Narrow Results

It is well-known that the mineralocorticoid action of glycyrrhizin, which is the major component of Glycyrrhiza uralensis, is caused by a defect in the conversion of cortisol to cortisone by the inhibition of 11-β-hydroxysteroid dehydrogenase enzyme activity. In the present study, we investigated the mechanisms of salt and water retention in the kidney of rats administered excess amounts of glycyrrhizin (200 mg/kg/day, p.o.). Up-regulation of aquaporin (AQP) 2 and 3 water channels was detected in the renal inner and outer medulla by Western blot analysis in rats treated with glycyrrhizin for 0.5, 1 and 2 consecutive weeks. Our results show that urine flow rates and sodium excretion rates in glycyrrhizin-treated rats were decreased significantly, but creatinine clearance (Ccr) was not altered. The decreases of urine volume and urinary sodium excretion in glycyrrhizin-treated rats were reversed by a 2-week injection of spironolactone, which is a well-known mineralocorticoid receptor (MR) blocker. These results suggest that the retention of water and salt in glycyrrhizin-treated rats is, at least in part, accounted for by the increased expression of AQP 2 and 3 in the kidney, which may be causally related to the MR.

The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na⁺, K⁺, Cl^-, creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

The aim of the present study was to identify the selective therapeutic effects of Corni Fructus (Cornus officinalis Sieb. et Zucc.) on different organs in streptozotocin (STZ)-induced diabetic rats. Diabetes in rats was induced by intraperitonal injection with STZ at a dose of 30 mg/kg body weight (bw) for 3 days (once per a day). STZ-induced diabetic rats were orally administrated Corni Fructus (CF) extract at 300 mg/kg or metformin at 250 mg/kg daily for 4 weeks. Blood glucose and triglyceride (TG) in sera and urine total volume were measured. Histopathological changes of different organs, pancreas, liver, kidney, and lung tissues were observed by H&E staining. The expression of insulin and α-smooth muscle actin (α-SMA) was investigated in pancreas, and kidney by immunohistochemistry, respectively. The results revealed that CF extract significantly decreased the serum levels of blood glucose, and TG, and also urine total volume in STZ-induced diabetic rats. The histological examinations revealed amelioration of diabetes-induced pancreas injury including pathological changes of the Langerhans's islet and glomerular with their loss after the administration of CF extraction. Moreover, the administration of CF extract increased the numbers of insulin releasing beta cells in pancreas and also inhibited the expression of α-SMA in kidney of STZ-induced diabetic rats. On the other hand, CF extract showed no effect on the pathological damages of liver and lung in STZ-induced diabetic rats. These results demonstrated that CF extract may have a selective therapeutic potential through the control of hyperglycemia, and the protection of pancreas and kidney against diabetic damage.

Acute kidney injury (AKI) is a major public health problem worldwide that still lacks effective treatments. Recent studies have suggested that ferroptosis is a key mediator of AKI due to its activation of lipid peroxidation. Therefore, we hypothesized that antiferroptosis agents might be a novel potential therapeutic strategy for AKI. Herein, we demonstrated that liquiritigenin (LG), an active ingredient of liquorice, improves renal function by inhibiting vitamin K epoxide reductase complex subunit 1 (VKORC1)-mediated ferroptosis, both in vivo and in vitro. In a folic acid-induced murine AKI model, after a single pre-treatment intravenous injection, LG markedly alleviated the loss of renal function through suppressing ferroptosis induced by iron accumulation. LG prevented mitochondrial morphological changes and upregulated glutathione and glutathione peroxidase 4 levels, while downregulating malonaldehyde and divalent iron levels. An in vitro RNA-sequence analysis suggested that the protective role of LG may involve upregulation of VKORC1. Moreover, knockdown of VKORC1 diminished the renal protective and antiferroptosis roles of LG. Collectively, our findings demonstrated that LG protected against AKI by inhibiting VKORC1-mediated ferroptosis. This suggests that inhibiting ferroptosis might be a novel therapeutic approach in the future.

This study investigates the long-term effects of PEG-PLA nano-artificial cells containing hemoglobin (nanoRBCs) on renal function and renal histology after a one-third blood volume toploading in rats. The experimental rats received one of the following infusions: NanoRBCs in Ringer’s lactate solution, stroma-free hemoglobin (SFHb), polyhemoglobin (polyHb) or autologous rat whole blood (rat RBCs). Blood samples were taken before infusions and on Days 1, 7 and 21 after infusions for biochemistry analysis. Rats were sacrificed on Day 21 after the infusions and their kidneys were excised for histology examination. Infusion of SFHb induced significant decrease in renal function damage as evidenced by elevated serum urea, creatinine and uric acid throughout the 21 days. Kidney histology in the SFHb infusion group revealed focal tubular necrosis and intraluminal cellular debris in the proximal tubules, whereas the glomeruli were not observed to be damaged. There was no abnormalities in renal biochemistry or histology in all the other groups (nanoRBCs, polyHb, Ringer’s lactate solution and rat RBCs). In conclusion, the injections of nanoRBCs did not have adverse effects on renal function or remal histology.