The role of GMDTC in alleviating cisplatin-induced acute kidney injury in rats
Objective To 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.
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