarkers may be a powerful tool for highly effective screening of nephrotoxicity.

Physical and biochemical characteristics of biological fluids in rats with modeled thermal injury.

Lactate dehydrogenase activity, crystallogenic and initiator characteristics of biological substrates were evaluated by enzymological and crystalloscopic analysis of rat serum and urine. Changes in these characteristics of biological media in combined thermal injury were shown. This approach is effective for evaluation of the metabolic status in rats with experimental burn disease.

Expression of kidney injury molecule-1 (Kim-1) in relation to necrosis and apoptosis during the early stages of Cd-induced proximal tubule injury.

Cadmium (Cd) is a nephrotoxic industrial and environmental pollutant that causes a generalized dysfunction of the proximal tubule. Kim-1 is a transmembrane glycoprotein that is normally not detectable in non-injured kidney, but is up-regulated and shed into the urine during the early stages of Cd-induced proximal tubule injury. The objective of the present study was to examine the relationship between the Cd-induced increase in Kim-1 expression and the onset of necrotic and apoptotic cell death in the proximal tubule. Adult male Sprague-Dawley rats were treated with 0.6 mg (5.36 micromol) Cd/kg, subcutaneously, 5 days per week for up to 12 weeks. Urine samples were analyzed for levels of Kim-1 and the enzymatic markers of cell death, lactate dehydrogenase (LDH) and alpha-glutathione-S-transferase (alpha-GST). In addition, necrotic cells were specifically labeled by perfusing the kidneys in situ with ethidium homodimer using a procedure that has been recently developed and validated in the Prozialeck laboratory. Cryosections of the kidneys were also processed for the immunofluorescent visualization of Kim-1 and the identification of apoptotic cells by TUNEL labeling. Results showed that significant levels of Kim-1 began to appear in the urine after 6 weeks of Cd treatment, whereas the levels of total protein, alpha-GST and LDH were not increased until 8-12 weeks. Results of immunofluorescence labeling studies showed that after 6 weeks and 12 weeks, Kim-1 was expressed in the epithelial cells of the proximal tubule, but that there was no increase in the number of necrotic cells, and only a modest increase in the number of apoptotic cells at 12 weeks. These results indicate that the Cd-induced increase in Kim-1 expression occurs before the onset of necrosis and at a point where there is only a modest level of apoptosis in the proximal tubule.

Shockwave lithotripsy and protective role of inosine: early and late evaluation in an experimental model.

PURPOSE: Extracorporeal shockwave lithotripsy (SWL) is one of the most common treatments for urinary stones. Despite technological improvements, it may cause side effects varying from minor reversible microscopic damage to severe large renal hematomas. The aim of our experimental study is to assess the efficacy of inosine in avoidance of acute renal damage after SWL. MATERIALS AND METHODS: We used 25 Wistar rats that had previously had left nephrectomy. The rats were divided into three groups: group A consisted of 10 rats undergoing renal SWL; group B consisted of 10 rats that received adjunctive treatment with IP injection of inosine 40 minutes before SWL; and group C consisted of 5 rats that served as controls. N-acetylglucosaminidase (NAG) and lactate dehydrogenase (LDH) concentrations were evaluated 24 hours before and 24 hours after SWL. All the rats were subsequently sacrificed (4 rats in group A and 4 in group B at 48 hours post-SWL, and the remaining rats were sacrificed 30 days post-SWL). Renal tissue was submitted to histologic and electron microscopic examination to assess early and late alterations. RESULTS: NAG and LDH values were significantly increased after SWL in group A (P<0.001), while no significant NAG and LDH differences were detected in group B (P<0.16). Early histologic examination revealed a considerable amount of cellular degeneration in group A with ultrastructural vacuolization and disruption of lysosomal membranes; the tubular features and cellular structures appeared to be well preserved in group B. No late histologic alterations were evident in any of the specimens. CONCLUSIONS: Inosine is helpful and protective in the prevention of early microscopic damage to renal parenchyma due to SWL.

[Specific features of lactate dehydrogenase activity in blood and urine of males and females with renal carcinoma].

We studied activity of lactate dehydrogenase (LDG) in blood serum and urine of males and females with renal carcinoma as well as in healthy controls in various age groups for specification of LDG role for early diagnosis of the disease. We examined 101 patients with renal carcinoma (males 65.3%, females 34.7%, age 20-80 years, histological verification 98%) and 119 controls matched by gender, age and residence. LDG activity was determined by kinetic UV-test with a special kit. Statistic significance of the results was estimated using such indices as relative risk, confidence interval, two-sample t-test with various variances. Blood LDG was higher more often in 50--59 year old males and females, but differences with the control were not significant. Statistically significant elevation of LDG level in urine in males and insignificant one in females were observed. We believe that LDG activity test as an additional test for early diagnosis of renal carcinoma is justified both in males and females.

Lysosomal enzymuria is a feature of hereditary Fanconi syndrome and is related to elevated CI-mannose-6-P-receptor excretion.

BACKGROUND: Lysosomal enzymuria is usually considered to be a non-specific marker of renal injury, but little is known about lysosomal enzyme excretion in renal proximal tubular cell disorders such as the renal Fanconi syndrome (FS). We examined excretion of two lysosomal enzymes and the cation-independent mannose-6-phosphate receptor (CI-MPR) in patients with inherited FS. METHODS: The lysosomal enzyme cathepsin D was measured by ELISA and isolated by pepstatin-agarose affinity chromatography; N-acetyl-beta-d-glucosaminidase (NAG) was assayed colorimetrically, as was the cytosolic enzyme lactate dehydrogenase (LDH). Cathepsin D, procathepsin D and CI-MPR were also detected by western blotting. No patient had a serum creatinine concentration >170 micromol/L. Soluble CI-MPR, isolated from fetal calf serum and bound to agarose, was used to probe cathepsin D for mannose-6-phosphate (M6P). RESULTS: Increased excretion of cathepsin D (mean = 44-fold) and NAG (mean = 12-fold) was found in FS patients: Dent's disease (n = 5), cystinosis (n = 4), Lowe syndrome (n = 3) and 'autosomal dominant idiopathic FS' (ADIF) (n = 2). Increased cathepsin D excretion was confirmed by western blotting; excretion of procathepsin D and LDH was not increased. When compared with control subjects, CI-MPR excretion was also increased in FS (n = 6). Thus, significantly increased excretion of lysosomal enzymes and CI-MPR was found in all cases of FS examined. Cathepsin D binding to CI-MPR-agarose was inhibited by M6P. CONCLUSIONS: We conclude that underlying gene defects in FS may disrupt normal membrane trafficking of CI-MPR, leading to mistrafficking of lysosomal enzymes via a default pathway from the Golgi to the apical surface of proximal tubule cells rather than to lysosomes. Lysosomal enzymes are then secreted into the tubular fluid and excreted in the urine. This contrasts with the widely held view that cell necrosis is the cause of lysosomal enzymuria in renal disease. Moreover, cathepsin D in FS urine is M6P-tagged.