Renal Weight Research Articles

Analysis of the Decrement of Renal Weights in Adult Male Rats after Long Term Lithium Carbonate Ingestion

Analysis of the Decrement of Renal Weights in Adult Male Rats after Long Term Lithium Carbonate Ingestion

Moringa oleifera-based feed supplement protects against renal ischaemia/reperfusion injury via downregulation of Bax/caspase 3 signaling.

Ischaemia/reperfusion (I/R) may lead to acute kidney injury via the induction of oxidative stress. On the other hand, Moringa oleifera has been reported to exert antioxidant activities. This study was designed to assess whether or not Moringa oleifera-based feed supplement could prevent I/R-induced renal injury. Renal I/R was induced by occluding the right renal artery for 30 min followed by a 2-h reperfusion. Renal I/R led to increased absolute renal weight and renal organo-somatic weight index. Renal I/R also caused distortion of renal histoarchitecture and impaired renal function evidenced by elevated serum creatinine and blood urea nitrogen. In addition, renal I/R significantly elevated renal levels of hydrogen peroxide, MDA, and advanced oxidation protein products, but suppressed the levels of reduced glutathione, protein thiol, and non-protein thiol, and the activities of superoxide dismutase and glutathione peroxidase. In addition, renal I/R up-regulated myeloperoxidase activity and the renal levels of NO, TNF-α, and IL-6. Renal I/R also up-regulated Bax and caspase 3 expression in the kidney. Furthermore, I/R-driven structural and biochemical alterations were markedly inhibited by Moringa oleifera-based feed supplement. These results suggest that Moringa oleifera-based feed supplement may preserve the gross and histoarchitectural integrity of the kidney as well as renal function via downregulation of Bax/caspase 3 signaling by targeting oxidative stress, inflammation and apoptosis in the kidney of I/R rat.

Development rat models of nephrotoxic: A pre-clinical test model to discover nephroprotective agents

Background: The use of drugs, including aminoglycoside drugs and anticancer drugs, is one of the things that can cause toxicity to the kidneys. Therefore, the development of agents that function as nephroprotectors continues to be researched. Objective: This study aims to obtain a nephrotoxic experimental animal model for testing nephroprotective agents. Method: The treatment was normal group, groups given a single dose of Cisplatin 7 mg/kgBW i.p (Cis), Doxorubicin single dose 25 mg/kgBW i.p (Dox-25), Doxorubicin repeated dose 4 mg/kgBW i.p twice/week for two weeks (Dox-4 repeated dose), and Gentamicin single dose 112 mg/kgBW i.p (Gen). The nephrotoxic effect was assessed by the parameters of kidney weight ratio, Ureum, Creatinine and Albumin levels in rat serum. Result: The nephrotoxic effect was indicated by an increase in the renal weight ratio of the Cisplatin; Dox-25, Dox-4 repeated, and Gen groups than normal, respectively. There was an increase in serum BUN levels, an increase in serum creatinine, and a decrease in serum albumin levels compared to the normal group. Conclusion: Cisplatin, Doxorubicin and Gentamicin have nephrotoxic effects. The administration of a single dose of cisplatin at 7 mg/kg BW gave the strongest nephrotoxic effect, making it appropriate as a model of acute nephrotoxicity in rats.

MicroRNA-630 alleviates inflammatory reactions in rats with diabetic kidney disease by targeting toll-like receptor 4.

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus. Renal tubular epithelial cell (TEC) damage, which is strongly associated with the inflammatory response and mesenchymal trans-differentiation, plays a significant role in DKD; However, the precise molecular mechanism is unknown. The recently identified microRNA-630 (miR-630) has been hypothesized to be closely associated with cell migration, apoptosis, and autophagy. However, the association between miR-630 and DKD and the underlying mechanism remain unknown. To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats. Streptozotocin was administered to six-week-old male rats to create a hyperglycemic diabetic model. In the second week of modeling, the rats were divided into control, DKD, negative control of lentivirus, and miR-630 overexpression groups. After 8 wk, urine and blood samples were collected for the kidney injury assays, and renal tissues were removed for further molecular assays. The target gene for miR-630 was predicted using bioinformatics, and the association between miR-630 and toll-like receptor 4 (TLR4) was confirmed using in vitro investigations and double luciferase reporter gene assays. Overexpression of miR-630 in DKD rats led to changes in body weight, renal weight index, basic blood parameters and histopathological changes. The expression level of miR-630 was reduced in the kidney tissue of rats with DKD (P < 0.05). The miR-630 and TLR4 expressions in rat renal TECs (NRK-52E) were measured using quantitative reverse transcription polymerase chain reaction. The mRNA expression level of miR-630 was significantly lower in the high-glucose (HG) and HG + mimic negative control (NC) groups than in the normal glucose (NG) group (P < 0.05). In contrast, the mRNA expression level of TLR4 was significantly higher in these groups (P < 0.05). However, miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG + miR-630 mimic group than in the HG + mimic NC group (P < 0.05). Furthermore, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 were significantly higher in the HG and HG + mimic NC groups than in NG group (P < 0.05). However, the levels of these cytokines were significantly lower in the HG + miR-630 mimic group than in the HG + mimic NC group (P < 0.05). Notably, changes in protein expression were observed. The HG and HG + mimic NC groups showed a significant decrease in E-cadherin protein expression, whereas TLR4, α-smooth muscle actin (SMA), and collagen IV protein expression increased (P < 0.05). Conversely, the HG + miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4, α-SMA, and collagen IV protein expression than in the HG + mimic NC group (P < 0.05). The miR-630 targets TLR4 gene expression. In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC. Additionally, rats treated with miR-630 agomir showed significant reductions in urinary albumin, blood glucose, TLR4, and proinflammatory markers (TNF-α, IL-1β, and IL-6) expression levels (P < 0.05). Moreover, these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells. MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4, and has a protective effect on DKD.

Melatonin alleviates renal injury in diabetic rats by regulating autophagy.

Melatonin (MLT) is a biologically active indoleamine involved in regulating various biological rhythms, which is deficient in individuals with Type 2 diabetes. The present study examined the effects of MLT on diabetic neuropathy (DN). Diabetic rats received MLT treatment for 12weeks, after which changes in kidney histology, oxidative damage, mitochondrial morphology and autophagy were measured. The glucose tolerance‑ and isoflurane tolerance‑area under the curve (AUC) values and the relative renal weight index (RI) in the diabetes mellitus (DM) group of rats were significantly higher compared with those in the control group. A significant increase in malondialdehyde (MDA) content, and decreases in the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH‑Px) and GSH were demonstrated in the kidneys of DM rats compared with those in the control rats. Histological staining of DM rat kidney tissue with hematoxylin and eosin, Masson's trichome and Periodic acid‑Schiff demonstrated glomerular and tubule lesions, and an increase in collagen compared with control rats. Protein expression levels of LC3II, P62, collagen IV (COL‑IV) and α‑SMA were increased in DM rats and HG‑induced NRK‑52E cells compared with those in the control groups. Phosphorylation of AMPK was reduced, whereas phosphorylation of PI3K, Akt and mTOR were increased invivo and invitro. Notably, MLT treatment significantly reduced glucose tolerance‑AUC and RI, decreased MDA content, and increased SOD, CAT, GSH‑Px and GSH activity. Glomerular and tubule lesions improved, collagen was decreased and mitochondrial damage was alleviated by MLT treatment. MLT treatment also decreased the protein expression levels of LC3II, P62 and COL‑IV, whereas the phosphorylation of AMPK was significantly increased, which inhibited the phosphorylation of PI3K, AKT and mTOR invivo and invitro. These results demonstrated that MLT protects against DN and NRK‑52E cell injury through inhibiting oxidative damage and regulating autophagy via the PI3K/AKT/mTOR signaling pathway.

Patchouli alcohol against renal fibrosis of spontaneously hypertensive rats via Ras/Raf-1/ERK1/2 signalling pathway.

The present study was designed to obverse the protection of patchouli alcohol (PA) ameliorates hypertensive nephropathy in spontaneously hypertensive rats (SHR) and reveals potential mechanism. Briefly, the adult spontaneously hypertensive rats (SHR) or Wistar-Kyoto (WKY) rats (half male and half female) were intragastric gavaged or not with PA (80, 40 and 20 mg/kg) for 8 weeks. Body weight, blood pressure (BP), renal weight, renal function and renal morphology were measured. Further, western blotting and immunohistochemical analysis were used to study the underlying mechanism. Compared with the WKY group, plasmatic levels of renin, angiotensin II (Ang-II), transforming growth factor beta 1(TGF-β1), plasminogen activator inhibitor-1(PAI-1), creatinine (Cr), blood urea nitrogen (BUN), renal index, mRNA levels of ERK1/2 and α-SMA were significantly increased in SHR. Histology results showed that renal tubular injury and tubulointerstitial fibrosis occurred in SHR. After administration, SBP of captopril group decreased at each week after administration, especially at 3, 5, 6 7 and 8 weeks (P < 0.05 or P < 0.01). There is no significant effect was assessed in the olive oil group. Decreased plasma Cr, Renin, Ang-II, TGF-β1, PAI-1, SCFAs and Renin, TGF-β1, PAI-1 in renal tissues were observed significantly in captopril (P <0.05 or P < 0.01). Plasma BUN, Ang-II, TGF-β1 and PAI-1 in renal tissues decreased in the olive oil group significantly (P <0.05 or P < 0.01). PA (80, 40 and 20 mg/kg) lowered BP and plasmatic levels of Renin, Ang-II, TGF-β1 and PAI-1. Treatment with PA (40, 20 mg/kg) decreased levels of Cr, BUN and suppressed of activation of pro-fibrosis cytokines including TGF-β1 in kidney. There is no ameliorative change in the olive oil group and the captopril group (P > 0.05) while PA treatment alleviated renal tubular injury and produced dramatic collagen fibre area reductions in mesangial membrane, basement membrane, and renal interstitium obviously (P < 0.05 or P < 0.01). Treatment of SHR with PA-inhibited MFB activation and downregulated mRNA of α-SMA. Treatment with PA suppressed excessive production of the extracellular matrix (ECM) via decreasing Col I, III and FN, downregulating mRNA of tissue inhibitor of TIMP-1 along with upregulating mRNA of MMP-9. The expression of Col III and MMP-9 mRNA-reduced in the captopril group (P < 0.05). In addition, the expression of ERK1/2 and pERK1/2 also reduced in the captopril group significantly (P < 0.05 or P < 0.01). Treatment with PA (20 mg/kg) downregulated proteins expression of Raf-1, ERK1/2 and pERK1/2 and mRNA expression of Ras, Raf-1 and ERK1/2. Overall, PA restored normal BP, alleviated renal dysfunction and renal fibrosis, possibly by suppressing Ang II and TGF-β1-mediated Ras/Raf-1/ERK1/2 signalling pathway.

Empagliflozin increases kidney weight due to increased cell size in the proximal tubule S3 segment and the collecting duct.

The inhibition of renal SGLT2 glucose reabsorption has proven its therapeutic efficacy in chronic kidney disease. SGLT2 inhibitors (SGLTi) have been intensively studied in rodent models to identify the mechanisms of SGLT2i-mediated nephroprotection. So far, the overwhelming effects from clinical trials, could only partially be reproduced in rodent models of renal injury. However, a commonly disregarded observation from these studies, is the increase in kidney weight after SGLT2i administration. Increased kidney mass often relies on tubular growth in response to reabsorption overload during glomerular hyperfiltration. Since SGLT2i suppress hyperfiltration but concomitantly increase renal weight, it seems likely that SGLT2i have a growth promoting effect on the kidney itself, independent of GFR control. This study aimed to investigate the effect of SGLT2i on kidney growth in wildtype animals, to identify enlarged nephron segments and classify the size increase as hypertrophic/hyperplastic growth or cell swelling. SGLT2i empagliflozin increased kidney weight in wildtype mice by 13% compared to controls, while bodyweight and other organs were not affected. The enlarged nephron segments were identified as SGLT2-negative distal segments of proximal tubules and as collecting ducts by histological quantification of tubular cell area. In both segments protein/DNA ratio, a marker for hypertrophic growth, was increased by 6% and 12% respectively, while tubular nuclei number (hyperplasia) was unchanged by empagliflozin. SGLT2-inhibition in early proximal tubules induces a shift of NaCl resorption along the nephron causing compensatory NaCl and H2O reabsorption and presumably cell growth in downstream segments. Consistently, in collecting ducts of empagliflozin-treated mice, mRNA expression of the Na+-channel ENaC and the H2O-channels Aqp-2/Aqp-3 were increased. In addition, the hypoxia marker Hif1α was found increased in intercalated cells of the collecting duct together with evidence for increased proton secretion, as indicated by upregulation of carbonic anhydrases and acidified urine pH in empagliflozin-treated animals. In summary, these data show that SGLT2i induce cell enlargement by hypertrophic growth and possibly cell swelling in healthy kidneys, probably as a result of compensatory glucose, NaCl and H2O hyperreabsorption of SGLT2-negative segments. Particularly affected are the SGLT2-negative proximal tubules (S3) and the collecting duct, areas of low O2 availability.

Role of Bone Marrow Mesenchymal Stem Cells in p38MAPK Signaling Pathway and Extracellular Matrix Accumulation in Renal Tissue of Focal Segmental Glomerulosclerosis

BMSCs can effectively reduce the accumulation of extracellular matrix in renal tissues of rats with FSGS. This study intends to investigate the effect of BMSCs on extracellular matrix accumulation in renal tissues of rats with FSGS. 60 female mice aged 3 weeks were randomly assigned into control group, model group, transplantation group, positive control group and p38MAPK signaling pathway agonist group (agonist group) followed by analysis of renal histopathology, body weight, kidney weight and renal weight index of rats, expression of Col-IV, FN, MMP-9 protein and mRNA, as well as P38MAPK, P-CREB protein expression. The body weight, kidney weight and kidney weight index of rats in control group, transplant group and positive control group were significantly lower than those in model group and agonist group (P &lt; 0.05) without differences among control group, transplantation group, positive control group, model group and agonist group (P &gt; 0.05). COL-IV and FN protein and mRNA expression was higher in control group, transplantation group and positive control group, while MMP-9 expression was lower. However, agonist group and model group showed opposite profile of these proteins (P &lt; 0.05). The protein expressions of p38MAPK and P-CREB in control group and transplantation group were lower than those in model group, positive control group and agonist group (P &lt; 0.05) without significant difference among other groups (P &gt; 0.05). In conclusion, BMSCs can reduce the accumulation of extracellular matrix and glomerular sclerosis, thereby controlling FSGS progress.

CXCR4 inhibition suppresses Cd-induced renal oxidative stress, apoptosis, and fibrosis by inhibiting the TGF-β1/Smad pathway

This study aimed to investigate the role and mechanism of CXC chemokine receptor 4 (CXCR4) in cadmium (Cd)-induced renal injury. CXCR4 and TGF-β1/Smad pathway protein levels were detected by western blotting. Indicators related to renal function and oxidative stress factors were assessed and reactive oxygen species (ROS) level was evaluated by staining. TUNEL was used to measure apoptosis rate. PAS and Masson's trichrome staining were used to detect the level of renal fibrosis. The expression of Bcl-2, Bax, Cleaved-caspase 3, fibronectin, and collagen I proteins were detected by western blotting, immunohistochemistry, or immunofluorescence. The expression of CXCR4 was increased in a Cd-induced chronic renal injury model in rats. Si-CXCR4 decreased levels of TGF-β1, TGF-βR1, p-Smad2/Smad2, p-Smad3/Smad3, the renal weight index, urine protein, blood urea nitrogen, blood creatinine, and levels of MDA but raised the levels of SOD and GSH-Px. In addition, si-CXCR4 inhibited apoptosis in Cd-treated rats. CXCR4 inhibition alleviated fibrosis levels in Cd-treated rats. In Cd-treated cells, TGF-β attenuated the suppressive effect of CXCR4 inhibition on the TGF-β1/Smad pathway. TGF-β intervention increased MDA and ROS, and downregulated SOD and GSH-Px. TGF-β attenuated the inhibitory effect of CXCR4 on apoptosis and fibrosis. CXCR4 inhibition decreased levels of Cd-induced renal oxidative stress, apoptosis, and fibrosis by inhibiting the TGF-β1/Smad pathway.

Renal protective effect of ellipticine against streptozotocin induced diabetic nephropathy in rats via suppression of oxidative stress and inflammatory mediator.

Diabetes mellitus is a serious health problem worldwide, and diabetic nephropathy is the complication. The diabetic nephropathy considerably enhances the oxidative stress, glycation, lipid parameters and inflammatory reaction. Ellipticine has potent free radical scavenging and anti-inflammatory effect. In the current study, our objectives were to thoroughly examine the renal protective effects of ellipticine in a rat model of streptozotocin (STZ)-induced diabetic nephropathy (DN) and to elucidate the underlying mechanisms involved. For the induction of diabetic nephropathy, streptozotocin (50 mg/kg) was used, and rats were separated into groups and given varying doses of ellipticine (2.5, 5 and 7.5 mg/kg). The body weight, and renal weight were estimated. The inflammatory cytokines, renal biomarkers, inflammatory antioxidant, and urine parameters were estimated. Result showed that ellipticine considerably enhanced the body weight and reduced the renal tissue weight. Ellipticine treatment significantly (P < 0.001) repressed the level of blood urea nitrogen, serum creatinine, uric acid, blood glucose and altered the lipid parameters. Ellipticine significantly (P < 0.001) repressed the level of malonaldehyde and boosted the glutathione, catalase, superoxide dismutase, and glutathione peroxidase. Ellipticine treatment significantly (P < 0.001) reduced the inflammatory cytokines and inflammatory mediators. Ellipticine could be a renal protective drug via attenuating the inflammatory reaction, fibrosis and oxidative stress in streptozotocin induced rats.

Effect of Bining decoction on gouty nephropathy: a network pharmacology analysis and preliminary validation of gut microbiota in a mouse model

To use network pharmacology and gut microbiota sequencing to investigate the probable mechanism of Bining decoction (BN) in the treatment of gouty nephropathy (GN). Firstly, the mechanism of therapeutic effects of BN on GN were collected by integrating network pharmacology. Secondly, the treatment effects of BN against GN in 30 Institute of Cancer Research (ICR) mice were evaluated by performing biochemical tests [uric acid, blood urea nitrogen, and creatinine (UA, BUN, and Cr)] and evaluating the renal weight index. Finally, 16S rRNA sequencing was utilized for elucidating the therapeutical effect of BN in GN. The results of gut microbiota sequencing analysis showed the abundance of Faecalibaculum, Romboutsia, Bifidobacterium, Bacteroides, Odoribacter, Lachnospiraceae NK4A136 group, unclassified_f__Lachnospiraceae, Roseburia, norank_f__Lachnospiraceae, Lactobacillus, Dubosiella, norank_f__Muribaculaceae, and Turicibacter in the BN group had a significant changed between-group comparisons. Using a network pharmacology-related database, 413 active components of BN were identified, as well as 1,085 GN-associated targets. The 118 targets of disease targets and component targets were mapped, of which the top 10 genes were selected. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that 157 pathways were enriched, which was partially consistent with the metabolic pathways of gut microbiota sequencing analysis. Combining 16S rRNA gene sequencing and network pharmacology analysis, similar signaling pathways were followed: "Pathways in cancer" and "Adipocytokine signaling pathway". The results reveal that BN increases the abundance of Turicibacter, regulates the expression of JAK2 in the JAK/STAT pathway, increases the beneficial bacteria Turicibacter associated with intestinal butyric acid, which could enhance the intestinal barrier, and exert anti-inflammatory effects.

Effects of Ziyin Qianyang Formula on Renal Fibrosis through the TGF-β1/Smads Signaling Pathway in Spontaneously Hypertensive Rats.

The aim of the study is to explore the effects and mechanisms of action of Ziyin Qianyang Formula (ZYQYF) on renal fibrosis in spontaneously hypertensive rats (SHRs). Forty SHRs were randomly divided into a model group, Ziyin Qianyang Formula regular-dose and high-dose groups (ZYQYF-R, 20 g/kg; ZYQYF-H, 40 g/kg), and a western medicine group (enalapril 10 mg/kg), and 10 Sprague-Dawley rats were selected as the normal group. The rats received continuous gavage administration for 6 weeks and systolic blood pressure (SBP) measurements were obtained every fortnight. The serum levels of urea, serum creatinine (sCr), and uric acid (UA) were measured; the pathological morphology and collagen content of the kidneys were observed by hematoxylin-eosin (HE) and Masson staining; and the serum Ang II level was measured by an enzyme-linked immunosorbent assay (ELISA). Transforming growth factor (TGF)-β1, Smad-2, Smad-3, and Smad-7 protein and mRNA expressions in kidney tissues was evaluated by western blotting and reverse transcription-polymerase chain reaction. The ZYQYF-H group showed significantly a lower renal weight and renal weight/body weight than the model group. The enalapril and ZYQYF-H groups showed significantly lower SBP than other groups after 6 weeks of administration. The ZYQYF-H group showed better improvement than the ZYQYF-R and enalapril groups in glomerular and tubular morphology and better reductions in inflammatory cell infiltration and collagen volumetric fraction. The ZYQYF-H group also showed better reductions in serum UA and Ang II levels; collagen-I, collagen-III, and p-Smad2/Smad-2 protein expression; and Smad-2 mRNA expression and a better increase in Smad-7 protein and mRNA expression than the enalapril group. Besides, the degree of renal function and fibrosis improvement was positively correlated with the dose of ZYQYF. ZYQYF can significantly reduce SHR blood pressure, protect renal function and structure, and improve renal fibrosis by regulating Smad proteins through TGF-β1.

Ameliorating Effects of Silymarin-Loaded PLGA on Acetaminophen-Induced Nephrotoxicity in Mice

Background: Silymarin (SM) has beneficial effects against numerous different types of toxicants. However, the low bioavailability of SM has limited its therapeutic effects. Objectives: This study investigated the toxic effect of nanostructured SM (NSM) in poly(lactic-co-glycolic acid) (PLGA) nanoparticles on nephrotoxicity induced by acetaminophen (APAP) in mice. Methods: The encapsulation of SM in PLGA was performed by the solvent evaporation method. A total of 48 NMRI mice were used in this experimental study. The mice were pretreated with SM or NSM (5 mg/kg) for 7 days, and APAP (300 mg/kg) was administrated on the 6th day. The serum levels of blood urea nitrogen, creatinine, and uric acid were measured. Histological assessment and messenger ribonucleic acid expression of BAX and BCL-2 genes were also carried out. Results: The APAP destroyed the structure of the renal tissue and significantly reduced renal weight and glomerulus diameters (P &lt; 0.01). The APAP also caused a significant increase in the serum levels of biochemical markers (P &lt; 0.001) and expression of the BAX/BCL-2 ratio in the renal tissue (P &lt; 0.001). The NSM could improve the renal structure and significantly increase renal weight and glomerulus in the APAP-intoxicated mice. The NSM significantly reduced the level of the biochemical tests and the BAX/BCL-2 ratio in the APAP-treated group (P &lt; 0.01). Conclusions: The obtained data indicate that PLGA effectively enhances the nephroprotective effects of SM on nephrotoxicity induced by APAP.

Lycoperoside H protects against diabetic nephropathy via alteration of gut microbiota and inflammation.

It is well known that hyperglycemia leads to the progression and expansion of various micro and macrovascular disease such as diabetic nephropathy (DN). Lycoperoside H (LH) alkaloidal saponin exhibited the antidiabetic effect, but its DN effect is unclear. In this experimental study, we scrutinized the renal protective effect of LH against the streptozotocin (STZ)-induced DN in rats and explore the underlying mechanism. Sprague-Dawleyrats were used in this experimental study and an intraperitoneal injection of STZ (45 mg/kg) was used for the induction of diabetes, rats received the oral administration of LH (20 mg/kg). The blood glucose level, body weight, organ weight (renal and pancreas), and biochemical parameters were estimated. We also scrutinized the effect of LH to enhance intestinal barrier function and suppress inflammation and intestinal permeability. LH significantly (p < 0.001) decreased the glucose level and enhanced the body weight with a reduction of renal weight and boost the pancreas weight. LH significantly (p < 0.001) enhanced the creatinine level and decreased the albumin level, urine volume, urinary albumin excretion rate, and urinary albumin creatinine ratio in the urine. It also suppressed the renal parameters, such as creatinine, blood urea nitrogen, and urea. LH significantly (p < 0.001) altered the level of lipid and antioxidant parameters. LH treatment significantly (p < 0.001) suppressed the cytokines and inflammatory parameters. LH considerably enhanced the Ruminococcaceae, Blautia, and suppressed the abundance of Bifidobacterium, Clostridium, and Turicibacter. It reduced the F/B ratio along with alteration of community abundance of Firmicutes, Actinobacteria, Proteobacteria, Tenericutes, other bacteria, and Bacteroidetes. The current result suggests that LH suppressed the diabetic nephropathological condition via alteration of gut microbiota and inflammation.

Nephro-protective effect of Daphnetin in hyperoxaluria-induced rat renal injury via alterations of the gut microbiota.

It is well proved that hyperoxaluria induces the renal injury and finally causes the end stage kidney disease. Daphnetin (coumarin derivative) already confirmed renal protective effect in renal model, but hyperoxaluria protective effect still unexplore. The objective of this research was to scrutinize the renal protective effect of daphnetin against ethylene glycol (GC)-induced hyperoxaluria via altering the gut microbiota. GC (1% v/v) was used for the induction of hyperoxaluria in the rats and the rats were received the oral administration of daphnetin (5, 10 and 15 mg/kg). The body and renal weight were assessed. Urine, renal, inflammatory cytokines, antioxidant, inflammatory parameters, and gut microbiota were appraised. Daphnetin effectually improved the body weight and reduced the renal weight. Its also remarkably boosted the magnesium, calcium, citrate level and suppressed the level of uric acid and oxalate formation. Daphnetin significantly (p < .001) ameliorate the level of urinary kidney injury molecule 1 (KIM-1), blood urea nitrogen (BUN), urea, serum creatinine (Scr), neutrophil gelatinase-associated lipocalin (NGAL) and uric acid along with inflammatory cytokines and inflammatory mediators. Daphnetin considerably repressed the malonaldehyde (MDA) level, protein carbonyl and improved the level of glutathione reductase (GR), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT). Daphnetin treatment considerably altered the microbial composition of different bacteria at phylum, genus and family level. Daphnetin significantly suppressed the Firmicutes relative abundance and boosted the Bacteroidetes relative abundance. Our result clearly indicated that daphnetin remarkably ameliorates the GC induced hyperoxaluria in rats via altering the oxidative stress, inflammatory reaction and gut microbiota. PRACTICAL APPLICATION: Nephrotoxicity is a serious health disease worldwide. We induce the renal toxicity in the experimental rats using the ethylene glycol and scrutinized the renal protective effect of daphnetin. Daphnetin considerably suppress the renal, urine parameters. For estimation the underlying mechanism, we estimated the gut microbiota in all group rats. Daphnetin remarkably altered the level of gut microbiota and suggesting the renal protective effect.

Effects of losartan on bladder dysfunction due to aging-related severe hypertension in rats

Aging is a major risk factor for bladder dysfunction. Anti-hypertensive drugs, angiotensin II type 1 receptor blockers (ARBs), are reported to ameliorate lower urinary tract dysfunction in rodent models and humans. We aimed to examine the preventive effect of an ARB, losartan, against bladder dysfunction due to aging-related severe hypertension. Male spontaneously hypertensive rats (SHRs) (36-week-old) were administered losartan (0, 3, or 10 mg/kg, p.o.) for 18 weeks. Age-matched, vehicle-treated Wistar Kyoto rats (WKYs) were used as controls. After the treatments, bladder and renal weight, mean blood pressure, and voiding parameters were measured. Additionally, detrusor thickness and bladder arterial wall thickness were evaluated using hematoxylin and eosin staining. Renal morphology was also assessed using periodic acid-Schiff staining. Compared to WKYs, SHRs demonstrated significantly higher bladder weight/body weight ratio (BBR), renal weight/body weight ratio, mean blood pressure, detrusor thickness, bladder arterial wall thickness, urine output, water intake, post-voiding residual urine volume, bladder capacity, intercontraction interval, and rate of glomerular and tubular injury and a lower urine osmolality. A low dose of losartan decreased the urine output, post-voiding residual urine volume, and bladder capacity in SHRs but not mean blood pressure in SHRs. A high dose of losartan decreased the BBR, mean blood pressure, detrusor thickness, bladder arterial wall thickness, post-voiding residual urine volume, bladder capacity, intercontraction interval, and glomerular and tubular injury in SHRs. Losartan inhibits bladder dysfunction in aged SHRs. The ARB losartan might be a preventive drug for bladder dysfunction due to aging-related severe hypertension.

Pueraria montana (Kudzu vine) Ameliorate the Inflammation and Oxidative Stress against Fe-NTA Induced Renal Cancer.

Renal tissue plays a crucial function in maintaining homeostasis, making it vulnerable to xenobiotic toxicity. Pueraria montana has more beneficial potential against the various diseases and has long history used as a traditional Chinese medicine. But its effect against the renal cancer not scrutinize. The goal of this study is to see if Pueraria montana can protect rats from developing kidney tumors caused by diethylnitrosamine (DEN) and ferric nitrite (Fe-NTA). Wistar rats was selected for the current study and DEN (use as an inducer) and Fe-NTA (promoter) for induction the renal cancer. For 22 weeks, the rats were given orally Pueraria montana (12.5, 25, and 50 mg/kg) treatment. At regular intervals, the body weight and food intake were calculated. The rats were macroscopically evaluated for identification of cancer in the renal tissue. The renal tumor makers, renal parameters, antioxidant enzymes, phase I and II enzymes, inflammatory cytokines and mediators were estimated at end of the experimental study. Pueraria montana treated rats displayed the suppression of renal tumors, incidence of the tumors along with suppression of tumor percentage. Pueraria montana treated rats significantly (p < 0.001) increased body weight and suppressed the renal weight and food intake. It also reduced the level of renal tumor marker ornithine decarboxylase (ODC) and [3H] thymidine incorporation along with suppression of renal parameter such as uric acid, blood urea nitrogen (BUN), urea and creatinine. Pueraria montana treatment significantly (p < 0.001) altered the level of phase enzymes and antioxidant. Pueraria montana treatment significantly (p < 0.001) repressed the level of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and improved the level of interleukin-10 (IL-10). Pueraria montana treatment suppressed the level of prostaglandin (PGE2), cyclooxygenase-2 (COX-2), nuclear kappa B factor (NF-κB) and transforming growth factor beta 1 (TGF-β1). Pueraria montana suppressed the inflammatory necrosis, size the bowman capsules in the renal histopathology. Pueraria montana exhibited the chemoprotective effect via dual mechanism such as suppression of inflammatory reaction and oxidative stress.

Зміни нефрогенезу ембріонів щура при інтоксикації солями кадмію вагітних самиць

The purpose of the experimental study was to determine morphogenetic disorders of embryonic and fetal kidney development in chronic intragastric exposure to cadmium salts (cadmium chloride, cadmium citrate) in pregnant females. Materials and methods. Low doses of cadmium salts were selected for the study, which can be compared with the actual concentration of cadmium in the daily diets of women, including pregnant women, in industrial regions. In the experiment, female rats with a given gestational age were divided into groups as follows: Group 1 – control (number of females – n = 16, of which 8 left the experiment on the 13th day of pregnancy, and 8 on the 20th; the number of embryos – n13 = 76; n20 = 77); Group 2 – administration of cadmium chloride at a dose of 1.0 mg/kg body weight of the female (number of females – n = 16; number of embryos – n13 = 65; n20 = 62); Group 3 – administration of cadmium citrate at a dose of 1.0 mg/kg body weight of the female (number of females – n = 16; number of embryos – n13 = 69; n20 = 70). Results and discussion. New quantitative data on the effect of cadmium salts were obtained on the thickness of the cortical and cerebral layers of the kidneys, the diameter and area of the cavity of the nephron capsule in the prenatal period of development in chronic female intoxication. On the 13th day, the effect of cadmium salts on the development of embryonic kidneys was multidirectional: the effect of cadmium chloride led to an increase in the thickness of the mesonephros and mesonephric duct, and the effect of cadmium citrate reduced the studied parameters. On the 20th day of rat embryogenesis in the group exposed to cadmium chloride, the renal weights increased, and when exposed to cadmium citrate, the weight of the kidneys decreased significantly (p˂0.05) both in comparison with control values and in the group exposed to cadmium chloride. On the 20th day of development, in order to exclude an error in estimating the dynamics of changes in the weight of embryo mass and kidney mass, the nephrofetal index was calculated, i.e. the ratio of wet kidney mass to wet weight of fixed fetus. Histological parameters of nephron diameters were also compared. Conclusion. Cadmium citrate has been shown for the first time to be less non-photoxic than cadmium chloride. Calculation of the area of the cavity of the nephron capsule by the spline contour method showed a 2.6-fold decrease in the average area of the capsule cavity in the group exposed to cadmium chloride relative to the control mean values, indicating a violation of nephrogenesis. When exposed to cadmium citrate, there was also a decrease in the area of the cavity of the nephron capsule by 1.8 times, which indicates a lower level of nephrotoxic cadmium citrate compared to cadmium chloride, despite the identity of the dose of exposure

Morphofunctional study on the effects of passive smoking in kidneys of rats.

ABSTRACTObjective To analyze whether passive inhalation of cigarette smoke causes morphological, structural, and functional changes in kidneys of rats.Methods Wistar rats, aged eight weeks, weighing on average 260g, were divided into Control Group and Smoking Group. Each group was subdivided into four groups of ten animals for morphofunctional analysis, in a period of seven and 28 days. The Smoking Group was exposed to smoke of 40 cigarettes per day, at certain times and in automated equipment for cigarette burning, called smoking machine (SM-MC-01). After the exposure period, urine and blood samples were collected for the functional analyses, and the kidneys were dissected and submitted to histological procedures for morphoquantitative analyses.Results After exposure of animals of the Smoking Group, the following were observed: lower weight gain; lower water and feed intake; decreased renal weight, diameter, and volume; reduction in cortical thickness and glomerular volume density; decrease in glomerular and capsular diameter; increase in mesangial density; decreased urine volume; increased levels of glucose, serum creatinine and microalbuminuria; decreased urinary creatinine levels and creatinine clearance rate.Conclusion Passive smoking negatively influences renal morphology and glomerular filtration rate, with effects similar to those described in the literature regarding active smoking.

Associations between obesity, weight change and decreased renal function in Korean type 2 diabetic patients: a longitudinal follow-up study

BackgroundWe aimed to examine the associations between the risk of decreased renal function, obesity, and weight changes in Korean type 2 diabetic patients with normal renal function.MethodsType 2 diabetic patients (n = 1060) who visited the diabetic clinic at Soonchunhyang University Bucheon Hospital between 2001 and 2007 with follow up surveys completed in 2016 to 2017 were recruited into the study. Decreased renal function was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2. Weight change was calculated between baseline and each follow-up survey. Multivariate analysis was used to evaluate the longitudinal association of baseline obesity and weight changes with the risk of decreased renal function.ResultsThis study revealed that baseline obesity was associated with the risk of decreased renal function after adjusting for clinical variables in type 2 diabetic patients (odds ratio [OR] 1.40; 95% confidence intervals [CI] 1.08–2.04; p = 0.025). Follow-up (mean = 12 years) revealed that weight gain > 10% was associated with the risk of decreased renal function after adjusting for clinical variables in type 2 diabetic patients with normal renal function at baseline (OR 1.43; CI 1.11–2.00; p = 0.016). Weight loss was not associated with the risk of decreased renal function in type 2 diabetic patients with normal renal function at baseline.ConclusionsBaseline obesity was associated with the increased risk of decreased renal function in Korean type 2 diabetic patients with normal renal function. Weight gain > 10% independently predicted the risk of decreased renal function. Large prospective studies are needed to clarify causal associations between obesity, weight change, and decreased renal function in patients with type 2 diabetes.