Rapid screening and determination of pesticides on lemon surfaces using the paper-spray mass spectrometry integrated via thermal desorption probe.

This paper presents a novel thermal desorption probe integrated with the corona-discharged assisted paper-spray mass spectrometry (PS-MS) for rapid detecting the residual pesticides on fruit surfaces. Pesticide detection can be simply achieved by scratching the fruit surface and then placed in front of the inlet of the MS for target pesticides screening. A novel ionization method comprising the electrospray ionization and the corona discharged is generated on the paper tip to simultaneously ionize the pesticide of high and low polarities for MS detection. Six pesticides composed of polar acetamiprid, azoxystobin, pyridaben and low polar chlorfenapyr, pyriproxyden, λ-cyhalothrin are successfully detected in seconds. The results are also validated with the LC-MS/MS and GC-MS/MS spectra performed via the standard protocols by a certificated laboratory of Eurofins Taiwan. The developed method provides a rapid, simple yet efficient way for screening residual pesticides on fruits.

A novel preventive mechanism of gentamicin-induced nephrotoxicity by atorvastatin.

Atorvastatin (ATO) inhibits the synthesis of nonsteroidal isoprenoid compounds and possesses a pleiotropic effect. However, the detailed mechanism of ATO in preventing gentamicin (GM)-induced renal injury remains obscure. Although underlying multifaceted mechanisms involving GM-induced nephrotoxicity were well known, further work on elucidating the essential mechanism was needed. Using a fluorogenic derivatization-liquid chromatography tandem mass spectrometry proteomic method (FD-LC-MS/MS method), we investigated the effects and mechanisms of ATO treatment on GM-induced nephrotoxicity in rats. Consequently, 49 differentially expressed proteins were identified. The most significant mechanisms of nephrotoxicity caused by GM were mitochondrial dysfunction, fatty acid metabolism and oxidative stress. Their upstream regulator was found to be PPARα. The proteins involved in GM nephrotoxicity were sodium-hydrogen exchanger regulatory factor (SLC9A3R1), cathepsin V (CTSV), macrophage migration inhibitory factor (MIF) and RhoGDP dissociation inhibitor alpha (ARHGDIA). After ATO intervention, we observed a reversed enrichment pattern of their expression, especially in CTSV and SLC9A3R1 (P-value<0.05). We predicted that ATO may improve abnormal phospholipid metabolism and phospholipidosis caused by GM and also alleviate cell volume homeostasis and reverse the interference of GM with the transporter. Furthermore, proteomic results also provided clues as to GM-induced nephrotoxicity biomarkers such as CTSV and transthyretin.

Inhibitory effect of berberine on interleukin-2 secretion from PHA-treated lymphocytic Jurkat cells.

Berberine is an isoquinoline alkaloid isolated from herb plants, such as Cortex phellodendri (Huangbai) and Rhizoma coptidis (Huanglian). Huanglian and Huangbai have been used as "heat-removing" agents. In addition, berberine has been reported to exert anti-inflammatory effect both in vivo and in vitro, where mitogen-activated protein kinase (MAPK) and cyclooxygenase-2 (COX-2) expressions are critically implicated. We herein tested the hypothesis that berberine exerts an anti-inflammatory effect through MAPK and COX-2 signaling pathway in T-cell acute lymphoblastic leukemia (T-ALL). In Jurkat cells, we found that PHA exposure caused elevation on interleukin-2 (IL-2) production in a time-dependent manner. PHA-stimulated reactions were steeply suppressed by berberine, such as IL-2 mRNA expression and protein secretion. However, berberine did not exert any cytotoxic effect at doses of 40 µg/ml. In addition, the possible molecular mechanism of anti-inflammation effect of berberine could be the inhibition of PHA-evoked phosphorylation of p38, since c-Jun N-terminal kinases (JNK) and extracellular signal-regulated kinase (ERK) expressions did not alter. Consistent with above results, berberine inhibition on PHA-induced IL-2 secretion could be reversed by treatment of SB203580, a specific inhibitor of p38-MAPK. Interestingly, upregulation of PHA-induced COX-2 expression was also observed following berberine treatment of Jurkat cells. Furthermore, flow cytometry analysis showed berberine-induced cell cycle arrest at G1 phase after PHA stimulation and decreased percentage of G2/M phase. In conclusion, our study demonstrated that the anti-inflammatory effect of berberine largely potentially results from its ability to attenuate p38 MAPK expression, and does not exclude a positive action of berberine on cell cycle arrest. These results provide an innovative medicine strategy to against or treat T-ALL patients.

Electrothermal bipolar vessel sealing device (LigaSure™) versus conventional diathermy in laparoscopic myomectomy: A propensity-matched analysis.

The purpose of this study was to compare the safety and efficacy of an electrothermal bipolar vessel sealing device (LigaSure™) and traditional electrical cauterization in laparoscopic myomectomy (LM). A total of 756 patients with symptomatic uterine myomas who underwent LM were reviewed retrospectively. A total of 225 cases of LM using LigaSure™ (LML group) were compared with a control group treated with traditional electrical cauterization (LME group) under propensity-matched analysis. Outcome measures for both groups were compared, such as operative time, blood loss (BL), complications, need for blood transfusion, hospital expenses, and hospital stay. Six subgroups were divided according to main myoma size and energy source. No cases required switching to abdominal myomectomy. The number of myomas removed, BL, need for blood transfusion, and complications were not significantly different, whereas hospital stay was longer in the LME group than in the LML group and total hospital expenses were higher in the LML group (p < 0.001). The overall operation duration was significantly longer in the LML group but was not significantly different for main myoma >10 cm (LML vs LME, 121.58 ± 41.77 vs 121.69 ± 44.95, p = 0.99); this likely reflects the operative efficiency on using LigaSure™ to manage large tumors. Significant linear correlations between myoma weight and operative time and BL were seen in both groups. Conventional diathermy is more effective for small-to-medium myomas. Use of the LigaSure™ was efficient for myomas >10 cm.

Comparison of three different hemostatic devices in laparoscopic myomectomy.

BACKGROUND: To compare conventional electrosurgery, LigaSure (Valleylab, Boulder, CO), and Harmonic scalpel (Ethicon Endosurgery, Cincinnati, OH) in terms of perioperative and postoperative outcomes during laparoscopic myomectomy (LM). METHODS: We retrospectively studied 817 women with symptomatic fibroids who underwent LM between January 1997 and September 2015. Three different instruments were used separately during surgery. The number and weight of removed fibroids, blood loss, operative time, postoperative decrease in the hemoglobin level, and length of hospital stay were measured for statistical analysis. RESULTS: No significant increase in complications was found in the three groups. Patients in the LigaSure and Harmonic scalpel groups had more numbers of removed fibroids, heavier fibroids removed, and higher rate of pretreatment with GnRH agonist (p < 0.001). These patients also had higher amount of intraoperative bleeding (p = 0.003) and longer operative time (p < 0.001) than those in the conventional electrosurgery group. However, no worse postoperative clinical outcome but shorter length of hospital stay was found in the LigaSure and Harmonic scalpel groups (2.1 ± 0.6, 2.0 ± 0.4 vs 2.5 ± 0.8 days, p < 0.001). CONCLUSION: The use of all three devices is feasible in LM. LigaSure and Harmonic scalpel can reduce the length of hospital stay without worse surgical outcomes.

Elevated levels of liver methylglyoxal and d-lactate in early-stage hepatitis in rats.

Methylglyoxal (MGO) is highly cytotoxic and its levels are elevated in diabetes, nephropathy and atherosclerosis. However, it has never been studied in liver disease. For this reason, we aimed to assess the levels of MGO and its metabolite d-lactate in an early hepatitis model. Wistar rats were administered CCl4 (0.75 mL/kg, i.p.) to induce hepatitis. In either CCl4 -treated or untreated rats, alanine transaminase and aspartate transaminase levels did not change over the course of the study, indicating that significant liver damage did not occur following CCl4 treatment. However, the levels of MGO and d-lactate were higher in the livers of CCl4 -treated animals than in untreated animals (MGO: 128.2 ± 18.8 and 248.1 ± 64.9 µg/g protein, p < 0.01; d-lactate: 0.860 ± 0.040 and 1.293 ± 0.078 µmol/g protein, respectively p < 0.01). Furthermore, in untreated and treated animals, serum d-lactate levels were 57.65 ± 2.59 and 92.16 ± 16.69 µm and urine d-lactate levels were 1.060 ± 0.007 and 1.555 ± 0.366 µmol/mg UCr, respectively (p < 0.01). These data show that in this model of early-stage liver damage, the levels of MGO and its metabolite d-lactate are elevated and that d-lactate could be useful as a reference marker for the early stage of hepatitis.

Corrigendum to "Chitosan Prevents Gentamicin-Induced Nephrotoxicity via a Carbonyl Stress-Dependent Pathway".

[This corrects the article DOI: 10.1155/2015/675714.].

Transvaginal endoscopic surgery-assisted versus conventional laparoscopic adnexectomy (TVEA vs. CLA): A propensity-matched study and literature review.

OBJECTIVE: Natural orifice transluminal endoscopic surgery (NOTES) may be useful in gynecologic endoscopic surgery. This study evaluated the efficacy, safety, and perioperative outcomes of combined NOTES and vaginal approach, transvaginal endoscopic surgery-assisted adnexectomy (TVEA), for the surgical treatment of presumed benign ovarian tumors. MATERIALS AND METHODS: Records were reviewed for 33 consecutive TVEA procedures performed between May 2011 and March 2014. Patient age, body mass index, parity, mass size, and mass bilaterality were used to select comparable patients who had undergone conventional laparoscopic adnexectomy (CLA). RESULTS: A total of 236 patients were included in this study (203 CLAs and 33 TVEAs). No cases switched to abdominal laparotomy. Operating time and length of postoperative stay were significantly longer in the CLA group than in the TVEA group, while total hospital charges were higher in the TVEA group (p < 0.001). There was no difference in febrile morbidity between the two groups; while the estimated blood loss was higher in the TVEA group, the EBL was <30 mL in both groups. CONCLUSION: TVEA can be safely performed for benign and large ovarian tumors. In addition, TVEA offers superior operative efficiency compared to CLA.

The use of fibrin sealant (Tisseel) in laparoscopic excision of ovarian endometrioma.

OBJECTIVE: To evaluate the use of Tisseel, a 2-component fibrin sealant agent for the control of minor bleeding and repair of the ovarian defect at the end of laparoscopic cystectomy (LC) of endometriomas. MATERIALS AND METHODS: From January 2011 to December 2015, an observational study of all patients who underwent LC of endometrioma using Tisseel (group A) was performed. The demographic and operative data, including age, body mass index, operative indications, operative time, estimated blood loss, complications, and postoperative hospital stay duration were recorded. A contemporary cohort of patients, who underwent LC of endometrioma without Tisseel (group B) was also retrospectively compared. RESULTS: A total of 274 patients were recruited in this study (53 LCs with Tisseel and 221 LCs without Tisseel, respectively). Complete hemostasis was achieved in all patients. The mean size of main mass was significantly larger in the group A than in the group B (7.8 ± 2.4 cm vs. 7.0 ± 2.3 cm, p = 0.033) but the mean operating time, operative blood loss, febrile morbidity, and length of hospitalization were not significantly different between the two groups. CONCLUSION: This preliminary series demonstrated the use of Tisseel in LC of endometriomas without any bipolar coagulation and/or suturing of ovarian tissue is clinically safe and feasible.

Accumulation of methylglyoxal and d-lactate in Pb-induced nephrotoxicity in rats.

Lead (Pb) is an environmental pollutant associated with several diseases, such as nephrotoxicity. Methylglyoxal (MG) is a reactive dicarbonyl compound formed during glycolysis and reported to increase in kidney damage. Metformin is used as an MG scavenger in the clinic. In this study, we investigated the mechanism of Pb-induced renal injury and the effect of metformin on Pb-induced nephrotoxicity. Eighteen Wistar rats were randomly divided into three groups: control, Pb, and Pb + metformin groups. Pb (250 ppm) was administered in drinking water, and 50 mg/kg of metformin was co-administered orally. After 28 days, the levels of MG and its metabolite d-lactate in urine, serum and renal tissues were examined. The elevation of renal MG (56.86 ± 17.47 vs 36.40 ± 5.69, p < 0.01) and urinary d-lactate (0.68 ± 0.28 vs 0.32 ± 0.13, p < 0.01) was observed in Pb-exposed rats compared with those in control rats. After co-treatment with metformin, these phenomena were attenuated. In the present study, it was demonstrated for the first time that urinary d-lactate might serve as the candidate marker for Pb-induced nephrotoxicity in the clinic, and metformin might be a new therapeutic candidate for Pb poisoning.

Laminin Receptor in Shrimp Is a Cellular Attachment Receptor for White Spot Syndrome Virus.

White spot syndrome virus (WSSV, genus Whispovirus, family Nimaviridae) is causing huge economic losses in global shrimp farming, but there is no effective control. Shrimp cell laminin receptor (Lamr) may have a role in WSSV infection. The objective was to characterize interactions between Penaeus monodon Lamr (PmLamr) and WSSV structural proteins. In this study, PmLamr interacted with nine WSSV structural proteins (based on yeast two-hybrid screening), of which one (VP31) was characterized. Protein pull-down assay confirmed the interaction between PmLamr and VP31; the latter was an envelope protein exposed outside the WSSV virion (based on membrane topology assays). Furthermore, similar to mammalian Lamr, there were two major protein bands in shrimp cells. Cellular localization assay demonstrated VP31 co-localized with PmLamr on transfected cells. Enzyme-link immunosorbent assay (ELISA) and competitive ELISA demonstrated binding of VP31 on PmLamr was dose-dependent; however, addition of WSSV virion competed for binding affinity. Furthermore, based on an in vivo neutralization assay, both VP31 and PmLamr delayed mortality in shrimp challenged with WSSV. We concluded Lamr was an important receptor for WSSV infection and the viral envelope protein VP31 may have a role in host cell recognition and binding. These data contributed to elucidating pathogenesis of WSSV infection and may help in controlling this disease.

Low-molecular-weight chitosan scavenges methylglyoxal and N (ε)-(carboxyethyl)lysine, the major factors contributing to the pathogenesis of nephropathy.

Methylglyoxal (MG) can cause protein glycation, resulting in cell damage and dysfunction. Accumulation of MG and its downstream metabolite N (ε)-(carboxyethyl)lysine (CEL) has been identified in several variations of nephropathy, including diabetic, hypertensive, and gentamicin-induced nephropathies. In this study, we investigated the effects of low-molecular-weight chitosan (lmw-chitosan) on MG-induced carbonyl stress in aristolochic acid-induced nephropathy. We used a buffer to investigate whether MG could be scavenged by lmw-chitosan in vitro. In addition, we also used a mouse model of aristolochic acid-induced nephropathy, which exhibits 12-fold greater accumulation of MG in the kidneys than that found in control animals, to examine whether lmw-chitosan could decrease MG levels in vivo. Examination of the binding of lmw-chitosan with MG in vitro demonstrated that the concentration of lmw-chitosan necessary to achieve 50% inhibition was 4.60 µg mL(-1). Treatment with lmw-chitosan (500 mg kg(-1) day(-1) orally) for 14 days significantly decreased renal MG accumulation from 212.86 ± 24.34 to 86.15 ± 33.79 µg g(-1) protein (p < 0.05) and CEL levels from 4.60 ± 0.27 to 2.84 ± 0.28 µmol µg(-1) protein (p < 0.05) in the aristolochic acid-induced nephropathy model. These data suggest that lmw-chitosan might represent a novel treatment modality for MG-related diseases such as nephropathy.

Elevated urinary D-lactate levels in patients with diabetes and microalbuminuria.

Diabetic nephropathy (DN) has become the major cause of end-stage renal disease. Early detection of disease risk, to enable intervention before advanced renal damage occurs, is an important goal. Microalbuminuria has been used to monitor renal damage in clinical settings for years. In this study, we divided patients with diabetes into different groups based on their microalbumin values to elucidate the relationship between urinary D-lactate and corresponding microalbumin values. Group DM1 comprised of patients with an albumin-to-creatinine ratio (ACR) of less than 30 µg albumin/mg creatinine (normal range); Group DM2 comprised of patients with an ACR of 30-299 µg albumin/mg creatinine (microalbuminuria); and Group DM3 comprised of patients with an ACR of ≥300 µg albumin/mg creatinine (macroalbuminuria). The urinary D-lactate concentration of patients with diabetes was determined by pre-column fluorescence derivatization with 4-nitro-7-piperazino-2,1,3-benzoxadiazole (NBD-PZ), and the accuracy (recovery) and precision (relative standard deviation; RSD) were validated. The measured values showed an accuracy that was in the acceptable range (91.59-112.96%), with an RSD in the range of 3.13-13.21%. The urinary D-lactate levels of the 3 diabetic groups (groups DM1, DM2, and DM3) were significantly higher than those of healthy subjects (78.31 ± 22.13, 92.47 ± 21.98, and 47.29 ± 17.51 vs. 6.28 ± 2.39 nmol/mg creatinine, respectively; p<0.05), with urinary D-lactate levels in the DM2 group being the highest. This modified fluorescence-based, high-performance liquid chromatography method to quantify D-lactate concentrations in the urine of patients with diabetes was established. Also, measuring the new risk marker identified in this study (D-lactate) in combination with microalbumin may facilitate the prevention of DN.

Chitosan Prevents Gentamicin-Induced Nephrotoxicity via a Carbonyl Stress-Dependent Pathway.

Aminoglycosides are widely used to treat infections; however, their applications are limited by nephrotoxicity. With the increase of antibiotic resistance, the use of aminoglycosides is inevitable. Low-molecular-weight chitosan (LMWC) has shown renal protective effects in dialysis patients. However, no study has evaluated LMWC for preventing aminoglycoside-induced nephrotoxicity or determined the mechanisms underlying the renal protective effects. In this study, LMWC (165 or 825 mg/kg/day) or metformin (100 mg/kg/day) was orally administered for 13 days to rats with nephropathy induced by gentamicin (GM), a kind of aminoglycoside (150 mg/kg/day i.p. for 6 days). Both LMCW doses improved renal function. Serum creatinine levels improved in rats treated with 165 and 825 mg/kg/day LMWC (from 2.14 ± 0.74 mg/dL to 1.26 ± 0.46 mg/dL and 0.69 ± 0.12 mg/dL, resp., P < 0.05). Blood urea nitrogen levels were also improved in these rats (from 73.73 ± 21.13 mg/dL to 58.70 ± 22.71 mg/dL and 28.82 ± 3.84 mg/dL, resp., P < 0.05). Additionally, renal tissue morphology improved after LMWC treatment, and accumulation of renal methylglyoxal, a damage factor associated with carbonyl stress, was reversed. These results show that LMWC prevents GM-induced renal toxicity via a carbonyl stress-dependent pathway.

Increased renal semicarbazide-sensitive amine oxidase activity and methylglyoxal levels in aristolochic acid-induced nephrotoxicity.

AIMS: Aristolochic acid (AA) nephrotoxicity is related to accumulation of methylglyoxal (MGO) and N(ε)-(carboxymethyl)lysine (CML) in the mouse kidney. We studied the activity of renal semicarbazide-sensitive amine oxidase (SSAO), a key enzyme involved in MGO generation, in AA-treated mice, and investigated nephroprotective effects produced by metformin, a MGO scavenger. METHODS: Mice were orally administered water or metformin for 15 days (12 or 24 mg kg(-1)day(-1)), and injected AA (5mgkg(-1)day(-1)) intraperitoneally for 8 days starting on day 8. Renal function was studied, and histopathological examination, determination of renal SSAO activity, and measurement of MGO levels were performed. KEY FINDINGS: Compared to control mice, AA-injected mice showed significant renal damage and approximately 2.7-fold greater renal SSAO activity (p<0.05). Further, compared to control treatment, administration of 12 mg/kg metformin inhibited formation of renal lesions, and significantly decreased renal MGO levels (37.33 ± 9.78 vs. 5.89 ± 2.64 µg/mg of protein, respectively, p<0.01). In the AA-treated mice, metformin also inhibited the accumulation of CML in renal tubules, but did not affect SSAO activity. SIGNIFICANCE: This study is the first to show elevated renal SSAO activity in AA-treated mice, which could be involved in MGO accumulation. Moreover, MGO scavenging by metformin reduces AA nephrotoxicity. These findings suggest that reducing MGO accumulation produces nephroprotection, revealing new therapeutic strategies for the management. SSAO is a key enzyme involved in MGO generation, and consequently, inhibition of renal SSAO activity is worth investigating in AA nephrotoxicity and other renal pathologies further.

Lactoferrin dampens high-fructose corn syrup-induced hepatic manifestations of the metabolic syndrome in a murine model.

Hepatic manifestations of the metabolic syndrome are related obesity, type 2 diabetes/insulin resistance and non-alcoholic fatty liver disease. Here we investigated how the anti-inflammatory properties of lactoferrin can protect against the onset of hepatic manifestations of the metabolic syndrome by using a murine model administered with high-fructose corn syrup. Our results show that a high-fructose diet stimulates intestinal bacterial overgrowth and increases intestinal permeability, leading to the introduction of endotoxin into blood circulation and liver. Immunohistochemical staining of Toll-like receptor-4 and thymic stromal lymphopoietin indicated that lactoferrin can modulate lipopolysaccharide-mediated inflammatory cascade. The important regulatory roles are played by adipokines including interleukin-1ß, interleukin-6, tumor necrosis factor-α, monocyte chemotactic protein-1, and adiponectin, ultimately reducing hepatitis and decreasing serum alanine aminotransferase release. These beneficial effects of lactoferrin related to the downregulation of the lipopolysaccharide-induced inflammatory cascade in the liver. Furthermore, lactoferrin reduced serum and hepatic triglycerides to prevent lipid accumulation in the liver, and reduced lipid peroxidation, resulting in 4-hydroxynonenal accumulation. Lactoferrin reduced oral glucose tolerance test and homeostasis model assessment-insulin resistance. Lactoferrin administration thus significantly lowered liver weight, resulting from a decrease in the triglyceride and cholesterol synthesis that activates hepatic steatosis. Taken together, these results suggest that lactoferrin protected against high-fructose corn syrup induced hepatic manifestations of the metabolic syndrome.

Urinary d-lactate levels reflect renal function in aristolochic acid-induced nephropathy in mice.

Urinary d-lactate is highly correlated to diabetic nephropathy - a progressive kidney disease in renal glomeruli. In this study, we used a C3H/3e mouse model to investigate the relationship between urinary d-lactate and aristolochic acid nephropathy where the glomerular structure is not affected. The nephropathy was induced using intravenous injections of aristolochic acid at a dosage of 10 mg/kg per day for 5 days and was characterized biochemically and histologically. The urinary excretions of proteins, N-acetyl-ß-d-glucosaminidase and serum creatinine were determined and connected to histological conventional findings. Urinary d-lactate was analyzed using column-switching high-performance liquid chromatography with fluorescence detection. The results showed a remarkable increase of urinary markers, including of urinary proteins and N-acetyl-ß-d-glucosaminidase, and the histological examination confirmed a diagnosis of acute tubule necrosis. The ratio of d-lactate to creatinine in the urine of aristolochic acid-treated mice was approximately 36 times greater than that of the mice in the control group (p < 0.05). The ratios for the two groups of mice were 311.00 ± 71.70 and 8.60 ± 1.80 µmol/mmol creatinine, respectively. These data confirm in vivo that urinary d-lactate reflects renal injury conditions in aristolochic acid-treated mice and may be a marker for the assessment of nephropathy.

Gentamicin caused renal injury deeply related to methylglyoxal and N(ɛ)-(carboxyethyl)lysine (CEL).

In this study, we investigated the role of carbonyl stress in gentamicin (GM)-induced renal injury in rats. Carbonyl stress is represented by methylglyoxal (MGO) and its downstream advanced glycation end products, such as N(ɛ)-(carboxyethyl)lysine (CEL). GM (150mg/kg/day, i.p.) administration for 6 days significantly increased blood urea nitrogen (BUN) levels from 24.06±0.55 to 85.04±21.31mg/dL and decreased creatinine clearance rate (Ccr) from 10.68±0.76 to 2.53±1.11ml/min/kg B.W.; biopsy showed tubular injury. The kidney levels of MGO and CEL increased significantly from 9.56±1.94 to 79.13±17.96µg/g of protein and from 0.03±0.00 to 0.06±0.00µmol/µg of protein, respectively. Therefore, MGO and CEL appeared to be associated with GM-induced renal damage. Co-administration of metformin (50 or 100mg/kg/day) and GM for 13 days effectively reversed GM-induced renal damage. The kidney levels of MGO and CEL decreased significantly from 24.95±7.74 to 22.98±17.74µg/g of protein and from 0.04±0.01 to 0.03±0.01µmol/µg of protein (both vs. the GM group), respectively. The identification of this new pathway may help prevent GM-induced nephrotoxicity.

Proteome analysis of altered proteins in streptozotocin-induced diabetic rat kidney using the fluorogenic derivatization-liquid chromatography-tandem mass spectrometry method.

To find new molecular markers for early diagnosis of diabetic nephropathy, we applied fluorogenic derivatization-liquid chromatography-tandem mass spectrometry to identify the differentially expressed proteins in the kidney of control and streptozotocin-induced diabetic rats. The Sprague-Dawley rats were injected with the sodium citrate buffer or streptozotocin and then killed after 1, 4, 12 and 24 weeks. The results showed that seven proteins were significantly changed after 1 week of injection. Only one protein had significantly changed after 4 weeks of injection. However, after 12 weeks of injection, the number of altered proteins rose to 10. After 24 weeks of injection, 18 proteins had altered significantly. Five common proteins were significantly altered at week 12 and 24 after injection, respectively. Importantly, these proteins appeared prior to microalbuminuria and may serve as new biomarkers that are able to improve early detection of and new drug development for diabetic-related nephropathy.