Exposure to cadmium (Cd) has harmful effects on the liver and kidney. Resveratrol (RES) is an herbal substance that functions as a protective mediator. This study aimed to investigate the effects of RES on the histology of liver and kidney in Cd-exposed mice. Male mice were divided into 4 groups daily receiving normal saline (1 mL normal saline/d), Cd (1 mg/kg/d), RES (20 mg/kg/d), and Cd plus RES, respectively. After 4 weeks, the liver and kidney components were evaluated using stereological methods. The total volume and number of hepatocytes, and volume of fibrous tissue were respectively increased by 34%, 58%, and a 3-fold in the Cd-exposed mice in comparison to the control animals (P<0.03). On the other hand, the volume of the main vasculature (sinusoids and central veins) was decreased by 36% in the Cd group compared to the control mice (P<0.03). Considering the kidney, the results showed a 3-fold increase in the total glomeruli volume and a 7-fold increase in fibrous tissue in the Cd-treated group compared to the control mice (P<0.03). After Cd treatment, a 32% reduction was observed in the volume and length of the proximal and distal convoluted tubules. RES-treatment alone did not induce any structural changes. In comparison to the Cd group, an increase in the normal components of the liver and kidney and a decrease in the formation of the fibrous and degenerated tissues were observed in the Cd+RES-treated mice (P<0.03).
Objective: Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in adults. However, there is not a satisfactory treatment for MN. This study aimed to evaluate the effect of Houttuyniae Herba Extract (HHE) on MN induced by cationic bovine serum albumin (cBSA). Methods: Mice were divided into 4 groups. The first group, Normal, was injected with saline. The second group, Control, was treated with cBSA (10mg/kg i.p) only. The third group, HHE-250, was treated with cBSA (10mg/kg i.p) and HHE (250mg/kg, p.o). The fourth group, HHE-500, was treated with cBSA (10mg/kg i.p) and HHE (500mg/kg, p.o). After treatment for 4 weeks, we measured change of body weight, 24 hrs proteinuria, serum albumin, total cholesterol, triglyceride, BUN, creatinine, IgA, IgM, IgG, TNF-${\alpha}$, IL-1${\beta}$ levels and the mRNA expression of IFN-${\gamma}$, IL-6, and IL-10. The morphologic changes of renal glomeruli were also observed with a light microscope and an electron microscope. Results: The levels of 24 hrs proteinuria and serum triglyceride, BUN, IgG, TNF-${\alpha}$, IL-1${\beta}$ significantly decreased in both HHE groups, while the level of serum albumin significantly increased in both HHE groups. The mRNA expression of IFN-${\gamma}$ and IL-6 in splenocytes considerably increased in both HHE groups. The mRNA expression of IL-10 in splenocytes considerably decreased in both HHE groups. In histological findings of kidney tissue, thickening of GBM decreased in both HHE groups. Conclusions: This study shows that HHE might be effective for treatment of acute stage MN. More clinical data and studies are to be done for efficient application.
This experiment was carried out to study the toxic effect of solublized methylcellulose (MC). Sprague-Dawley rats were dosed with 1%(w/v) MC in 0.9% saline by gavage at a dose of 10ml/kg b.w/day or by intravenous injection at a dose of 5ml/kg b.w/day for 28 days. Clinical signs were observed once a day. Body weights, water and food consumptions were measured and urinalysis was performed several times during the experiment. Rats were sacrificed on days 3, 7, 15 and 28 for hematology, blood chemistry, organ weights and histopathology. The relative weight of the spleen and foamy cells of the spleen were increased in the gavage group. Body weight gain, food consumptions, the values of RBC, Hb, MCH, Hct, serum proteins, glucose, bilirubin, AST, and ALP were decreased in I.V. treatment group. On the other hand, water consumptions, the values of serum cholesterol, creatinine, and BUN were increased. Microscopic findings were granulomas, distended sinusoids, and hypertrophy of Kupffer cells with vacuoles in the liver. Spleen exhibited granuloma, increased extramedullary hematopoiesis, and congestion. Kidney exhibited foamy cells in the glomeruli, distension of the tubules. The findings appeared more severe when the treatment was extended. In conclusion, MC solution is not a safe vehicle for intravenous administration because of the toxic effects on the liver, kidney and spleen. In addition, a long-term and large dosage of oral administration of MC appears to be unsafe also and needs to be investigated further.
Experimental radiation nephritis was produced in 15 rabbits by X-irradiation. About $2,000{\gamma}$ (tissue doses) were given to both kidneys of a rabbit in 5 days. Other tissues and organs except both kidneys were protected with 2mm thickened lead plates. 5 weeks after the last irradiation, blood pictures, blood pressures, B.U.N., serum creatinine, Ca, Mg, Fe levels and serum erythropoietin activity of the irradiated rabbits were studied. After finishing above studies, rabbits were sacrificed and both kidneys were removed and examined histopathologically. Same laboratory and pathological studies were performed in 6 control rabbits. In this study, the author obtained following results. 1) Both kidneys of rabbitis with experimental raditation nephritis showed marked histopathological changes, i.e.: renal tubules showed diffuse cloudy swelling, impacted intraluminal hyaline casts and focal precipitations of lime salts on the tubular epithelium. Diffuse interstitial fatty necrosis and various degrees of fibrotic infiltrations on the interstitium were also seen in association with focal lymphocytic infiltrations. Hyaline degenerations were observed on the glomeruli and small vessels. 2) Experimental radiation nephritis rabbits showed marked lowering in R.B.C. counts, decreased hemoglobin levels, low hematocrit values and leucopenia in comparison with those of control rabbits. (P<0.01). (Table 1 & 2). 3) Mild proteinuria were observed in experimental radiation nephritis in rabbits. 4) The levels of B.U.N. and serum creatinine increased in experimental radiation nephritis. (P<0.01). (Table 1,3 & 4) 5) The levels of serum Ca and Mg Showed no statistical difference in comparison with those of control rabbits. (P>0.05) (Table 3 & 4). 6) No statistical correlations were observable between the levels of B.U.N. and Hb. values. (${\gamma}=-0.223$) No close correlations (${\gamma}=-0.328$) were noticed between the levels of B.U.N. and serum iron levels. 7) Erythropoietin activity (R.B.C. $^{59}Fe$ Incorporation) was measured by the modified Fried method. No change in its activity was noticed in radiation nephritis group comparing with that of the control group. (P>0.05). (Table 1,3 & 5). 8) Carotid artery blood pressures showed also no difference. (P>0.05). (Table 1 & 2).
Objective : Membranous nephropathy(MN) is one of the most common causes of nephrotic syndrome in adults. MN has been defined as granular subepithelial deposition of IgG immune complexes along the glomerular basement membrane(GBM). However, there is not a satisfactory treatment for MN. We aimed to identify the effect of Impatiens balsamina Linne(IBL) treatment on cationic bovine serum albumin(cBSA)-induced MN in a mouse model. Methods : Mice were divided into 4 groups. The normal group was injected with saline. The Control group was treated with cBSA(50 mg/kg i.p) only. The third group IBL-100, was treated with cBSA(50 mg/kg, i.p) and IBL(100 mg/kg, p.o). The fourth group IBL-400, was treated with cBSA(50 mg/kg, i.p) and IBL (400 mg/kg, p.o). After cBSA and IBL treatment for 6 weeks, we measured change of body weight, proteinuria, serum albumin, total cholesterol, triglyceride, BUN, creatinine, IgA, IgM, IgG, TNF-${\alpha}$, IL-6 and IL-$1{\beta}$ levels. The morphologic changes of renal glomeruli were also observed with a light microscope. Results : The level of proteinuria significantly decreased and serum albumin increased in groups treated with cBSA and IBL extract compared with the control. The levels of serum triglyceride, BUN, IgG, TNF-${\alpha}$, IL-$1{\beta}$ significantly decreased in both IBL groups. In histological findings of kidney tissue, thickening of GBM decreased in both IBL groups. Conclusions : This study shows that IBL might be effective for treatment of acute stage MN. More clinical data and studies are to be done for efficient application.
Renal failure is one of the main causes of economic impacts in the poultry industry and complex syndrome with different severity of clinical signs caused by multiple nephropathogenic factors such as infectious bronchitis viral infection and excess salt and calcium in diet. To evaluate the correlation between severity of renal failure and the causative nephropathogenic factors, one-day-old specific pathogen free chicks were treated with either single causative factor or multiple causative factors described as above. Each group was designed as control for non-treated control, IB for infectious bronchitis virus (IB virus) infection, IBHNa for IB virus infection with high diet salt, IBHCa for IB virus infection with high diet calcium, IBHNC for IB virus infection with high diet salt and calcium, HNa for high diet salt, HCa for high diet calcium and HNC for high diet salt and calcium. Chickens were inoculated with IB virus at 1-day-old and remained on their respective diets until 21 day of age. The high dietary salt feeding groups such as IBHNa, IBHNC, HNa, HNC increased water intake, watery diarrhea, general subcutaneous edema and the high dietary calcium feeding groups such as IBHCa and IBHNC showed severe visceral gout. Two more than treated groups caused high mortality in comparison with the single treated groups. IB virus exposure significantly increased urate deposition and lymphocytic interstitial nephritis. Especially urate deposition dramatically increased when excess diet calcium was combined together. In excess diet salt treated groups enlarged edematous kidneys were observed and hypertrophy of glomeruli were showed. These results suggest that IB virus enhanced the incidence and severity on chicken renal failure clearly related to the quantity of salt and calcium.
This study was carried out to investigate the effect of selenium on the adriamycininduced renal lesions in male Sprague Dawley rats. A total of 60 Sprague-Dawley male rats were divided into 2 control groups(C1: saline, C2: selenium) and 2 treatment groups(T1: adriamycin, T2: adriamycin+selenium). The rats of the C1 and T1 groups were given normal saline(0.15ml/rat), the rats of the C2 and T2 groups were given sodium selenite(0.5mg/kg) intraperitoneally three days a week for 4 weeks. The treatment groups were dosed intraperitoneally with adriamycin(2mg/kg/day) five days at the second week. Animals were sacrificed at the 1st week, 2nd week and 3rd week after dosing with adriamycin. The morphologic abnormalities of the glomeruli and tubules in the kidney of male rats were examined histopathologically and electron microscopically.The results obtained were as follows : The mean body weight of adriamycin dosed group was significantly decreased as compared with that of control group at 4th week(p<0.05). In adriamycin and selenium dosed group, the mean body weight was decreased until the end of 2nd week but gradually increased from 3rd to 4th week. The histopathological findings of the renal corpuscle in adriamycin dosed group were parietal epithelial cell proliferation, vacuolization of glomerulus, and thickened basement membrane of the parietal epithelium. Proximal convoluted tubules were significantly dilated and the lumens were filled with renal cast. These lesions were generally not very significant in the rats given adriamycin and selenium. The electron microscopical findings of the renal glomerulus in the adriamycin dosed group were focal loss and fusion of the pedicels of the podocyte, and some vacuoles in the cytoplasm of the podocytes. There were numerous cytoplasmic vacuoles in the proximal and distal convoluted tubular cells. However, these ultrastructural changes were not significantly observed in the renal tubules of the rats of adriamycin and selenium dosed group. These results suggest that selenium may act as an inhibitor of the renal lesions induced by adriamycin in male rats.
Calcineurin (CaN) is activated in diabetes and plays a role in glomerular hypertrophy and extracellular matrix (ECM) accumulation. Here, kidneys from diabetic model mice were investigated for the expression of the regulator of CaN 1 (RCAN1) isoform 4 (RCAN1.4) which had been shown to be transcriptionally upregulated by CaN activation. We found the increased immunoreactivity for RCAN1 in the glomerular cells of db/db mice and streptozotocin-induced diabetic mice. In concordance, the expression of RCAN1 protein and RCAN1.4 mRNA were elevated in the whole kidney sample from db/db mice. Interleukin-$1{\beta}$ (IL-$1{\beta}$), tumor necrosis factor-${\alpha}$, and glycated albumin (AGE-BSA) were identified as inducers of RCAN1.4 in mesangial cells. Pretreatment of cyclosporine A blocked the increases of RCAN1.4 stimulated by IL-$1{\beta}$ or AGE-BSA, suggesting that activation of CaN is required for the RCAN1.4 induction. Stable transfection of RCAN1.4 in Mes-13 mesangial cells upregulated several factors relevant to ECM production and degradation. These results suggested that RCAN1.4 might act as a link between CaN activation and ECM turnover in diabetic nephropathy.
This study was performed to investigate the therapeutic effects of Hovenia dulcis Thunberg (HDT) and HDTmix extracts on the biochemical analysis, histopathology and histomorphometry of liver and kidney in carbon tetrachloride $(CCl_4)$ administrated rats. Extract was prepared by autoclave ($121^{\circ}C$, 15 psi, 3 hours) and filtered with nylon cloth and filter paper then freezing dried. In blood chemistry analysis, HDTmix group, aspartate aminotransferase and alanine aminotransferase were significantly (p<0.01) decreased compared to the $CCl_4$ group, on 3rd day, respectively. In histologic and histomorphometry analysis, the $CCl_4-related$ hepatopathies and nephropathies were dramatically decreased (3rd, 5th day), and well corresponded to the histopathological changes significantly (p<0.01) decreases of degenerative regions, degenerative cells and glomeruli were detected in liver and kidney with significantly decreases of $CCl_4$ group. HDTmix group, quite similar effects on the liver and kidney were observed compared to that of HDT extracts group but more favorable efficacies were detected especially HDTmix also inhibit the hepatopathies (1 day), in which HDT extract does not showed any inhibit effects.
In this study, the effect of verapamil (VER) on cyclosporin A (CsA)-induced nephrotoxicity was investigated in uninephrectomized rats. Male Wistar rats were administered CsA (50 mg/kg/day, p.o.) or VER (0.5 mg/kg/day, i.p.) with CsA (50 mg/kg/day, p.o.) for 20 days. The urinary N-acetyl-$\beta$-D-glucosaminidase (NAG) activity along with BUN, serum creatinine, creatinine clearance (CLcr), body weight, and 24 hr-urine output were measured and histopathologic changes of kidney were evaluated by light and electron microscopy. The results obtained from this study can be summarized as follows: While NAG activity, BUN and serum creatinine was progressively increased and CLcr significantly decreased in CsA group, VER almost signifi-cantly (p<0.05) suppressed and normalized CsA-induced changes in VER+CSA group. While urine output increased until 12th days and thereafter progressively decreased in CsA group, it gradually increased in control and VER+CSA group. While body weight progressively made a gain in control and VER+CSA groups, it significantly (p<0.05) lost in CsA group. On light microscopy, the glomerular hyperemia and proximal convoluted tubular (PCT) dilatation, focal tubular cell vacuolation and necrosis were clearly evident in CsA group, but, were not seen in other groups. Ultrastructural studies revealed thickened glomerular endothelium and basal lamina of capillary, irregular shaped pedicels of podocytes, indistinct slit pores and narrowed bowman's space. The large oval vacuoles with dense debris and phagosome were distributed in apical zone and deformed microvilli and mitochondria were seen in the PCT cell of CsA group. But, glomeruli and PCT cell were relatively preserved in normal apperance in other groups. In conclusion, it is suggested that verapamil has a protective effect on cyclosporine-induced nephrotoxicity in uninephrectomized rats.
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