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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Acute Kidney Injury, Animals, Apoptosis, Cell Adhesion, Cell Adhesion Molecules, Cell Line, Cell Movement, Diterpenes, Glucosamine, Humans, Ischemia, Kidney, Kidney Tubules, Leukocytes, Lipid Peroxidation, Male, Molecular Targeted Therapy, Necrosis, Oxidative Stress, Rats, Sprague-Dawley, Reperfusion Injury.
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Does renal-targeting triptolide-glucosamine conjugate exhibit lower toxicity and superior efficacy in attenuation of ischemia/reperfusion renal injury in rats? Context: We previously reported a novel triptolide (TP)-glucosamine conjugate (TPG) that specifically accumulated in kidneys and protected renal function from acute ischemia/reperfusion (I/R) injury in rats. In this study we further examined the molecular mechanisms underlying the renoprotective action of TPG. The renal-targeting of TPG was investigated in a human proximal renal tubular epithelial cell line (HK-2) by measuring cell uptake of TP or TPG. The effects of TP or TPG on cell cycle distribution and apoptosis rate of HK-2 cells were assessed, and the activities of caspase-3 and caspase-9 were also measured. SD rats were subjected to bilateral renal ischemia by temporarily clamping both renal pedicles. The rats were administered TP (4.17 μmol·kg The uptake of TPG in HK-2 cells was 2-3 times higher than that of TP at the concentrations tested. Furthermore, TPG targeting the proximal tubules was mediated through interactions with megalin receptors. TP (40-160 nmol/L) concentration-dependently increased G
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The renal-targeting TPG is more effective and less toxic than TP, in amelioration of I/R-induced rat renal injury, which may provide a new avenue for the treatment of acute kidney injury. Final Decision: yes