Histological Changes Research Articles

Refractive status and histological changes after posterior scleral reinforcement in guinea pig.

To investigate the refractive and the histological changes in guinea pig eyes after posterior scleral reinforcement with scleral allografts. Four-week-old guinea pigs were implanted with scleral allografts, and the changes of refraction, corneal curvature and axis length were monitored for 51d. The effects of methylprednisolone (MPS) on refraction parameters were also evaluated. And the microstructure and ultra-microstructure of eyes were observed on the 9d and 51d after operation. Repeated-measures analysis of variance and one-way analysis of variance were used. The refraction outcome of the implanted eye decreased after operation, and the refraction change of the 3 mm scleral allografts group was significantly different with control group (P=0.005) and the sham surgical group (P=0.004). After the application of MPS solution, the reduction of refraction outcome was statistically suppressed (P=0.008). The inflammatory encapsulation appeared 9d after surgery. On 51d after operation, the loose implanted materials were absorbed, while the adherent implanted materials with MPS group were still tightly attached to the recipient's eyeball. After implantation of scleral allografts, the refraction of guinea pig eyes fluctuated from a decrease to an increase. The outcome of the scleral allografts is affected by implantation methods and the inflammatory response. Stability of the material can be improved by MPS.

Mitochondrial Dysfunction of the Subsynovial Connective Tissue in Patients With Carpal Tunnel Syndrome.

In idiopathic carpal tunnel syndrome (CTS), fibrosis and thickening of the subsynovial connective tissue (SSCT) increase pressure within the carpal tunnel, resulting in median nerve entrapment. Mitochondrial dysfunction in tissues reportedly leads to senescent cell accumulation and various diseases through reduced adenosine triphosphate (ATP) and excessive reactive oxygen species (ROS) production; however, no reports have linked this to CTS. Therefore, this study aimed to evaluate mitochondrial function in SSCTs of patients with CTS. This study investigated SSCTs obtained during carpal tunnel release surgery in patients with CTS (CTS group) and those obtained during tendon transfer or tendon rupture surgery in patients without CTS (control group) from April 2021 to March 2023 at our hospital. Outcome measures included superoxide dismutase (SOD) activity, gene expression levels, immunofluorescence staining, ATP production assays, and transmission electron microscopy (TEM). p values were calculated using the Mann-Whitney U test. The CTS and control groups included 10 and 5 patients (mean age, 67.8 ± 9.57 and 65.4 ± 9.75 years), respectively. The CTS group exhibited decreased SOD activity (p = 0.026), increased gene expression of mitochondrial biosynthetic factors, and decreased mitochondrial ATP production (p = 0.027). The CTS group showed increased mitochondrial ROS production (p = 0.038) on immunofluorescence and larger mitochondrial area (p = 0.030) and fewer mitochondrial cristae (p = 0.045) on TEM. Multiple mitochondrial function assays suggested mitochondrial dysfunction of SSCTs in the CTS group. STATEMENT OF CLINICAL SIGNIFICANCE: This research provided important information on the histological changes in the subsynovial connective tissue within the carpal tunnel in carpal tunnel syndrome.

Minibeam radiotherapy valley dose determines tolerance to acute and late effects in the mouse oral cavity.

Minibeam radiotherapy valley dose determines tolerance to acute and late effects in the mouse oral cavity.

Serum Uromodulin as early marker for ischemic acute kidney injury and nephron loss: association with kidney tissue distribution pattern

BackgroundUromodulin (UMOD) is expressed in kidneys and is mainly excreted in the urine, although a smaller amount is also released into the serum. Here, we investigated UMOD in acute kidney injury (AKI), with particular focus on the utility of serum UMOD as marker for nephron loss.MethodsBlood and kidney samples were collected 6 h, 24 h, 3 days and 8 weeks after ischemia/reperfusion (I/R) in a rat model. To investigate the impact of nephron number on UMOD levels, sera and tissue from healthy, uninephrectomized (Unx) and 5/6-nephrectomized (Snx) rats were analyzed. Histological changes, kidney function and cell damage were evaluated and serum UMOD, Umod mRNA expression and distribution of UMOD protein in the kidney were examined.ResultsIn AKI, kidney function was markedly impaired 24 h after I/R, while kidney injury and serum UMOD was increased transiently. Simultaneously, the amount of UMOD-positive kidney cells rapidly decreased 24 h after I/R compared to healthy kidneys, and mRNA expression of Umod was lowest on days 1–3 after I/R. Serum UMOD correlated with nephron number showing the highest levels in healthy rats, which were reduced after Unx and further reduced after Snx.ConclusionIn an AKI model with severe tubular damage, a transient increase in UMOD serum levels in parallel with loss of UMOD-positive cells suggests temporary release of UMOD from destroyed tubular cells into the blood. Serum UMOD appears to be not only a marker of chronic renal failure but also of acute loss of functional and cellular integrity of kidney epithelia in AKI.

A network toxicology and machine learning approach to investigate the mechanism of kidney injury from melamine and cyanuric acid co-exposure.

A network toxicology and machine learning approach to investigate the mechanism of kidney injury from melamine and cyanuric acid co-exposure.

Time-Dependent Changes in Performance, Biochemistry, and Histology in Dairy Calves with Acute Aflatoxicosis

Time-Dependent Changes in Performance, Biochemistry, and Histology in Dairy Calves with Acute Aflatoxicosis

Thiolutin, a novel NLRP3 inflammasome inhibitor, mitigates IgA nephropathy in mice.

Thiolutin, a novel NLRP3 inflammasome inhibitor, mitigates IgA nephropathy in mice.

Histological Assessment of the Anti-Inflammatory Effectiveness of Peperomia pellucida Extract Administered to the Gingival Sulcus in Rats Induced with Periodontitis.

This study aims to assess the impact of Peperomia pellucida extract on periodontitis in rats, using the Papillary Bleeding Index (PBI), gingival index (GI), and histological evaluation of key inflammatory cells such as osteoclasts, osteoblasts, polymorphonuclear neutrophils (PMNs), macrophages, and fibroblasts to explore its potential in reducing inflammation and preserving periodontal tissue.The extract was prepared using the reflux method with 96% ethanol as a solvent, followed by phytochemical screening and antibacterial testing via the disk diffusion method. This in vivo study utilized a posttest control group experiment with 24 Wistar rats, divided into four groups: nonperiodontitis, no-treatment, chlorhexidine-treated (CHX), and extract-treated groups, with the latter three groups induced with periodontitis. Induction was performed using a 0.3-mm ligature wire and plaque from periodontitis patients, along with nicotine administration (0.001 mg/L) for 7 days. The extract group received a topical application of 2.5 µL of P. pellucida leaf extract, while the CHX group was administered 0.05 mL of CHX daily for 1 week. Observations of GI and PBI were made on days 0, 3, 5, and 7. Histological changes were assessed on day 7 by evaluating the cell counts of osteoclasts, osteoblasts, fibroblasts, macrophages, and PMNs.Data were analyzed using one-way analysis of variance and Kruskal-Wallis with Mann-Whitney post hoc tests for pairwise comparisons.Phytochemical analysis confirmed the presence of alkaloids, polyphenols, tannins, flavonoids, quinones, monoterpenoids, and sesquiterpenoids in P. pellucida extract. The extract demonstrated antibacterial activity against Porphyromonas gingivalis, a key pathogen in periodontitis. Clinical and histological assessments showed significant improvements in the extract-treated group, with outcomes comparable to the CHX-treated group after 7 days.Based on these findings, P. pellucida (L.) Kunth extract contains phytochemicals and exhibits antibacterial and anti-inflammatory properties, as demonstrated by clinical and histological parameters in rats induced with periodontitis.

Celiac Disease—Narrative Review on Progress in Celiac Disease

: Celiac disease is defined as a systemic immunological disorder caused by gluten (gliadin and other prolamin) in genetically predisposed individuals, who present with a variety of gluten-dependent symptoms, specific antibodies, the presence of the HLA DQ2 and DQ8 histocompatibility antigen, and enteropathy. Its prevalence, depending on the studied population and methodology, is estimated at 0.75–1.6% of the general population. During the complex immune reaction it induces, most cells involved in inflammatory processes are activated, which leads to the gradual atrophy of intestinal villi and the proliferation of enterocytes within intestinal crypts. The pathogenesis of celiac disease is extremely complicated and is still the subject of research. According to the current diagnostic guidelines, the following criteria should be taken into account: clinical symptoms (intestinal and extraintestinal), the presence of antibodies against tissue transglutaminase in the IgA class, the level of total IgA, and the presence of typical histological changes in duodenal biopsies. Diet-resistant celiac disease is one of the most important clinical challenges, causing serious complications. Currently, the basic method for treating celiac disease is an elimination diet (i.e., the exclusion of products that may contain gluten from the diet), however, new therapeutic strategies are still being sought, mainly based on supplementation with exogenous endopeptidases, modification of the immune response, and the use of zonulin inhibitors and transglutaminase 2 inhibitors. Clinical trials of new drugs are ongoing. The gradually expanding knowledge about the pathogenesis of celiac disease may allow for the development of new therapeutic strategies for both patients with a mild disease course, as well as those that are diet-resistant.

DLK1 distinguishes subsets of NF1-associated malignant peripheral nerve sheath tumors with divergent molecular signatures

Abstract Purpose: MPNST is the leading cause of premature death among individuals with NF1 and the transcriptional aberrations that precede malignant transformation and contribute to MPNST tumorigenesis remain poorly defined. Alterations involving CDKN2A and components of PRC2 have been implicated as early drivers of PNST evolution, but these events do not occur in all MPNST. Accordingly, emerging data has begun to highlight the importance of molecular-based stratification to improve outcomes in patients with NF1-PNST. Experimental design: Here we perform an integrated analysis of multiple, independent datasets obtained from human NF1 patients to gain critical insight into PNST evolution and MPNST heterogeneity. Results: We show that DLK1 is significantly increased in MPNST and provide evidence that DLK1 overexpression may precede histological changes consistent with malignancy. In complementary analyses, we find that serum levels of DLK1 are significantly higher in both mice and humans harboring MPNST compared to those without malignancy. Importantly, while DLK1 expression is increased in MPNST overall, through the integration of multiple, independent datasets we demonstrate that divergent levels of DLK1 expression distinguish MPNST subsets characterized by unique molecular programs and potential therapeutic vulnerabilities. Specifically, we show that overexpression of DLK1 is associated with the reactivation of embryonic signatures, an immunosuppressive microenvironment and a worse overall survival in patients with NF1-MPNST. Conclusions: Collectively, our findings provide critical insight into MPNST tumorigenesis and support prospective studies evaluating the utility of DLK1 tissue and serum levels in augmenting diagnosis, risk assessment and therapeutic stratification in the setting of NF1-PNST.

The effect of a water-soluble β-glucan on intestinal immunity and microbiota in LPS-challenged piglets

The intestine is the largest immune and barrier organ in the body, and diarrhea and even death during piglet development are related to dysfunction caused by intestinal barrier damage and inflammation. A water-soluble β-glucan produced by Agrobacterium ZX09 has been shown to have a beneficial effect on gastrointestinal health. The main objective of this study was to investigate whether pre-feeding β-glucan has a protective effect on LPS-induced immune stress in piglets. In this study, 24 weaned piglets (21-day-old; 6.64 ± 0.16 kg) were assigned to 4 treatments in a two × two factorial design with diet (with or without β-glucan) and immunological challenge (saline or LPS). Piglets were challenged with saline or LPS after 39 days of feeding 0 or 200 mg/kg β-glucan. The results demonstrated that β-glucan supplementation increased the average daily weight gain and daily feed intake, and decreased diarrhea rate of piglets. Intestinal inflammation symptoms and histological changes in LPS-challenged piglets were alleviated by pre-feeding of β-glucan. β-glucan supplementation reduced serum IL-1β (interleukin-1β) and NO (nitric oxide) secretion in piglets after LPS challenge (0.01 < p < 0.05). Supplementation with β-glucan downregulated the mRNA expression of IL-6 in piglets after LPS challenge (0.01 < p < 0.05). β-glucan supplementation enriched the short-chain fatty acid-producing bacteria, such as Agathobacter and Subdoligranulum (0.01 < p < 0.05), and increased the concentrations of propionate and butyrate (0.01 < p < 0.05). In conclusion, pre-feeding β-glucan can enhance piglet immunity and promote piglet growth by influencing gut microbiota composition and metabolism, and alleviate intestinal damage after LPS challenge.

A Simplified and Robust Model for the Study of Diabetic Nephropathy: Streptozotocin-Induced Diabetic Mice Fed a High-Protein Diet

To better understand diabetic nephropathy (DN), developing accurate animal models is crucial. Current models often fail to fully mimic human DN, showing only mild albuminuria, glomerular hypertrophy, and limited mesangial matrix expansion. Our study aims to develop a more robust model by combining streptozotocin (STZ)-induced diabetes with a high-protein diet (HPD). We divided C57Bl/6J mice into three groups: control, STZ with a standard diet (STZ-SD), and STZ with a HPD (45 kcal% protein) (STZ-HPD) for 12 weeks. Renal function was evaluated using the urinary albumin-to-creatinine ratio, and kidney tissues were analyzed for histological and molecular changes. The STZ-HPD group showed significantly higher albuminuria and more severe glomerular and tubular damage compared to the control and STZ-SD groups. These changes were accompanied by increased inflammatory and oxidative stress markers, highlighting the harmful effects of high-protein intake on renal injury. Our findings suggest that the STZ-HPD model could be a valuable tool for studying DN pathophysiology and evaluating therapeutic interventions, providing a new approach for preclinical research.

Study of the General Toxic Properties of the Vaccine CoviVac in Immature Rats

Relevance. During 2021 and early 2022, the prevalence of COVID-19 in the child population was 9.5%, the frequency of hospitalizations of children and adolescents increased, and fatal outcomes began to be recorded. And in 2022–2023, the proportion of children infected with COVID-19 increased to 18%. At the same time, vaccination remains the most effective way to protect against infection. Studying the safety of vaccines for the prevention of coronavirus infection is an urgent task.Objective of the study. To study the safety of a vaccine for the prevention of a new coronavirus infection in immature animals.Materials and methods. The study was conducted on Wistar rats (60 males and 52 females). During the study, the vaccine or placebo was administered four times with an interval of 2 weeks, in doses of 0.125; 0.25 or 0.5 ml / animal. The dynamics of body weight, animal behavior in the open field test, mass coefficients of internal organs, spermogram were assessed, and histological assessment of the reproductive system organs and the injection site was performed.Results and discussion. No toxic effect of the KoviVak vaccine on animal behavior was revealed, positive dynamics of body weight of experimental animals were recorded. When assessing toxicity in relation to the reproductive system, no effect of placebo or vaccine on spermogram parameters and histological structure of organs was revealed. No effect of placebo and KoviVak vaccine on mass coefficients of internal organs was revealed. Histological changes at the injection site recorded in animals receiving placebo and KoviVak vaccine are explained by the mechanism of action of aluminum hydroxide, which is part of the placebo and vaccine.Conclusion. The preclinical study on juvenile animals showed the safety of the KoviVak vaccine.

Secondary surgical epilepsy as a predictive recurrence factor in patients with grade I meningioma: An observational clinical study

Secondary surgical epilepsy as a predictive recurrence factor in patients with grade I meningioma: An observational clinical study

A Comparative Study on the Adverse Effects of a High-Fat Diet on Testicular Tissue: Exploring the Difference Between Obesity-Prone and Obesity-Resistant Mice.

The impact of a High-Fat Diet (HFD) on male reproductive health is characterized by fertility disorders in obese males, attributed to oxidative stress, endocrine suppression, and upregulation of pro-apoptotic elements. It remains unclear if observed disorders are primarily linked to obesity or if HFD, independently of obesity, induces similar effects in resistant cases. To explore this subject, immature male mice were divided into control (received a normal diet) and experimental groups. After receiving 16 weeks on the HFD regimen (45%, 4.8 kcal/g), the mice were further categorized into control, obesity-prone (HFD-O, weighting 1.4 times higher than control mice), and obesity-resistant (HFD-OR) groups. The histological characteristics, testicular and serum total antioxidant capacity (TAC), testicular malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), lactate, lactate dehydrogenase (LDL), the expression levels of Bcl-2, BAX, and p53 were analyzed. Current study revealed comparable phenotypes in both HFD-received groups, including histological changes, the relative ratio of TAC to MDA, the GSH to GSSG ratio, serum testosterone levels, lactate and LDH content, as well as several parameters related to sperm quality. Despite these similarities, the obesity-prone (HFD-O) group exhibited increased mRNA and protein levels of BAX and p53, while no significant changes were observed in the obesity-resistant (HFD-OR) mice. In conclusion, in obesity-prone condition, HFD disrupted spermatogenesis through metabolic failure and redox imbalance, which in turn increased pro-apoptotic proteins expression. However, regardless of apoptosis, in obesity-resistant condition, HFD disrupted metabolic processes and endocrine capacity in testicular tissue, hindering spermatogenesis through interference with GSH/GSSG and TAC/MDA relative balances.

Effects of Smokeless Tobacco Use on the Upper Gastrointestinal Tract Mucosa: Gross and Histopathological Changes.

Tobacco addiction is prevalent in South and Southeast Asia. This study aimed to assess upper gastrointestinal (GI) tract changes in smokeless tobacco (SLT) users through upper GI endoscopy (UGIE). A cross-sectional observational study, including 108 SLT users and 90 controls who did not use tobacco, was conducted at an Indian tertiary care hospital from March 2022 to February 2023. Participants were categorized into three groups: Non-SLT users (Group A), SLT users for <10 years (Group B), and SLT users for >10 years (Group C). UGIE and biopsies from the lower esophagus, stomach, and duodenum were performed, noting gross and pathological findings. There were 89 males and 19 females. More than 60% of patients used SLT for more than 10 years. Grossly, erosive and ulcerative lesions of the esophagus and stomach were the most common findings. Barrett's esophagus (14/108 patients) and esophageal neoplasms (5/108 patients) were found in 19/108 patients (17.59%). Common biopsy findings were chronic gastritis and duodenitis. Group C had a significantly high finding of gastric ulcers compared to other 2 groups. A total of 68/108 SLT users (62.96%) had Helicobacter pylori infection which was significantly higher compared to the controls (P < 0.05). Chronic SLT use was found to be associated with gross and histological changes in the upper GI tract such as chronic erosions, peptic ulcers, and neoplastic growths. UGIE must be done routinely in all these patients whenever they develop chronic dyspepsia for early diagnosis and management.

Equal performance of HTK-based and UW-based perfusion solutions in sub-normothermic liver machine perfusion

Machine perfusion (MP) is gaining importance in liver transplantation, the only cure for many end-stage liver diseases. Varieties of different MP protocols are available. Currently, various MP protocols are available, differing not only in perfusion temperature but also in the specific perfusion solution required. We aimed to investigate the performance of an HTK-based perfusate during sub-normothermic MP (SNMP) of discarded human liver grafts compared to that of a UW-based solution. Twenty discarded livers (rejected for transplantation by all centers) were subjected to ex-vivo SNMP at 21°C with either HTK- or UW-based solution for 12 h. Perfusate and tissue samples collected before the start, after 6 h, and at the end of SNMP were analyzed for liver enzymes, along with mRNA expression of perfusate and tissue markers associated with organ damage. Hepatocellular viability was assessed by measuring bile production, monitoring pH stability, and analyzing histological changes in HE stained tissue sections. After propensity score matching 16 livers were analyzed. Overall, no differences between HTK- and UW-based solution were detected, except for an increased MLKL mRNA expression and impaired pH stability during SNMP with HTK-based perfusate. No other investigated parameters of cell injury, inflammation or hepatocellular viability supported this finding. Bile production was higher in the 6 HTK-perfused livers compared to the three UW-perfused livers that produced bile. Overall, these findings suggest that HTK performs comparably to a UW-based solution during 12 h of liver SNMP.

Safranal Ameliorates Renal Damage, Inflammation, and Podocyte Injury in Membranous Nephropathy via SIRT/NF-κB Signalling.

Safranal is a natural product from saffron (Crocus sativus L.) with anti-inflammatory and nephroprotective potential. This study aimed to explore the role of safranal in a cationic bovine serum albumin (C-BSA)-induced rat model of membranous glomerulonephritis (MGN). After model establishment, Sprague-Dawley rats were administered 100 or 200mg/kg safranal by gavage. A biochemical analyser was used to measure the urine protein levels and serum levels of renal function parameters. Hematoxylin-eosin and immunofluorescence staining of kidney tissues were performed to examine histopathological changes and assess the expression of IgG, C3, and Sirt1. Western blotting was performed to measure the protein levels of podocin, nephrin, Sirt1, and factors involved in the NF-κB/p65 pathway. Inflammatory cytokine levels in renal homogenates were determined by ELISA. Safranal at 100 or 200mg/kg reduced kidney weight (2.07 ± 0.15g and 2.05 ± 0.15g) and the kidney somatic index (0.83 ± 0.08% and 0.81 ± 0.08%) in MGN rats compared with those in the model group without drug administration (2.62 ± 0.17g and 1.05 ± 0.1%). C-BSA increased the urine protein level to 117.68 ± 10.52mg/day (compared with the sham group, 5.03 ± 0.45mg/day), caused dysregulation of renal function indicators, and induced glomerular expansion and inflammatory cell infiltration in the rat kidney samples. All the biochemical and histological changes were improved by safranal administration. Safranal at two doses also increased the fluorescence intensities of IgG (0.1 ± 0.009 and 0.088 ± 0.008) and C3 (0.065 ± 0.006 and 0.048 ± 0.004) compared with those in the MGN group (0.15 ± 0.013 and 0.086 ± 0.008). Additionally, safranal reversed the downregulation of podocin, nephrin, and Wilms tumor protein-1 (WT1) levels and reversed the high inflammatory cytokine levels in MGN rats. Mechanistically, safranal activated Sirt1 signalling to interfere with NF-κB signalling in the kidney tissues of MGN rats. Safranal ameliorates renal damage, inflammation, and podocyte injury in MGN by upregulating SIRT1 and inhibiting NF-κB signalling.

Protective effect of modafinil in bisphenol A-induced lung injury in rats: roles of SIRT1-dependent signaling pathways.

Bisphenol A (BPA) is an industrial chemical used in manufacturing epoxy resins, polycarbonate plastics. We aimed to evaluate the possible protective effect of modafinil (MOD) in BPA-induced lung injury. Twenty-four adult male albino Wistar rats were divided into four groups: Control group, MOD group: rats received modafinil 10 mg/kg/day for 4 weeks, BPA group: rats received Bisphenol A (500 mg/kg/day) for 4 weeks, MOD/BPA group: rats received MOD+ BPA. We measured arterial blood gas (ABG), malondialdehyde (MDA), nitric oxide (NOx), total antioxidant capacity (TAC), interlukin-1b (IL-1b), Sirtuin type 1 (SIRT1), Keap1, Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), caspase-3 and forkhead-box transcription factor1 (FOXO1) levels, tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), apoptotic Bcl-2-associated protein x (Bax) and anti-apoptotic B-cell leukemia/lymphoma 2 protein (Bcl2) and Heme Oxygenase-1 (HO-1) gene expression. Furthermore; histological changes, interlukin-6 (IL-6) immuno-expression were evaluated. BPA group showed significant increase in the partial pressure of carbon dioxide (PaCO2), MDA, NOx, IL-1b, keap1 and FOXO1, caspase-3 levels; TNF-α and NF-Κb, Bax and HO-1 gene expression, IL-6 exhibited a notable rise in immune-expression in the alveolar wall cells, interstitial cells, and infiltrating inflammatory cells. Moreover; it showed toxic histological changes of marked lung injury. Meanwhile, there is a significant decrease in the partial pressure of oxygen (PaO2), TAC, SIRT1, Nrf2 levels, and Bcl2 gene expression. MOD showed a significant improvement in all parameters. MOD possesses potent ameliorative effects against lung injury caused by BPA via reducing oxidative stress, inflammatory process, and apoptosis through regulation of SIRT1/Nrf2 and SIRT1/FOXO1 signaling pathways.

Veverimer, a Non-Absorbed Gastrointestinal Tract HCl Binder, Decreases Renal Ammoniagenesis and Mitigates Nephrotoxic Serum Nephritis.

Increased tubular ammoniagenesis is an adaptive response to progressive kidney disease, facilitating net acid excretion. However, excess ammonia production can also exacerbate kidney disease progression, in part, by activating the alternative complement cascade. Oral Na bicarbonate therapy can decrease the systemic H+ burden, limiting ammonia production. However, poor compliance limits bicarbonate's efficacy. Veverimer is an oral, Na+ free, non-absorbed polymer that binds H+ within the gastrointestinal (GI) tract. This stimulates GI carbonic anhydrase-mediated bicarbonate production and systemic bicarbonate uptake. Hence, the goals of this study were to: test whether GI HCl binding decreases renal tubular ammoniagenesis; assess whether decreased complement activation results; and determine whether these changes can mitigate nephrotoxic serum (NTS) nephritis in which complement activation may play a role. A normal diet ± veverimer (4.5% w/w) was fed to normal mice for ∼1 week. Veverimer's impact on plasma bicarbonate, blood/urinary pH, urinary ammonia excretion, and tubular H+ transporter, NHE3, density were assessed. Additional mice were fed the normal or veverimer diet following NTS injection. Urine protein, albumin, ammonia, C5b-9 excretion, and plasma C3a levels were measured at 1 and/or 2 weeks post NTS injection. Renal histologic changes (H/E stain; C5b-9, CD45 immunohistochemistry), and selected injury mediators/biomarkers (NGAL, IL-6, MCP-1, TGF beta 1, endothelin-1 mRNAs) were also assessed. Veverimer increased plasma bicarbonate/urinary pH, reduced urinary ammonia, and decreased NHE3 in normal mice. Veverimer also reduced NTS-induced proteinuria/albuminura, urinary ammonia, and C5b-9 excretion (by ∼60%, ∼75%, ∼50%, respectively). Significant reductions in NTS-induced glomerular/ tubulointerstitial injury, inflammatory/profibrotic gene expression, renal C5b-9 deposition, and suppressed plasma C3a levels were observed. Oral bicarbonate also conferred protection, implicating bicarbonate in veverimer's beneficial effect. Veverimer-mediated bicarbonate generation can suppress renal ammoniagenesis and complement activation. These findings suggest a potential benefit of veverimer/ bicarbonate therapy in selected complement-mediated renal diseases.