Renoprotective effects of long-term oral nicotine in a rat model of spontaneous proteinuria

2012 ◽  
Vol 302 (7) ◽  
pp. F895-F904 ◽  
Author(s):  
Pramod K. Agarwal ◽  
Jacob van den Born ◽  
Harry van Goor ◽  
Gerjan Navis ◽  
Rijk O. B. Gans ◽  
...  
Keyword(s):  
Rat Model ◽  
Structural Damage ◽  
Kidney Diseases ◽  
Blood Pressure Reduction ◽  
Renal Diseases ◽  
Control Group ◽  
Renal Inflammation ◽  
Anti Inflammatory ◽  
Oral Nicotine

Many proteinuric renal conditions are accompanied by renal inflammation. Nicotine is known to have anti-inflammatory properties and is used in oral form to help subjects quit smoking. A potential anti-inflammatory role of nicotine in proteinuric renal diseases has not been investigated to date. We therefore evaluated the effects of oral nicotine in a rat model of proteinuria-induced renal inflammation. We used a well-established model of adult (24 wk of age) male Munich-Wistar-Frömter rats. Animals were given three different physiological doses of nicotine in drinking water for 28 wk until 52 wk of age (long term). A group without nicotine served as a parallel control. At 52 wk of age, the control group had a 2.1 times reduction in creatinine clearance, 3.2 times increase in urinary protein excretion, an increased focal glomerulosclerosis (FGS) score, increased glomerular desmin deposition, decreased glomerular podocin, and a higher accumulation of macrophages and myofibroblasts compared with 24-wk-old animals. Oral treatment with nicotine dose dependently preserved renal function and halted proteinuria progression, which were independent of blood pressure reduction. It also reduced FGS, desmin deposition, podocin loss, and density of renal macrophages and myofibroblasts. Nicotine also reduced the level of gene expression of the renal inflammatory markers monocyte chemoattractant protein and vascular cell adhesion molecule-1. In conclusion, long-term oral nicotine preserved kidney function, reduced proteinuria, reduced renal inflammation, and protected progression of renal structural damage in a rat model of proteinuria. We further suggest evaluating nicotine as a potential additional therapeutic option for treating proteinuric kidney diseases.

Catheter Patency and Peritoneal Morphology and Function in a Rat Model of Citrate-Buffered Peritoneal Dialysis

2010 ◽  
Vol 30 (6) ◽  
pp. 602-610 ◽  
Author(s):  
Nicola Cavallini ◽  
Magnus Braide
Keyword(s):  
Peritoneal Dialysis ◽  
Rat Model ◽  
Fluid Transport ◽  
Separate Experiment ◽  
Control Group ◽  
Vascular Density ◽  
Long Term Effects ◽  
Catheter Patency ◽  
Peritoneal Morphology

BackgroundSingle-dwell studies in rats and humans have shown that supplementing citrate for lactate in peritoneal dialysis (PD) fluids improves ultrafiltration (UF).MethodsThe long-term effects of citrate-substituted PD fluids on PD catheter patency, UF, and peritoneal morphology were evaluated in a rat model over 5 weeks of daily PD fluid exposure. A standard 2.5% glucose 40 mmol/L lactate PD fluid and a corresponding 10/30 mmol/L citrate/lactate PD fluid were compared. In a control group, rats with catheters received no PD fluid.ResultsThe average patency time (% of 36 days) of silicone rubber PD catheters was significantly longer in the citrate PD group (98.8% ± 1.2%) and the control group (100% ± 0%) compared to the lactate PD group (54.7% ± 9.5%). In a separate experiment, heparin-coated polyurethane catheters were used to study peritoneal morphology and fluid transport. The citrate group had a higher net UF than the lactate group at the beginning and at the end of the 5 weeks. During the experiment, both fluid-treated groups suffered from UF loss; the control group showed the highest net UF at the end of the 5 weeks. Peritoneal vascular density and submesothelial thickness, indicators of angiogenesis and fibrosis, were not significantly different among the groups. Fibrosis was significantly negatively correlated to osmotic UF.ConclusionA positive acute effect of citrate on UF was confirmed and conserved over time. Citrate PD strongly improved PD catheter patency time compared with lactate. Both citrate PD and lactate PD induced negative long-term effects on UF compared with control animals.

Inhibition of Necroptosis Attenuates Kidney Inflammation and Interstitial Fibrosis Induced By Unilateral Ureteral Obstruction

2017 ◽  
Vol 46 (2) ◽  
pp. 131-138 ◽  
Author(s):  
Xia Xiao ◽  
Chunyang Du ◽  
Zhe Yan ◽  
Yonghong Shi ◽  
Huijun Duan ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Potential Role ◽  
Interstitial Fibrosis ◽  
Kidney Diseases ◽  
Specific Inhibitor ◽  
Unilateral Ureteral Obstruction ◽  
Renal Diseases ◽  
Renal Interstitial Fibrosis ◽  
Renal Inflammation ◽  
Renal Histology

Background: Inflammation plays a crucial role in renal interstitial fibrosis, the pathway of chronic kidney diseases. Necroptosis is a novel form of regulated cell death, which plays a potential role in inflammation and renal diseases. The small molecule necrostatin-1 (Nec-1) is a specific inhibitor of necroptosis. This study was aimed at determining the role of necroptosis, RIP1/RIP3/mixed lineage kinase domain-like (MLKL) signaling pathway, in renal inflammation and interstitial fibrosis related to primitive tubulointerstitial injury. It was also aimed at evaluating the effect of Nec-1 in renal fibrosis induced by unilateral ureteral obstruction (UUO). Methods: Renal histology, immunohistochemistry, western blot, and real-time polymerase chain reaction were performed using UUO C57BL/6J mice model. Moreover, we tested whether Nec-1 was renal-protective in the interstitial fibrosis kidney. Mice were exposed to UUO and injected intraperitoneal with Nec-1 or vehicle. Results: The levels of RIP1/RIP3/MLKL protein and mRNA were increased in the obstructed kidneys 7 days after UUO; this was accompanied by changes in renal pathological lesions. Renal histological examination showed lesser renal damage in Nec-1-treated UUO mice. Renal inflammation, assessed by tumor necrosis factor-α, interleukin-1β, and monocyte chemotactic protein-1 was markedly attenuated by Nec-1. Furthermore, Nec-1 treatment also significantly reduced TGF-β and α-smooth muscle actin, indicating lesser renal interstitial fibrosis. Conclusion: These findings suggest that the participation of necroptosis in UUO is partly demonstrated. And necroptosis inhibition may have a potential role in the treatment of diseases with increased inflammatory response and interstitial fibrosis in renal.

scholarly journals Ethanolic Extract of Centella asiatica Treatment in the Early Stage of Hyperglycemia Condition Inhibits Glomerular Injury and Vascular Remodeling in Diabetic Rat Model

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Wiwit A. W. Setyaningsih ◽  
Nur Arfian ◽  
Akbar S. Fitriawan ◽  
Ratih Yuniartha ◽  
Dwi C. R. Sari
Keyword(s):  
Diabetes Mellitus ◽  
Vascular Injury ◽  
Rat Model ◽  
Vascular Remodeling ◽  
Kidney Diseases ◽  
Early Stage ◽  
Vascular Dysfunction ◽  
Centella Asiatica ◽  
Control Group ◽  
Glomerular Injury

Background. Diabetes mellitus (DM) is marked by oxidative stress, inflammation, and vascular dysfunction that caused diabetic nephropathy that resulted in end-stage renal disease (ESRD). Vascular dysfunction is characterized by an imbalance in vasoconstrictor and vasodilator agents which underlies the mechanism of vascular injury in DM. Additionally, diminished podocytes correlate with the severity of kidney injury. Podocyturia often precedes proteinuria in several kidney diseases, including diabetic kidney disease. Centella asiatica (CeA) is known as an anti-inflammatory and antioxidant and has neuroprotective effects. This research aimed to investigate the potential effect of CeA to inhibit glomerular injury and vascular remodeling in DM. Methods. The DM rat model was induced through intraperitoneal injection of streptozotocin 60 mg/kg body weight (BW), and then rats were divided into 1-month DM (DM1, n = 5), 2-month DM (DM2, n = 5), early DM concurrent with CeA treatment for 2 months (DMC2, n = 5), and 1-month DM treated with CeA for 1-month (DM1C1, n = 5). The CeA (400 mg/kg BW) was given daily via oral gavage. The control group (Control, n = 5) was maintained for 2 months. Finally, rats were euthanized and kidneys were harvested to assess vascular remodeling using Sirius Red staining and the mRNA expression of superoxide dismutase, podocytes marker, ACE2, eNOS, and ppET-1 using RT-PCR. Results. The DM groups demonstrated significant elevation of glucose level, glomerulosclerosis, and proteinuria. A significant reduction of SOD1 and SOD3 promotes the downregulation of nephrin and upregulation of TRPC6 mRNA expressions in rat glomerular kidney. Besides, this condition enhanced ppET-1 and inhibited eNOS and ACE2 mRNA expressions that lead to the development of vascular remodeling marked by an increase of wall thickness, and lumen wall area ratio (LWAR). Treatment of CeA, especially the DMC2 group, attenuated glomerular injury and showed the reversal of induced conditions. Conclusions. Centella asiatica treatment at the early stage of diabetes mellitus ameliorates glomerulosclerosis and vascular injury via increasing antioxidant enzymes.

Novel anti-inflammatory actions of amlodipine in a rat model of arteriosclerosis induced by long-term inhibition of nitric oxide synthesis

2004 ◽  
Vol 286 (2) ◽  
pp. H768-H774 ◽  
Author(s):  
Chu Kataoka ◽  
Kensuke Egashira ◽  
Minako Ishibashi ◽  
Shujiro Inoue ◽  
Weihua Ni ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Rat Model ◽  
Vascular Inflammation ◽  
Monocyte Chemoattractant Protein 1 ◽  
Beneficial Effects ◽  
Pressure Lowering ◽  
Anti Inflammatory ◽  
Synthase Inhibitor

Amlodipine (a new class of calcium channel antagonist) has been shown to limit the progression of arteriosclerosis and decrease the incidence of cardiovascular events. The mechanisms underlying the beneficial effects of amlodipine, however, remain unclear. Therefore, we hypothesized that amlodipine attenuates the development of arteriosclerosis through the inhibition of inflammation in vivo. Long-term inhibition of nitric oxide (NO) by administration of a NO synthase inhibitor, Nω-nitro-l-arginine methyl ester (l-NAME), to rats induces coronary vascular inflammation [monocyte infiltration, monocyte chemoattractant protein-1 (MCP-1) expression, increased activity of angiotensin-converting enzyme (ACE)], and arteriosclerosis. Here, we used the rat model to investigate the anti-inflammatory effects of amlodipine in vivo. Treatment with amlodipine markedly inhibited the l-NAME-induced increase in vascular inflammation, oxidative stress, and local ACE and Rho activity and prevented arteriosclerosis. Interestingly, amlodipine prevented the l-NAME-induced increase in MCP-1 receptor CCR2 expression in circulating monocytes. Amlodipine markedly attenuated the high mortality rate at 8 wk of treatment. These data suggest that amlodipine attenuated arteriosclerosis through inhibiting inflammatory disorders in the rat model of long-term inhibition of NO synthesis. The anti-inflammatory effects of amlodipine seem to be mediated not only by the inhibition of local factors such as MCP-1 but also by the decrease in CCR2 in circulating monocytes. Inhibition of the MCP-1 to CCR2 pathway may represent novel anti-inflammatory actions of amlodipine beyond blood pressure lowering.

scholarly journals Liraglutide exhibits anti-inflammatory activity through the activation of the PKA/CREB pathway

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Li Wang ◽  
Linjie Feng ◽  
Jingyu Zhang
Keyword(s):  
Rat Model ◽  
Inflammatory Activity ◽  
Control Group ◽  
Anti Inflammatory ◽  
The Sacrifice ◽  
Creb Pathway

Abstract Qihong Que and colleagues found that liraglutide exhibited anti-inflammatory activity through the activation of the PKA/CREB pathway in an OA rat model. We believe there was a flaw in this research. In their first experiment, the sacrifice time of the 10 rats in the control group has not been stated. And when the rats in the OA-1, OA-5, OA-10, OA-20 and OA-28 groups were sacrificed, they were in different weeks of age. If the rats in the control group were compared to the rats in the OA-1, OA-5, OA-10, OA-20 and OA-28 groups respectively, the results may be biased due to differences in the week age of the rats. We believe that addressing this issue could further increase the value of their study.

scholarly journals Implications of Statin Use on Vasopressor Therapy in the Setting of Septic Shock

2018 ◽  
Vol 53 (3) ◽  
pp. 152-156
Author(s):  
Chelsey M. McPheeters ◽  
Jennifer A. Wiedmar ◽  
Christina M. Pinkston ◽  
Kyle A. Weant
Keyword(s):  
Septic Shock ◽  
Inflammatory Responses ◽  
Control Group ◽  
Vasopressor Therapy ◽  
Statin Group ◽  
Improved Outcomes ◽  
Anti Inflammatory ◽  
Time Of Admission ◽  
Statin Use

Background: Pleiotropic anti-inflammatory and immunomodulatory effects of statins have been associated with improved outcomes in the critically ill population. Objective: To evaluate the implications of prior statin use on the duration of vasopressor therapy in the setting of septic shock. Methods: This was a retrospective, multicenter study of adult patients who were diagnosed with septic shock. Patients were included if they were treated with any vasopressor for greater than 6 hours from the time of admission. The primary outcome was to compare the duration of vasopressor therapy in patients with septic shock with and without previous statin exposure. Results: A total of 88 statin-exposed cases and 205 unexposed controls were included in the analysis. Despite 92% of statin-exposed patients being reinitiated on therapy within 24 hours, the duration of vasopressors did not differ between groups (44 hours, statin group vs 53 hours, control group, P = .51). There were also no mortality differences between the statin group and the controls (40% vs 47%, P = .27). Conclusions: Long-term statin exposure does not impact the duration of vasopressor therapy in septic shock. The lack of differences in clinical outcomes supports the concept that sepsis involves pro- and anti-inflammatory pathways as well as other nonimmunologic pathways. Results lend further credence to the recent conceptualization of sepsis, with complications leading to organ dysfunction caused not primarily due to inflammatory responses but by a dysregulated response to infection.

scholarly journals Use of Intranasal Insulin as Neuroprotection From Hyperglycemia in Rat Model of Extremely Preterm Infants

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A444-A444
Author(s):  
Lauren McClure Yauch ◽  
Kathleen Ennis ◽  
Ivan Tkac ◽  
Raghavendra Rao
Keyword(s):  
Preterm Infants ◽  
Neuronal Activity ◽  
Rat Model ◽  
Control Group ◽  
Intranasal Insulin ◽  
Long Term Effects ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Neurochemical Profile

Abstract Background: Hyperglycemia is common in extremely preterm infants (EPI) and is a risk factor for increased mortality and morbidity, including abnormal neurodevelopment. Hippocampus-mediated cognitive deficits are common in this population. In a rat model of insulinopenic hyperglycemia, abnormal neurochemistry in the hippocampus was found, with lactate, glutamate (Glu):glutamine (Gln) ratio lower and Phosphorylated Creatinine (PCr):Creatinine (Cr) higher. Intranasal insulin has been shown to improve cognitive function in animal models of Alzheimer’s disease and type 2 diabetes mellitus, as well as in adult human studies of Alzheimer’s disease. No study has previous investigated the use of intranasal insulin on preventing the long-term effects of hyperglycemia in the EPI population. Objective: To determine whether administration of intranasal insulin during early postnatal days would negate the effects of hyperglycemia on the developing hippocampus in neonatal rat model of streptozotocin (STZ)-induced hyperglycemia. Design/Methods: STZ (80mg/kg IP) was injected on postnatal day (P) 2, and littermates in the control group were injected with an equivalent volume of citrate buffer. STZ pups were randomized to intranasal insulin, 3U twice daily from P3-P6 (STZ + INS) or left untreated (STZ). Neurochemical profile (consisting of 20 metabolites, PCr:Cr and Glu:Gln ratios) of the hippocampus was evaluated using ultra-high-field (9.4 T) magnetic resonance spectroscopy (MRS) on P7 (acute effects) and P56 (long-term effects) compared with the control group (CON)(N=6/group). Results: Mean glucose values from P3-P6 were higher in STZ groups (STZ = 279.0 +/- 132.2 mg/dL, STZ+INS = 274.4 +/- 89.5 mg/dL, CONT = 128.4 +/- 15.1 mg/dL). The neurochemical profile was different at both P7 and P56. On P7, compared with the control, the taurine (Tau) was higher in the STZ groups (p = 0.007. At P56, PCr:Cr was higher in the STZ group compared to CONT and STZ+INS groups (p = 0.04). No difference noted between the STZ+INS and CONT groups. No other metabolites were altered. Conclusion: Neonatal hyperglycemia alters the acute and long-term neurochemical profile in the hippocampus of developing rats. The increase in PCr:Cr ratio in the STZ group indicates lower demand for ATP and PCr, secondary to decreased neuronal activity, which has been demonstrated in previous studies. PCr:Cr ratio of the STZ+INS group was no different than control, indicating that intranasal insulin reverses the negative effect on neuronal activity caused by neonatal hyperglycemia.

scholarly journals The effects of steroidal and non-steroidal anti-inflammatory drugs on tracheal wound healing in an experimental rat model

2020 ◽  
Vol 30 (4) ◽  
pp. 646-651
Author(s):  
Elif Duman ◽  
Kenan Can Ceylan ◽  
Deniz Akpınar ◽  
Nur Yücel ◽  
Şaban Ünsal ◽  
...  
Keyword(s):  
Wound Healing ◽  
Rat Model ◽  
Control Group ◽  
Albino Rats ◽  
Nsaid Group ◽  
Steroid Group ◽  
Histological Characteristics ◽  
Experimental Rat Model ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Abstract OBJECTIVES The effect of non-steroidal anti-inflammatory drugs (NSAID), mostly used for postoperative analgesic purposes for wound healing, is still a matter of debate. Our goal was to evaluate the effects of the most widely used NSAID and corticosteroids after surgical operations on tracheal wound healing in an experimental rat model. METHODS Thirty-nine male Wistar albino rats were included in this study. Tracheotomy was performed in 32 rats; then they were divided into 3 groups. After the first day, the animals in group 1 were treated with an NSAID (diclofenac 10 mg/kg/day) (NSAID, n = 12) for 7 days; the animals in group 2 were treated with a corticosteroid (dexamethasone, 2 × 0.1 mg/kg/day) (steroid, n = 10) for 7 days; the animals in group 3 (control, n = 10) were not given any medications. For a fourth group (histological control, n = 7), in order to evaluate normal morphological and histological characteristics, neither surgery nor medication was used. Five rats were eliminated from the study (2 rats in the NSAID group died and 3 rats in the steroid group developed local wound infections). The drop-out rate was 12.8%. Histological characteristics, inflammation, fibrosis, necrosis, neochondrogenesis, neovascularization and epithelization were evaluated in 34 rats. Non-parametric tests were used for statistical analysis. RESULTS Inflammation, vascularization and number of fibroblasts and chondrocytes were significantly higher in the control group than in the histological control group. There was some reduction in all parameters except vascularization in the NSAID group (P > 0.05). When the steroid group was compared to the NSAID group, inflammation (P < 0.05), vascularization and number of chondrocytes (P > 0.05) were more suppressed in the steroid group. The number of fibroblasts increased in the steroid group (P > 0.05). CONCLUSIONS Steroids and NSAID may have negative effects on tracheal wound healing, probably by suppressing inflammation and fibroblast proliferation. NSAID was mostly used postoperatively for analgesic purposes and should be avoided.

scholarly journals A New Non-Uremic Rat Model of Long-Term Peritoneal Dialysis

2011 ◽  
pp. 157-164 ◽  
Author(s):  
Y.-M. PENG ◽  
Z.-J. SHU ◽  
L. XIAO ◽  
L. SUN ◽  
W.-B. TANG ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Rat Model ◽  
Clinical Aspects ◽  
Control Group ◽  
Sham Operation ◽  
Significant Difference ◽  
Group 2 ◽  
Group 1 ◽  
Glucose Group

Together with the development of peritoneal dialysis (PD), appropriate animal models play an important role in the investigation of physiological, pathophysiological and clinical aspects of PD. However, there is still not an ideal experimental PD animal model. In this study, 45 Sprague-Dawley rats were divided into three groups. Group 1 (n=15) was receiving daily peritoneal injection through the catheter connected to the abdominal cavity, using PD solution containing 3.86 % D-glucose. Group 2 (n=15) was receiving daily peritoneal injection of 0.9 % physiological saline through a catheter. Group 3 (n=15), which was subjected to sham operation, served as controls. Our results showed that WBC counts in peritoneal effluent of Group 1 were slightly higher than those of Group 2 and control group, respectively (p<0.05). However, there was no episode of infection in any group. In addition, there was no significant difference in neutrophils fractions among these three groups. Hematoxylin-eosin and Masson’s trichrome staining demonstrated a dramatic increase in thickness of the mesothelium-to-muscle layer of peritoneum exposed to high glucose (Group 1) compared to Group 2 and controls (p<0.01). These data indicated that we established a novel rat model of PD with a modified catheter insertion method. This model is more practical, easy to operate, not too expensive and it will facilitate the investigate of long-term effects of PD.

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