1.The effect of GMDTC on attenuating cisplatin-induced toxicity in the treatment of tumor-bearing rats
Xin DUAN ; Wei HU ; Zhiyong ZHONG ; Xiaojiang TANG
China Occupational Medicine 2025;52(2):121-128
Objective To investigate the protective effect of sodium (s)-2-(dithiocarboxylato((2R,3R,4R,5R,6R)-2,3,4,5,6-pentahydroxyhexyl) amino)-4-(methylthio) butanoate (GMDTC) against cisplatin-induced toxicity during antitumor treatment. Methods Specific pathogen-free female SD rats were inoculated with LLC-WRC-256 tumor cells to establish tumor-bearing models, which were randomly divided into the model control group, cisplatin control group, and low-, medium-, and high-dose GMDTC groups, with 10 rats in each group. Another negative control group with 10 rats was included. Rats in the cisplatin control group and the three GMDTC dose groups were injected intravenously with cisplatin at a dose of 5 mg/kg body mass for one time. After 2.0 hours, rats in the three GMDTC dose groups were injected intravenously with GMDTC at doses of 27, 54, and 108 mg/kg body mass, once per day for five consecutive days. Tumor volume, platinum levels in biological samples (whole blood, urine, kidney, and tumor tissue), serum creatinine (Cr) and urea nitrogen (BUN) levels were measured at different time points. The tumor mass was measured, the pathological changes of renal tissue were observed, and the complete blood count was tested. Results The dilation of renal tubules, cell necrosis and shedding, and the formation of renal tubule patterns in the kidneys of rats in the medium- and high-dose GMDTC groups were significantly reduced compared with those in the cisplatin control group. The tumor volume of rats in the cisplatin control group and the three GMDTC dose groups decreased on the 3rd, 5th and 7th days after cisplatin administration, and the tumor weight decreased on the 7th days compared with the model control group (all P<0.05). However, there was no significant difference in the above indexes among the four groups (all P>0.05). The levels of serum Cr and BUN of rats in the cisplatin control group on the 3rd, 5th, and 6th days after cisplatin administration, as well as the score of renal tubular injury degree on the 7th day, were higher than those in the negative control group and the model control group (all P<0.05). The serum Cr levels of rates on the 3rd and 5th days after cisplatin administration, the serum BUN levels on the 5th day in the medium- and high-dose GMDTC groups, the score of renal tubular injury degree, and renal platinum level on the 7th day decreased compared with the cisplatin control group (all P<0.05), while the serum Cr and BUN levels on the 6th day and the whole-blood platinum levels in the high-dose GMDTC group decreased (all P<0.05). The urinary platinum levels of rats in the three GMDTC dose groups increased on the 1st day after GMDTC administration (all P<0.05), but decreased on the 3rd day compared with the cisplatin control group (all P<0.05). The counts of white blood cells, neutrophils, lymphocytes and platelets of rats in the cisplatin control group were lower than those in the model control group (all P<0.05). There was no significant difference in the above indexes of rats between the three GMDTC dose groups and the cisplatin control group (all P>0.05). Conclusion Intravenous administration of GMDTC at doses of 54 or 108 mg/kg body mass effectively reduce the nephrotoxicity of cisplatin-treated rats with LLC-WRC-256 tumors without affecting the antitumor effect of cisplatin.
2.Initial dose and safety of cadmium-antidote GMDTC for intravenous infusion
Qile ZHAO ; Yuting GAO ; Wei HU ; Zhiyong ZHONG ; Xuefeng REN ; Xiaojiang TANG
China Occupational Medicine 2024;51(3):257-264
Objective To investigate the initial dose and safety of intravenous infusion of sodium (s)-2-(dithiocarboxylato((2R,3R,4R,5R,6R)-2,3,4,5,6-pentahydroxyhexyl) amino)-4-(methylthio) butanoate (GMDTC) for the displacement of cadmium. Methodsi) Efficacy test. The New Zealand male rabbits were randomly divided into model group, calcium disodium edetate (EDTA) group and GMDTC low-, medium- and high-dose groups after cadmium poisoning using 2.5 cadmium chloride dihydrate. Rabbits in EDTA group were intravenously injected with EDTA dipotassium at a dose of 93.5 mg/kg body weight, rabbits in the three doses groups were intravenously injected of GMDTC at doses of 12.0, 36.0, and 108.0 mg/kg body weight, respectively. The rabbits in the control group (separate set) and model group were intravenously injected with equal volumes of 0.9% sodium chloride solution, administered for five consecutive days per week for 1, 2, and 4 weeks. ii) Toxicity test. Specific pathogen free SD rats were randomly divided into solvent control group and low-, medium- and high-dose groups. In the acute toxicity test, the rats in the three-dose groups were intravenously injected of GMDTC at doses of 200.0, 800.0 and 3 000.0 mg/kg body weight, respectively. In the long-term toxicity test, the rats in the three-dose groups were intravenously injected GMDTC at doses of 100.0, 500.0 and 2 000.0 mg/kg body weight, respectively, once a day for four consecutive weeks, with a recovery period of four weeks. The rats in the solvent control group were given an equal volume 0.9% sodium chloride solution intravenously at the same time. The maximum tolerated dose (MTD) and no observable adverse effect level (NOAEL) were detected. Resultsi) In the one week treatment experiment, the 24 hours urinary cadmium levels of rabbits in the three doses groups were higher than those in the model group at the same time point (all P<0.05). In the two weeks treatment experiment, the 24 hours urinary cadmium levels of rabbits in medium-dose and high-dose groups at the three time points were higher than those in the model group at the same time point (all P<0.05). In the four weeks treatment experiment, the 24 hours urinary cadmium level on the 19th day of rabbits in the low-dose group was higher than that in the model group at the same time point (P<0.05), and the 24 hours urinary cadmium levels of rabbits in medium- and high-dose groups at the five time points were higher than those in the model group at the same time point (all P<0.05), except for the rabbits of fifth day of the medium-dose group. The kidney cadmium levels of rabbits in the low-dose group after four week of treatment and in the medium- and high-dose groups after one, two, and four weeks of treatment decreased compared with the model group (all P<0.05). No obvious adverse effects were observed during the treatment. ii) The MTD of GMDTC in rats administered intravenously in a single dose was 3 000.0 mg/kg body weight. During the period of intravenous infuseion with GMDTC for four consecutive weeks, the blood drug level reached the peak at the end of the first and last administrations (eight min), and no clinical adverse reactions were observed during this period of time, nor was there any apparent accumulation. The NOAEL for intravenous infusion of GMDTC for four consecutive weeks in rats was 500.0 mg/kg body weight. Conclusion The initial dose of the GMDTC injection in the cadmium poisoning rabbit was 36.0 mg/kg body weight, and the recommended initial dose for human is 480.0 mg/person. Intravenous infusion of GMDTC is characterized by rapid absorption, rapid elimination, and no accumulation.
3.The role of GMDTC in alleviating cisplatin-induced acute kidney injury in rats
Yiran KANG ; Wei HU ; Zhiyong ZHONG ; Xiaojiang TANG
China Occupational Medicine 2024;51(1):31-36
ObjectiveTo investigate the protective effect of N-(2R,3R,4R,5R,6R-pentahydroxyhexyl)-(N-disubstituted sodium formate)-L-methylthio-glutamate sodium (GMDTC) against cisplatin-induced acute kidney injury (AKI) in rats. Methods Specific pathogen free male adult SD rats were randomly divided into the control group, model group, low-dose group and high-dose group, with eight rats in each group. The rats in the latter three groups were injected with cisplatin at a dose of 4 mg/kg body mass through the tail vein to establish an AKI model, while the control group was not treated. Rats in the low-dose and high-dose groups were injected with injectable GMDTC at doses of 108 and 433 mg/kg body mass through the tail vein, respectively, in two hours after intoxication, while the rats in the model group were injected with an equal volume of 0.9% sodium chloride solution, once per day for five consecutive days. The 24-hours urine platinum level at day 1, 3, 5 and the level of whole blood platinum, serum platinum, urinary platinum and renal platinum at day 6 were determined using the inductively coupled plasma-mass spectrometry after GMDTC administration. Serum renal functional indicators and electrolyte level were detected, and renal histopathology was observed at day 6 after GMDTC administration. Results The levels of serum urea, serum creatinine, serum calcium ion, whole blood platinum, serum platinum and renal platinum, and the score of renal tubular injury in the model group were higher than those in the control group (all P<0.05). The 24-hours urinary platinum level at day 1, 3 and 5 after GMDTC administration in the model group was also higher than those in the control group (all P<0.05), and AKI changes were observed in histopathology. The levels of serum urea, serum creatinine, serum calcium ion, whole blood platinum, serum platinum, renal platinum, and renal tubular injury scores of rats in the low- and high-dose groups decreased compared with that in the model group (all P<0.05). The 24-hour urinary platinum levels on the first day after GMDTC administration of rats in the low- and high-dose groups increased compared with that in the model group (all P<0.05), as well as the renal histopathological changes of AKI were improved. However, there was no significant difference in the above-mentioned indicators between the low- and high-dose groups (all P>0.05). Conclusion GMDTC can promote the elimination of platinum in urine, effectively reduce the platinum level in blood and renal tissues, alleviate the pathological damage of renal tubules in rats, and improve the cisplatin-induced AKI.
4.Comparison of short-term curative effects between three fixations of the tibial end in reconstruction of the anterior cruciate ligament
Zhao TANG ; Hui JIANG ; Jia MENG ; Xiaojiang YANG ; Tao YUAN ; Yan LI ; Nirong BAO
Chinese Journal of Orthopaedic Trauma 2023;25(10):897-901
Objective:To compare the short-term curative effects between 3 fixations of the tibial end with an interface screw, an interface screw + a portal nail and an interface screw + a knotless rivet in reconstruction of the anterior cruciate ligament (ACL).Methods:A retrospective study was conducted to analyze the data of 150 patients who had undergone reconstruction surgery for ACL injury at Department of Orthopaedics, Jinling Clinical Medical College, Nanjing Medical University from January 2019 to December 2021. The patients were divided into 3 groups according to their different fixations of the tibial end. In group A of 51 cases subjected to fixation of the tibial end with an interface screw, there were 40 males and 11 females with a mean age of (29.8±10.6) years. In group B of 55 cases whose tibial end was fixated with an interface screw + a portal nail, there were 47 males and 8 females with a mean age of (28.6±6.9) years. In group C of 44 cases whose tibial end was fixated with an interface screw + a knotless rivet, there were 39 males and 5 females with a mean age of (28.6±8.1) years. The 3 groups were compared in terms of International Knee Documentation Committee (IKDC) scoring and Lysholm knee function scoring at 12 and 48 weeks after operation, incidence of local pain at 4 weeks after operation, and stability of the knee at 48 weeks after operation.Results:There was no significant difference in the preoperative general data or follow-up time between the 3 groups, indicating comparability ( P>0.05). At 12 weeks after surgery, in Group B and Group C, the IKDC scores [(74.27±3.32) and (76.48±3.83) points] and Lysholm knee joint scores [(77.65±3.14) and (79.75±5.39) points] were significantly better than those in Group A [(69.73±6.04) and (71.63±3.36) points] ( P<0.05). However, there was no statistically significant difference in the above scores among the 3 groups at 48 weeks after surgery ( P>0.05). The incidence of local pain at the tibial end in group B (9.1%, 5/55) was significantly higher than that in group A (0, 0/51) and group C (2.3%, 1/44) at 4 weeks after surgery, and the results of the anterior drawer test in group A (36 negative cases, 14 cases of grade Ⅰ, and 1 case of grade Ⅱ) were significantly worse than those in group B (50 negative cases, and 5 cases of grade Ⅰ) and group C (40 negative cases, and 4 cases of grade Ⅰ) at 48 weeks after surgery ( P<0.05). Conclusions:In ACL reconstruction, all the 3 fixations of the tibial end can achieve fine short-term curative effects. Fixation with an interface screw + a knotless rivet may lead to a lower rate of ligament relaxation and a higher score of early knee function than fixation with an interface screw, and a lower incidence of local pain at the tibial end than fixation with an interface screw + a portal nail.
5.Primary retroperitoneal soft tissue sarcoma resection combined with nephrectomy: a report 27 cases
Jiaxin LIN ; Dechang DIAO ; Weilin LIAO ; Jiahao WANG ; Xin TANG ; Wenjuan LI ; Hongming LI ; Xiaojiang YI ; Xinquan LU ; Xiaochuang FENG ; Zhaoyu CHEN
Chinese Journal of General Surgery 2023;38(12):905-908
Objective:To investigate the efficacy and safety of retroperitoneal soft tissue sarcoma resection combined with nephrectomy.Methods:The clinical data of 27 cases undergoing retroperitoneal soft tissue sarcoma resection combined with nephrectomy at the Gastrointestinal Tumor Center , Guangdong Provincial Hospital , Traditional Chinese Medicine from Jun 2017 to Aug 2022 were retrospectively analyzed for the indication of nephrectomy, postoperative progression of renal insufficiency and survival rate.Results:Twenty-six cases (96%) achieved R 0/R 1 resection and 1 case nderwent R 2 resection. Six cases underwent combined unilateral nephrectomy and 21 patients underwent combined multi-organ resection with a median number of resections of 4 (2,5). Postoperative pathology suggested that the combined resected kidney was positive for tumor infiltration in 17 cases. Five cases had Clavien-Dindo grade 3 or higher complications and no deaths occurred within 30 days after surgery. At the 90th day after surgery, 19 cases (70%) had decreased renal function ( Z=2.88, P=0.04), with a median decrease of -3.96 (-30.36, 0.31)ml·(min·1.73 m 2) -1, including 8 cases of preoperative Chronic Kidney Disease(CKD)1 stage progression (6 cases of CKD 2 stage, 2 cases of CKD 3 stage); 2 cases of CKD 2 stage progressed to CKD 3 stage; 1 case of preoperative CKD 3 stage progressed to CKD 4 stage. During the follow-up period of 3-38 months, no patient progressed to CKD 5 stage and no patient required dialysis treatment. Conclusion:Retroperitoneal soft tissue sarcoma resection combined with nephrectomy is safe and feasible while improving tumor radicality.
6.Feasibility of a three-sided encapsulation procedure based on fascia anatomy in laparoscopic lateral lymph node dissection for middle and low rectal cancer
Wenjuan LI ; Dechang DIAO ; Jiaxin LIN ; Jiahao WANG ; Weilin LIAO ; Xin TANG ; Jiaxin XIE ; Lin AO ; Xueyang ZHANG ; Xiaojiang YI ; Xiaochuang FENG ; Hongming LI ; Xinquan LU
Chinese Journal of Gastrointestinal Surgery 2023;26(10):968-976
Objective:To explore the feasibility and value of performing a three-sided encapsulation procedure based on fascia anatomy in laparoscopic lateral lymph node dissection (LLND) for middle and low rectal cancer.Methods:This was a retrospective review. The study cohort comprised patients who met the diagnostic criteria for rectal cancer according to the Chinese Guidelines for the Diagnosis and Treatment of Colorectal Cancer, had a short lymph node diameter of >5 mm on the lateral side within the 15 days before surgery, were evaluated as feasible candidates for laparoscopic total mesorectal excision+LLND surgery, had been diagnosed with low or intermediate level rectal cancer, and whose tumor was less than 8 cm away from the anal verge according to pathological examination of the operative specimen. Patients with a history of other malignant tumors of the abdomen or with incomplete follow-up data were excluded. Forty-two patients with middle and low rectal cancer who had undergone lateral lymph node dissection in diagnosis and treatment center of Gastrointestinal Cancer of Guangdong Hospital of Chinese Medicine from Jan.2018 to Dec.2022 were enrolled. There were 24 men (57.1%) and 18 women (42.9%) aged 58.4±11.8 years and the median BMI was 22.5 (19.3–24.1) kg/m 2. The main point of the three-sided encapsulation procedure is to expand the external side medial to the external iliac artery and vein, narrowing the range of exterior side dissection. The anterior-medial side is designed to expand the vesical fascia to define the range of anterior-medial side extension. The internal side is fully extended to the ureterohypogastric nerve fascia; the distal point of the caudal extension reaches the level of the Alcock canal and the bottom reaches the piriformis, enabling dissection of the obturator nerve and No.283 lymph nodes. No.263D lymph nodes are dissected by exposing the internal iliac artery and its branches, dissecting the group No.263P lymph nodes, and severing the inferior vesical artery. Finally, the lateral lymphatic tissue is completely resected. Relevant variables were recorded, including the number of lateral lymph nodes detected, the rate of lymph node metastasis, operation duration, intraoperative blood loss, postoperative complications, postoperative hospital stay, and 3-year overall survival rate. Results:Laparoscopic surgery was successfully completed in all patients with no conversions to open surgery and no intraoperative complications. Twenty-seven (64.3%) of the study patients underwent left-sided LLND, 10 (23.8%) right-sided LLND, and five (11.9%) bilateral LLND, with lymph nodes cleared on both sides. All patients' lymph nodes were examined pathologically. A median of 17.0 (11.7, 26.0) lymph nodes was detected, the median of lateral lymph nodes being 5.0 (2.0, 10.2). The median operation time was 254.5 (199.0, 325.2) minutes. The median intra-operative blood loss was 50.0 (30.0, 100.0) mL. All patients were diagnosed with adenocarcinoma by pathological examination of the operative specimen. Two patients developed postoperative intestinal obstruction, one lymphatic leakage, and one a perineal incision infection. There were no cases of anastomotic leakage. The median postoperative hospital stay was 6.0 (5.0, 7.0) days and the median follow-up time 23.5 (9.0, 36.7) months. During follow-up, three patients (7.1%) died of tumor recurrence and metastasis. Two (4.8%) experienced mild urinary dysfunction, and one (2.4%) had moderate postoperative erectile dysfunction. One patient (2.4%) was found to have prostate and lung metastases 3 month after surgery. The 3-year overall survival rate was 74.4%.Conclusions:Three sided encapsulation is a safe and feasible procedure for LLND, achieving accurate and complete clearance of lateral lymphatic tissue.
7.Feasibility of a three-sided encapsulation procedure based on fascia anatomy in laparoscopic lateral lymph node dissection for middle and low rectal cancer
Wenjuan LI ; Dechang DIAO ; Jiaxin LIN ; Jiahao WANG ; Weilin LIAO ; Xin TANG ; Jiaxin XIE ; Lin AO ; Xueyang ZHANG ; Xiaojiang YI ; Xiaochuang FENG ; Hongming LI ; Xinquan LU
Chinese Journal of Gastrointestinal Surgery 2023;26(10):968-976
Objective:To explore the feasibility and value of performing a three-sided encapsulation procedure based on fascia anatomy in laparoscopic lateral lymph node dissection (LLND) for middle and low rectal cancer.Methods:This was a retrospective review. The study cohort comprised patients who met the diagnostic criteria for rectal cancer according to the Chinese Guidelines for the Diagnosis and Treatment of Colorectal Cancer, had a short lymph node diameter of >5 mm on the lateral side within the 15 days before surgery, were evaluated as feasible candidates for laparoscopic total mesorectal excision+LLND surgery, had been diagnosed with low or intermediate level rectal cancer, and whose tumor was less than 8 cm away from the anal verge according to pathological examination of the operative specimen. Patients with a history of other malignant tumors of the abdomen or with incomplete follow-up data were excluded. Forty-two patients with middle and low rectal cancer who had undergone lateral lymph node dissection in diagnosis and treatment center of Gastrointestinal Cancer of Guangdong Hospital of Chinese Medicine from Jan.2018 to Dec.2022 were enrolled. There were 24 men (57.1%) and 18 women (42.9%) aged 58.4±11.8 years and the median BMI was 22.5 (19.3–24.1) kg/m 2. The main point of the three-sided encapsulation procedure is to expand the external side medial to the external iliac artery and vein, narrowing the range of exterior side dissection. The anterior-medial side is designed to expand the vesical fascia to define the range of anterior-medial side extension. The internal side is fully extended to the ureterohypogastric nerve fascia; the distal point of the caudal extension reaches the level of the Alcock canal and the bottom reaches the piriformis, enabling dissection of the obturator nerve and No.283 lymph nodes. No.263D lymph nodes are dissected by exposing the internal iliac artery and its branches, dissecting the group No.263P lymph nodes, and severing the inferior vesical artery. Finally, the lateral lymphatic tissue is completely resected. Relevant variables were recorded, including the number of lateral lymph nodes detected, the rate of lymph node metastasis, operation duration, intraoperative blood loss, postoperative complications, postoperative hospital stay, and 3-year overall survival rate. Results:Laparoscopic surgery was successfully completed in all patients with no conversions to open surgery and no intraoperative complications. Twenty-seven (64.3%) of the study patients underwent left-sided LLND, 10 (23.8%) right-sided LLND, and five (11.9%) bilateral LLND, with lymph nodes cleared on both sides. All patients' lymph nodes were examined pathologically. A median of 17.0 (11.7, 26.0) lymph nodes was detected, the median of lateral lymph nodes being 5.0 (2.0, 10.2). The median operation time was 254.5 (199.0, 325.2) minutes. The median intra-operative blood loss was 50.0 (30.0, 100.0) mL. All patients were diagnosed with adenocarcinoma by pathological examination of the operative specimen. Two patients developed postoperative intestinal obstruction, one lymphatic leakage, and one a perineal incision infection. There were no cases of anastomotic leakage. The median postoperative hospital stay was 6.0 (5.0, 7.0) days and the median follow-up time 23.5 (9.0, 36.7) months. During follow-up, three patients (7.1%) died of tumor recurrence and metastasis. Two (4.8%) experienced mild urinary dysfunction, and one (2.4%) had moderate postoperative erectile dysfunction. One patient (2.4%) was found to have prostate and lung metastases 3 month after surgery. The 3-year overall survival rate was 74.4%.Conclusions:Three sided encapsulation is a safe and feasible procedure for LLND, achieving accurate and complete clearance of lateral lymphatic tissue.
8.Advances in machine learning in suicide prediction on online social platforms
Hanxiao WANG ; Aijia KANG ; Yubao ZHAO ; Furong ZHAO ; Xiaojiang JIANG ; Fengyi HAO ; Xiangdong TANG
Sichuan Mental Health 2021;34(6):580-584
This article systematically reviews the research results related to the machine learning based suicide ideation prediction on social networking platforms, so as to provide references for group and individual suicide prediction. This article will address the current states (issues of algorithm accuracy and efficiency, privacy leakage and stigma) and limitations of machine learning based suicide prediction on different platforms (light blogging, acquaintance social platforms, forums, picture and video sharing applications and clinical databases).
9. New Zealand rabbit model of cisplatin-induced acute kidney injury
Wei TANG ; Zhiyong ZHONG ; Ming DONG ; Shenglai LIU ; Manling LUO ; Jide LIU ; Xuefeng REN ; Xiaojiang TANG
China Occupational Medicine 2018;45(06):702-707
OBJECTIVE: To establish a New Zealand rabbit model of acute kidney injury induced by cisplatin. METHODS: A total of 24 male New Zealand rabbits were randomly divided into control group,low-,medium-and high-dose cisplatin group according to the body mass. Rabbits were injected with cisplatin at 0. 0,1. 0,2. 0,4. 0 mg/kg body weight by auricular vein. Rabbits in low-dose group was continuously injected for 5 days,medium-dose group was continuously injected for 3 days,and the high-dose group was injected for once per day. Rabbits in the control group did not receive any treatment. Blood was collected from the middle ear artery and 24 h urine was taken before exposure and on day 1,day 3,day 5 and day 7 of injection. The serum creatinine( Scr) and urea nitrogen( BUN) were detected by colorimetric method,and 24 h urine kidney injury molecule 1( KIM-1) was measured by enzyme-linked immunosorbent assay. Plasma platinum,24 h urinary platinum and renal platinum level were detected by inductively coupled plasma mass spectrometry.At the end of the experiment,rabbits were sacrificed and the left kidney was taken for histopathological examination.RESULTS: The body mass of rabbits of the low-,medium-and high-dose groups on day 7 after cisplatin exposure was lower than that of the control group( P < 0. 05),and lower than that of the same group before exposure( P < 0. 05). After 3 days of exposure,the Scr level in each dose group was higher than that of the control group( P < 0. 05),the Scr level on day 3and day 5 in medium-and high-dose groups were higher than that of the low-dose group( P < 0. 05). The BUN levels on day 3 and day 5 in medium-and high-dose group were higher than that of the control group and low-dose group( P <0. 05),the BUN levels on day 7 in three dose groups were higher than that of the control group( P < 0. 05). The levels of plasma platinum and 24 h urinary platinum in the three doses groups of New Zealand rabbits on day 1,day 3,day 5 and day 7 after exposure were higher than that of the control group( P < 0. 05),and were higher than the pre-treatment levels of the same group( P < 0. 05). The level of 24 h urinary KIM-1 in the meclium-dose group of New Zealand rabbits was higher than that of the control group on day 3 of exposure( P < 0. 05). The level of 24 h urinary KIM-1 in the mediumdose group of New Zealand rabbits on the 5th day after exposure was higher than that of the control group( P < 0. 05). The renal platinum levels in the three groups of New Zealand rabbits were higher than that in the control group( P < 0. 05).The pathological changes of rabbit kidney caused by cisplatin are mainly tubular dilatation,protein cast,alkalophilic and interstitial nephritis. CONCLUSION: Cisplatin can induce acute kidney injury in rabbits,and the degree of injury is dosedependent. The dose of 1. 0 mg/kg body weight continuous injection for 5 days is closely related to clinical use of cisplatin,which is recommended for model establishment.
10. Study on the Specific Complexation of GMDTC and Metal Ion
Zhiyong ZHONG ; Wei TANG ; Guoding LI ; Xiaolin RUAN ; Chenzi ZHANG ; Guangxian LI ; Fan FEI ; Xiaojiang TANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2018;36(6):408-412
Objective:
Study the response of GMDTC to cadmium ions and metal ions in vivo to determine whether GMDTC are specifically complexed with cadmium ions to provide a reference for the safety and dfficacy of GMDTC.
Methods:
Complexometric titration, HPLC and HPLC-MS were applied to research the complexation reaction of GMDTC and various metal ions. The molecular ion peak of GMDTC, GMDTC-Cd complex and GMDTC-Pb complex also detected by LC-MS. Additionally, the initial structure was determined by DFT simulation method.
Results:
Results of complexometric titration and HPLC detection showed that GMDTC characteristic absorption peak area was proportional to the concentration of itself and there was no color change and peak time change when the GMDTC mixed with Ca2+, Fe2+, Mg2+, Zn2+. However, the color changed to black transition when the GMDTC mixed with Cu2+ and the color changed from yellow precipitate to light yellow transparent transition when GMDTC mix with Hg2+. Moreover, the peak area as well as the retention time has changed a lot which indicated that a chemical reaction has already happened. When the GMDTC mixed with Cd2+ and Pb2+, the color has changed from pale yellow to colorless transparent and the peak area of GMDTC has increased a lot. Finally, the GMDTC-Cd complex ratio both of which are 2:1 were calculated based on the results of LC-MS instrument and atomic calculations.
Conclusion
The specific cadmium chelating agent GMDTC can not react with the Ca2+, Fe2+, Mg2+, Zn2+, but it can react chemically with Cu2+ and Hg2+, even specific complex with Pb2+ and Cd2+.

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