BUN Levels Research Articles

Ameliorating Effect of Triticum aestivum (WG) Against Cisplatin-Induced Nephrotoxicity: Role of Cytokines, Free Radicals and Apoptotic Cascade

Objectives Cisplatin (CP) is a most potent chemotherapeutic agent; however, CP causes nephrotoxicity that limits its therapeutic utility. Triticum aestivum called wheatgrass (WG) is a strong antioxidant and potent detoxifying herb that has not only been studied for anticancer activity but also for efficacy and safety when combined with anticancer drugs. This study investigated the efficacy of WG against CP-induced nephrotoxicity. Methods Male rats were allocated into five sets of six rats in each: (1) normal control (NC), (2) CP-treated (7.5 mg/kg) as positive control (PC), (3) WG-200 mg/kg alone, and (4) CP with WG-100, and (5) CP with WG-200 mg/kg groups. Hydro-alcoholic extract of WG was administered orally to the animals for two weeks, and CP was administered intraperitoneally to the respective groups on the 10th day to induce nephrotoxicity. Serum was used for kidney function and kidneys for histological examination and quantification of apoptosis markers, pro-inflammatory cytokines and oxidative stress. Results CP-induced nephrotoxicity was apparent from histological damage and increased levels of BUN, Cr and UA. CP also caused an increase in malondialdehyde and decreased superoxide dismutase (SOD), glutathione (GSH), catalase (CAT) activities and led to up-regulation of pro-inflammatory cytokines and apoptosis markers. WG caused a significant decrease in Cr, BUN, UA, MDA and increase in GSH, SOD and CAT activities. Conclusion WG ameliorated histological damage and led to a reversal of cytokines and apoptosis markers. Both doses of WG effectively ameliorated CP-induced nephrotoxicity; thus, during chemotherapy, WG could be a promising adjunct to CP.

Protective Effects of Black Rice Anthocyanins on D-Galactose-Induced Renal Injury in Mice: The Role of Nrf2 and NF-κB Signaling and Gut Microbiota Modulation

Background/Objectives: This study aimed to evaluate the renal protective effects of black rice anthocyanins (BRAs) against renal injury in mice induced by D-galactose (D-gal). Methods: The renal aging mouse model was established by thirteen consecutive weeks of subcutaneous injections of D-gal. The serum levels of urea nitrogen (BUN), creatinine (CRE), uric acid (UA), antioxidant enzymes (e.g., GSH-Px and SOD), and total antioxidant capacity (T-AOC), as well as the contents of inflammatory factors (IL-1β, IL-6, and TNF-α) in kidney tissues were evaluated. Additionally, the relative expression of the NQO1, HO-1, IKKβ, NF-kBp65, and TLR4 proteins was examined. Results: BRA treatment significantly reduced serum levels of BUN, and CRE increased the concentrations of antioxidant enzymes and total antioxidant capacity in renal tissues, and reduced the levels of inflammatory factors. Furthermore, BRAs restored the relative expression of the NQO1, HO-1, IKKβ, NF-kBp65, and TLR4 proteins to normal levels and promoted the recovery of the renal tissue architecture. Conclusions: It was demonstrated that BRAs could potentially prevent and protect against kidney injury by modulating the Nrf2 and NF-κB signaling pathways, attenuating oxidative stress and inflammatory responses, and modulating the gut microflora. These findings provide a scientific basis for the application of BRAs as a natural bioactive substance in the field of nephroprotection, especially against the renal degeneration that accompanies the aging process.

The Abnormal Expression of Tubular SGLT2 and GULT2 in Diabetes Model Mice with Malocclusion-Induced Hyperglycemia

Background: A relationship between malocclusion and the promotion of diabetes has been suggested. In hyperglycemia, the expression of sodium–glucose cotransporter 2 (SGLT2) and the facilitative glucose transporter 2 (GLUT2) is upregulated in proximal tubular cells, leading to an increase in renal glucose reabsorption. The present study aimed to investigate whether malocclusion contributes to diabetic exacerbation. Methods: Streptozotocin (STZ)-induced diabetic mice with malocclusion due to cutting molars were investigated based on increased blood glucose levels. PCR and immunohistochemical analyses were performed on diabetic mice kidneys to investigate the expression of SGLT2 and GLUT2. Results: Animal experiments were performed using 32 mice for 21 days. The time to reach a diabetic condition in STZ-administered mice was shorter with malocclusion than without malocclusion. The increase and mean blood glucose levels in STZ-administered mice were steeper and higher with malocclusion than without malocclusion. Urea albumin, BUN, and CRE levels were higher in diabetic mice with malocclusion than in diabetic mice without. Immunoreaction with anti-SGLT2 and anti-GLUT2 in the renal tissue of STZ-administered mice was stronger with malocclusion than without malocclusion. The amounts of SGLT2 and GLUT2 mRNA in the renal tissue in STZ-administered mice were higher with malocclusion than without malocclusion. The amounts of TNF-a and IL-6 mRNA in the large intestinal tissue in STZ-administered mice were higher with malocclusion than without malocclusion. Conclusions: Our results indicate that malocclusion accelerates the tubular expression of SGLT2 and GLUT2 under hyperglycemia. Malocclusion may be a diabetes-exacerbating factor with increased poor glycemic control due to shortened occlusion time resulting from swallowing food without chewing.

Subchronic Exposure to Low-Dose Chlorfenapyr and Emamectin Benzoate Disrupts Kidney Metabolism in Rats.

Residues of the pesticides chlorfenapyr (CFP) and emamectin benzoate (EMB) often coexist in the environment and can be accumulated in the body. To understand the impact of these two chemicals on health, we investigated their effect on the kidneys. In this study, rats were treated with CFP and/or EMB at low/medium/high doses of 1/3/9 mg/kg/day and 0.2/0.6/1.8 mg/kg/day, respectively, via oral gavage for 60 days. Kidneys and serum samples were collected and serum biochemistry and kidney histopathological changes were analyzed and examined. Kidney metabolome alterations were analyzed by using gas chromatography-mass spectrometry. The results showed that combined exposure to CFP and EMB elevated BUN levels and induced pathological damage, which presented as thinner renal tubular epithelial cells, an abnormal glomerular morphology, and an increased fibrotic area. CFP and/or EMB disrupted glutathione metabolism and carbohydrate metabolism, resulting in the alteration of kidney metabolomes and inducing oxidative stress in the cells of kidney tissues. In addition, CFP decreased ATP content and inhibited pyruvate PDH activity in the kidneys. These findings suggest that long-term exposure to CFP and EMB at environmentally relevant levels induce alterations in the renal metabolome, oxidative stress, and an insufficient energy supply, which may contribute to renal histopathological damage.

5β-hydroxycostic acid from Laggera alata ameliorates sepsis-associated acute kidney injury through its anti-inflammatory and anti-ferroptosis effects via NF-κB and MAPK pathways.

The whole plant of Laggera alata is frequently utilize to remedy inflammatory diseases including nephritis as a traditional Chinese medicine. However, its active ingredients and mechanism of action against sepsis-associated acute kidney injury (SA-AKI) are unknown. This study aimed to identify active compounds from L. alata that inhibit renal inflammation and ameliorate SA-AKI, and to elucidate their mechanisms of action. The chemical constituents were separated from the ethyl acetate layer of L. alata methanol extract by column chromatography over silica gel, medium-pressure liquid chromatography and semipreparative high-performance liquid chromatography. Extensive spectroscopic techniques were applied to determine the chemical structures. The anti-inflammatory efficiency was measured by analyzing the NO production in RAW 264.7 cells. The levels of IL-6, IL-1β, CCL-2 and CCL-5 mRNA were determined by qRT-PCR. Cecal ligation and puncture (CLP) surgery is a frequently applied method to establish the mouse sepsis model. Sepsis was thus induced in mice via CLP. The effect in the treatment of SA-AKI was evaluated by H&E staining and ELISA detection. Western blotting was used to evaluate the protein levels involved in ferroptosis, NF-κB and MAPK signaling pathways. Twelve compounds were obtained from L.alata including four unreported sesquiterpenoids (1-4). Compound 5 exhibited the most significant inhibitory effect on NO production with the IC50 value of 6.034 μM and could restrain the mRNA expression of inflammatory factors IL-6, IL-1β, CCL-2 and CCL-5. The in vivo results demonstrated that compound 5 alleviated the renal injury by decreasing the serum IL-6, IL-1β, Cr, and BUN levels, reducing the kidney contents of Cys-C and KIM-1, and regulating the kidney levels of MDA, GSH, ferrous iron, GPX4, FTH1, and SLC7A11. Furthermore, Compound 5 also repressed the NF-κB and MAPK pathways in vitro and in vivo. This study revealed that compound 5 could ameliorate SA-AKI through exerting its anti-inflammatory and anti-ferroptosis effects via NF-κB and MAPK pathways. The current research supported the traditional use of L.alata in the treatment of renal diseases.

Efficacy of melatonin on drug- or contrast-induced acute kidney injury: a systematic review and GRADE-assessed meta-analysis of experimental and clinical studies.

The objective of this systematic review and meta-analysis was to assess the efficacy of melatonin in drug- or contrast-induced AKI in preclinical and clinical studies. PubMed, Embase, Scopus, Web of Science (WOS), the Cochrane Database of Systematic Reviews (CDSR), and clinical trials.GOV from the beginning until August 1, 2024. On the basis of the inclusion and exclusion criteria, the articles were included by two independent researchers. Data regarding study design, patient characteristics, the number of patients with and without AKI, and the means and SDs of the serum creatinine and BUN levels were extracted from relevant studies. STATA version 17.0 was used to compute pooled measures of standardized mean differences, standardized mean differences, risk ratios and risk differences. I2 and chi-square tests were used to assess heterogeneity between studies. Funnel plots, Egger tests and the trim-and-fill method were used to evaluate small study effects (publication bias). The risk of bias of the included clinical and preclinical studies was assessed via the Cochrane ROB tool and SYRCLE tool, respectively. The credibility of the results was evaluated via GRADE. Sensitivity analysis was performed via the one-out removal method. We identified 1,696 nonduplicate records, of which the full texts of 159 articles were examined. Twenty-nine animal experimental studies and 5 clinical trials met the inclusion criteria and were included in the review. The results of the meta-analysis confirmed that melatonin was significantly effective at reducing the serum creatinine level (standardized mean difference: -3.04; 95% CI -3.904 to -2.183, with 95% prediction interval: -7.201 to 1.163) and the BUN level (standardized mean difference: -3.464; 95% CI -4.378 to -2.549, with 95% prediction interval: -7.839 to 0.911) in drug-induced AKI animal studies. Melatonin did not have a significant effect on the serum creatinine level (standardized mean difference: -2.67; 95% CI -9.69 to -4.35, with 95% prediction interval: -42.618 to 37.278) or the BUN level (standardized mean difference: -1.77; 95% CI -5.533 to -1.994, with 95% prediction interval: -22.943 to 19.404) in contrast-induced AKI animal studies. Furthermore, in clinical studies, melatonin had no significant effect on reducing the serum creatinine level (standardized mean difference: 0.183; 95% CI -1.309 to 1.675, with 95% prediction interval: -7.975 to 8.340), BUN level (standardized mean difference: 0.206; 95% CI -0.0871 to 1.283, with 95% prediction interval: -5.115 to 5.528) or risk of AKI incidence (risk ratio: 0.877; 95% CI 0.46 to 1.64, with 95% prediction interval: -0.238 to 3.174; risk difference: -0.06mg/dl; 95% CI -0.259 to 0.40mg/dl, with 95% prediction interval: -0.467 to 0.348). There were no significant publication biases, and after sensitivity analysis, no considerable changes were observed, indicating the robustness of the results. This meta-analysis indicates that melatonin may protect against drug-induced AKI in animal models but is not effective in clinical studies and that melatonin has no significant effect on contrast-induced AKI. Owing to the inconclusive results in clinical trials and very low certainty of evidence, further research with higher methodological quality is needed to reach a more certain conclusion.

The dual impact: physiological and psychological effects of rapid weight loss in wrestling.

Athletes competing in weight-class sports often seek to gain an advantage by competing at lower weights. Athletes competing in weight-class sports often seek to gain an advantage by competing at lower weights. To achieve this, they aim to lose weight during the competition period, leading to various physiological and psychological changes. This study aimed to investigate the biochemical, hormonal, and psychological effects of weight reduction in elite wrestlers during the competition phase. Thirty-seven elite male free style wrestlers (age: 19.02 ± 1.27) participated in the study. Samples were collected 5 days before and on the day of the match. A significant decrease in body weight was observed (p < 0.05). Levels of creatine, BUN, sodium, hematocrit, hemoglobin, LDH, and cortisol increased, while albumin, testosterone, and FSH levels decreased. There were no significant differences in potassium, ALT, AST, TSH levels. State and trait anxiety scores of the wrestlers increased significantly during the RWL period. The study concluded that elite wrestlers experienced significant changes in physiological and psychological parameters during the competition periods. These findings underscore the importance of careful monitoring of RWL strategies by coaches and athletes to mitigate the adverse effects on nutritional status, psychological well-being, and physical performance.

The Material Basis for the Beneficial Effects of Paidu Powder on Hyperuricemia: A Network Pharmacology and Clinical Study

Background: Paidu powder (PDP) is a formula that is used in traditional Chinese medicine (TCM) practices and has been demonstrated to be effective to lower blood uric acid (UA) level.Methods: Network pharmacology was employed to probe the mechanistic basis for the beneficial effects of PDP. Then, PDP was subjected to Aspergillus oryza AS3.042 fermentation, and the primary bioactive compounds in the resultant samples were analyzed via HPLC. A clinical study was then performed to test the therapeutic effects of unfermented and fermented PDP on HUA.Results: Network pharmacology strategies identified 122 active compounds and 924 HUA‐related target genes, with 61 overlapping targets relative to PDP and HUA ultimately being selected. These target genes were associated with 474 GO biological process terms and 136 KEGG pathways. Moreover, good binding was observed between three main bioactive compounds of interest and nine primary target proteins. Notably, the levels of the top three bioactive compounds (quercetin, kaempferol, and naringenin) were significantly elevated by 308.96%, 1386.44%, and 719.21%, respectively, following fermentation. Clinical analyses indicated that both PDP and fermented PDP treatment significantly reduced UA, CRE, and BUN levels (p &lt; 0.01), with a higher overall efficacy rate in the fermented PDP group relative to the unfermented PDP group (p &lt; 0.01). Fewer adverse reactions were also observed in the fermented PDP group.Conclusion: These results offer novel insights into the putative mechanisms through which PDP can exert its beneficial effects against HUA, offering a novel basis for the identification of the pharmacological effects of this popular TCM prescription.

Granisetron ameliorates doxorubicin-evoked nephrotoxicity via modulation of Nrf2 and TLR4/p38 MAPK/NLRP3 signals in rats.

Doxorubicin (DOX) is an anthracycline chemotherapy employed in treating malignancies. Unfortunately, the clinical application of DOX is limited due to its nephrotoxicity. Granisetron (GRAN) is a 5-HT3 receptor blocker used widely to manage post-chemotherapy nausea and vomiting with anti-inflammatory, anti-oxidant, and anti-apoptotic bioactivities. We plan to examine the renoprotective effect of GRAN against DOX-associated renal toxicity. In this investigation, twenty-four adult male Wistar rats were allocated to control, DOX (30 mg/kg, i.p), and GRAN (2.5 mg/kg, p.o) + DOX groups. GRAN attenuated renal impairment induced by DOX in rats by decreasing the BUN, creatinine, KIM-1, and Cys-C levels, and such finding is supported by attenuating histological alterations caused by DOX. GRAN combated oxidative stress proved by decreasing MDA content and elevating GSH and CAT levels mediated by Nrf2 activation. GRAN suppressed inflammation evidenced by decreasing IL-6 and TNF-α levels mediated by downregulation of inflammatory sensitive controllers TLR-4, NLRP3, and p38 MAPK. GRAN prevented apoptosis by controlling renal expression of BAX, caspase-3 and Bcl2. Therefore, GRAN holds promise agent against DOX-induced renal toxicity by upregulating Nrf2 and suppressing apoptosis and inflammatory cascadeTLR4/p38 MAPK/ NLRP3.

Iristectorin A Ameliorates Cisplatin-Induced Hepatorenal Injury in Mice Through Modulation of the Nrf2/HO-1 Signaling Pathway.

Cisplatin (CIS) is a chemotherapeutic agent frequently used in cancer treatment. However, depending on the dosage and duration of use, CIS can lead to hepatotoxicity and nephrotoxicity. Iristectorin A (IRIS), a natural flavonoid, has been found to exhibit antioxidant and protective effects. In this paper, we scrutinized the effects and molecular mechanisms of the IRIS on CIS-induced liver and kidney damage in mice. IRIS administration alleviated CIS-induced elevations in AST, ALT, ALP, BUN, and creatinine levels by approximately 12%, 15%, 11%, 21%, and 15%, respectively. It also inhibited liver and kidney MDA levels by approximately 29% and 28%, while enhancing liver and kidney GSH, SOD, and CAT levels by 47%-60%, 85%-70%, and 90%-55%, respectively. IRIS enhanced liver and kidney mRNA expression levels of Nrf2 (by approximately 1.6- and 1.5-fold, respectively), HO-1 (by 1.5- and 1.5-fold, respectively), and Bcl-2 (by 1.5- and 1.4-fold, respectively). In addition, IRIS suppressed the mRNA expression levels of NF-κB (by 0.7- and 0.7-fold), TNF-α (by 0.7- and 0.7-fold), Bax (by 0.8- and 0.7-fold), and Cas-3 (by 0.9- and 0.7-fold). Protein expression analysis revealed that IRIS increased Nrf2 (by 1.5- to 1.2-fold) and Bcl-2 levels (by 1.3- to 1.7-fold), and reduced Bax (by 0.7- to 0.8-fold) and Cas-3 (by 0.8- and 0.8-fold) levels altered by CIS treatment. Moreover, IRIS administration prevented histopathological changes in the liver and kidney caused by CIS. Ultimately, IRIS was found to substantially mitigate CIS-induced hepatorenal injury by targeting oxidative stress, inflammation, and apoptosis through regulation of the Nrf2/HO-1 signaling pathway. Therefore, IRIS holds potential as a therapeutic adjuvant in the use of CIS.

Neferine Targeted the NLRC5/NLRP3 Pathway to Inhibit M1-type Polarization and Pyroptosis of Macrophages to Improve Hyperuricemic Nephropathy.

Neferine (Nef) has a renal protective effect. This research intended to explore the impact of Nef on hyperuricemic nephropathy (HN). Adenine and potassium oxonate were administered to SD rats to induce the HN model. Bone marrow macrophages (BMDM) and NRK-52E were used to construct a transwell co-culture system. The polarization of BMDM and apoptosis levels were detected using immunofluorescence and flow cytometry. Renal pathological changes were detected using hematoxylin-eosin (HE) and Masson staining. Biochemical methods were adopted to detect serum in rats. CCK-8 and EDU staining were used to assess cell activity and proliferation. RT-qPCR and western blot were adopted to detect NLRC5, NLRP3, pyroptosis, proliferation, and apoptosis-related factor levels. After Nef treatment, renal injury and fibrosis in HN rats were inhibited, and UA concentration, urinary protein, BUN, and CRE levels were decreased. After Nef intervention, M1 markers, pyroptosis-related factors, and NLRC5 levels in BMDM stimulated with uric acid (UA) treatment were decreased. Meanwhile, the proliferation level of NRK-52E cells co-cultured with UA-treated BMDM was increased, but the apoptosis level was decreased. After NLRC5 overexpression, Nef-induced regulation was reversed, accompanied by increased NLRP3 levels. After NLRP3 was knocked down, the levels of M1-type markers and pyroptosis-related factors were reduced in BMDM. Nef improved HN by inhibiting macrophages polarized to M1-type and pyroptosis by targeting the NLRC5/NLRP3 pathway. This research provides a scientific theoretical basis for the treatment of HN.

Protective effect of ascorbic acid against renal injury induced by 3-chloropropane-1,2-diol-dipalmitate in rats

3-monochloropropane-1,2-diol esters (3-MCPDE) are a group of contaminants which are mainly formed during heat processing of edible oil and fat-based foods. The kidney is the primary target organ for the toxic effects of 3-MCPDE. 3-MCPD-di-palmitate exists in a variety of oils and fats, and is the most common and relatively high proportion of 3-MCPDE. In this study, we investigated the protective effect of ascorbic acid on 3-MCPD-di-palmitate-induced renal injury in rats. Thirty 8-week-old male Sprague-Dawley rats were randomly divided into 5 groups, namely control, 3-MCPD-di-palmitate (240 mg/kg·bw), 3-MCPD-di-palmitate (240 mg/kg·bw) + ascorbic acid (100 mg/kg·bw), 3-MCPD-di-palmitate (240 mg/kg·bw) + ascorbic acid (200 mg/kg·bw) and 3-MCPD-di-palmitate (240 mg/kg·bw) + ascorbic acid (500 mg/kg·bw). These treatments were administered via gavage for a duration of 4 weeks. The effects of ascorbic acid on 3-MCPDE-induced kidney injury in rats were investigated by evaluating the kidney index, renal function (BUN, CRE), renal histopathology, oxidative stress markers (ROS, GSH, MDA, and T-AOC), DNA oxidation marker (8-OHdG), and activities of Caspase 3 and 9. The results showed that the exposure to 3-MCPDE significantly increased the kidney index, BUN and CRE levels, ROS and MDA levels, 8-OHdG levels, and activities of Caspase 3 and 9, while decreasing GSH and T-AOC. The combined treatment with 3-MCPDE and ascorbic acid can effectively restore the aforementioned parameters. The present study concluded that ascorbic acid effectively attenuates the renal apoptosis and oxidative homeostasis induced by 3-MCPDE uptake thereby intervening in renal injury.

Thymoquinone in a Rat Model of Mesenteric Ischemia-Reperfusion Injury

Aim: The objective of this study was to assess the protective efficacy of thymoquinone at low and high doses against ischemic reperfusion (I/R) injury resulting from superior mesenteric artery occlusion in rats. Materials and Methods: Thirty-five Wistar Albino rats were randomly divided into five groups: control, sham, two thymoquinone treatment groups (50 and 100 mg/kg), and a DMSO control. Intestinal injury was assessed using the Park/Chiu classification system. Blood samples were analyzed for liver enzymes (ALT, AST, ALP), kidney function markers (BUN), and other markers (LDH, phosphorus). Results: DMSO and low dose thymoquinone groups showed significantly better Park and Chiu scores (p values were 0.015 and p=0.016 respectively) High-dose thymoquinone and DMSO groups had significantly higher ALT levels than the control. Sham, low-dose thymoquinone, and DMSO groups had significantly higher AST levels than the control. Both low-dose and high-dose thymoquinone groups had significantly higher BUN levels than the control. Conclusion: Our study suggested that low-dose thymoquinone was more effective than high-dose thymoquinone in mitigating I/R-induced intestinal injury. High-dose thymoquinone appeared to have a detrimental effect on intestinal tissue, as evidenced by the lack of significant improvement in histopathological scores compared to the sham group. Conclusion: Our findings suggest that thymoquinone at low doses is more effective in I/R injury than at high doses. Pure DMSO and low dose thymoquinone groups showed a similar protective effect; however pure DMSO caused more deterioration in laboratory findings than low dose thymoquinone.

Correlation between Serum Biomarkers and Disease Progression of Chronic Kidney Disease.

Aims/Background The present study aimed to assess the capability of biomarkers, including inflammatory indicators, anaemic markers, lipid markers, and renal function indices, to differentiate between different stages of chronic kidney disease (CKD). Expected to provide a new strategy for monitoring the development of CKD and stratified treatment management, providing valuable insights for future biomarker studies to explore early detection of CKD. Methods The changes in inflammatory markers (interferon gamma [IFN-γ], interleukin [IL]-17A, IL-10, IL-6, IL-4, IL-2, IL-1 and white blood cells [WBC]), lipid markers (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], and triglyceride [TG]), indicators of kidney injury (serum creatinine [Scr] and blood urea nitrogen [BUN]) in 451 patients with different stages of CKD were examined. Furthermore, these markers were compared between 299 anemic patients and 53 non-anemic patients. Univariate and multivariate regression analyses were employed to analyze the association between these biomarkers and estimated glomerular filtration rate (eGFR). To identify risk factors associated with the development of CKD, we utilized principal component analysis to evaluate their utility as potential diagnostic and prognostic markers for the disease. Results Significant differences were found in IL-6, BUN, and hemoglobin (Hb) levels across CKD stages 2 to 5. Anaemic individuals had elevated levels of IL-6, Scr, and BUN compared to non-anaemic individuals. In addition, the multivariate linear regression analysis revealed that IL-1 (p = 0.022), IL-6 (p = 0.022), Hb (p < 0.001), and BUN (p < 0.001) were statistically significant predictors of eGFR. Furthermore, it was discovered that the blood levels of IL-6 (p = 0.012), BUN (p < 0.001), and Hb (p < 0.001) were risk factors associated with the stages of CKD. Conclusion Serum levels of IL-6, BUN and Hb have been associated with the progression of CKD. Using a combination of serum biomarkers is a potential strategy for tracking the development of CKD, facilitating stratified management and early intervention.

Assessment of Nephroprotective Properties of Vitex Agnus castus Extract in Cisplatin-Treated Wistar Rats: A Pilot Study

Background: Cisplatin (CP) is used to treat various solid tumors but is associated with nephrotoxicity, which varies with dose and duration. Vitex Agnus castus (VAC) berries, known for their anti-inflammatory and antioxidant properties, may alleviate CP-induced renal toxicity. Objective: To investigate the gender-specific responses to cisplatin-induced nephrotoxicity and evaluate VAC extract's nephroprotective effects. Methods: Four-month-old Wistar rats (n=36) (24 male, 12 female) were used. In phase 1, gender-based differences in CP-induced nephrotoxicity were assessed. The gender group with higher nephrotoxicity was selected for phase 2 to evaluate VAC's nephroprotective properties. Animals were randomly grouped as Normal Control (6 males &amp; 6 females), CP Control (6 males &amp; 6 females) received CP (7 mg/kg bw) injection, VAC Control (received 165 mg/kg bw VAC for 7 days daily), and CP+VAC (CP injection followed by VAC orally for 7 days). Results: CP-treated male rats showed significantly higher plasma creatinine, urea, and BUN levels (p&lt;0.05) than controls, while female rats showed slight increases. Male rats were chosen for phase 2, where VAC treatment post-CP injection lowered the kidney function parameters, though not significantly compared to CP controls. Histopathology revealed severe tubular damage and dilation in CP-treated kidneys compared to controls. Conclusion: Cisplatin (7 mg/kg bw) causes acute kidney injury, with male rats showing more nephrotoxicity. VAC extract reduced biochemical markers of nephrotoxicity but did not reverse CP-induced damage, suggesting potential mitigation of some CP-induced renal toxicity.

Effect of SARS-CoV-2 infection on liver function in patients with hepatitis B

ObjectiveTo investigate the impact of SARS-CoV-2 infection on liver function and prognosis in patients with HBV infection.MethodsA total of 154 HBV-positive patients (HBV ( +) group) and 154 HBV-negative patients (HBV (-) group) diagnosed with COVID-19 at Taizhou Hospital between December 10, 2022, and January 31, 2023, were included in this study. Clinical characteristics, treatment, and laboratory findings were collected from patients at three time points: before (T1), during (T2), and at the time of discharge (T3) from SARS-CoV-2 infection.ResultsCompared to the HBV (-) group, the HBV ( +) group had a longer hospital stay (15 (9–22) days vs. 9 (5–16) days). Longitudinal comparisons of laboratory indicators from T1 to T3 showed a continuous decline in TP and ALB levels and a continuous increase in PT and TT levels in the HBV ( +) group. BUN levels increased during T2 and decreased thereafter. These differences were considered statistically significant (P < 0.05). Notably, the HBV ( +) group had a higher proportion of indicators elevated > 3 ULN from T1 to T2, including ALT (1.95%/5.19%), AST (3.25%/12.99%), ALP (1.95%/3.25%), GGT (4.55%/9.09%), TBIL (6.49%/9.09%), and DBIL (18.18%/22.73%). In the HBV (-) group, the elevations were mainly concentrated within 1–2 ULN, including AST (12.99%/22.08%), DBIL (10.39%/21.43%), BUN (12.99%/22.08%), CREA (20.13%/29.22%), and PLT (7.79%/14.94%). Furthermore, the incidence of liver injury from T1 to T3 was higher in the HBV ( +) group compared to the HBV (-) group (15.7% (20/127) vs. 7.2% (11/152), P < 0.05). Multivariate analysis showed that liver cirrhosis (HR = 4.847, 95% CI: 1.224–19.20, P = 0.025) and liver cancer (HR = 8.333, 95% CI: 2.156–32.209, P = 0.002) were independent risk factors for liver injury in the presence of SARS-CoV-2 infection.ConclusionSARS-CoV-2 infection has a higher proportion of liver injury in HBV-infected patients, affecting hepatic protein synthesis function. Those with cirrhosis and hepatocellular carcinoma are at higher risk of severe liver injury.

Protective effect of deinoxanthin in sorafenib-induced nephrotoxicity in rats with the hepatocellular carcinoma model.

Sorafenib is a synthetic compound and an orally administered multichines inhibitor that targets growth signaling and angiogenesis. It is widely recognized as the standard of care for advanced hepatocellular carcinoma (HCC) but has toxic side effects. Deinoxanthin, purified from the radioresistant bacterium Deinococcus radiodurans, has strong antioxidant characteristics. In this study, the protective effect of deinoxanthin against sorafenib-induced nephrotoxicity was investigated in a rat model of hepatocellular carcinoma. In this regard, the expressions of DDAH1, KIM1, and INOS genes were examined, histopathological and immunohistochemical analyses were performed, and various parameters such as SOD, MDA, GST, CAT, TAS, and TOS were tested biochemically. BUN and creatinine levels were measured in renal tissues. RT-qPCR, Western blot, and ELISA methods were used for all these analyses. As a result, the analyses show that deinoxanthin, which has a high antioxidant capacity, reduces kidney injury and can be used as a protective agent. The primary objective of this study is to evaluate the potential of deinoxanthin as a protective agent against the nephrotoxic side effects of sorafenib in HCC. Our study identified the potential synergistic effects of sorafenib and deinoxanthin on nephrotoxicity in rats with hepatocellular carcinoma.

Discovery of cyanidin-3-O-galactoside as a novel CNT2 inhibitor for the treatment of hyperuricemia.

Inhibition of human concentrative nucleoside transporter 2 (CNT2) could suppress increases in serum urate levels derived from dietary purines. However, the structural basis for substrate recognition of CNT2 is still unknown and only a few inhibitors have been reported. In this study, a homology model of CNT2 was constructed and residues T315, E316, N426, N491, E492, F536 and N538 were identified as binding sites for adenosine through site-directed mutagenesis and a 3H-adenosine uptake assay. To explore potential CNT2 inhibitors, a database containing 4704 saccharides and glycosides was constructed, followed by high-throughput virtual screening. The top 20 compounds with the highest docking scores were then evaluated their in vitro activity. Among them, cyanidin-3-O-galactoside (Cy3Gal) demonstrated the most potent inhibitory activity against CNT2, exhibiting an IC50 value of 9.40μM. Docking analysis revealed that residues M314, T315, T347, N422, F536 and S541 contributed to a strong binding affinity with Cy3Gal. In addition, Cy3Gal exhibited minimal inhibitory effects on CNT3 and equilibrative nucleoside transporters (ENTs) in vitro. At doses of 5-20mg/kg, Cy3Gal effectively reduced serum and urine levels of uric acid and adenosine in vivo. The CCK-8 assay revealed that Cy3Gal displayed minimal cytotoxicity to mTEC and hIEC cells at a concentration of 100μM. The serum CR and BUN levels indicate that Cy3Gal does not exhibit any apparent renal toxicity compared to lesinurad and allopurinol. HE examination showed no noticeable pathological changes in the kidneys or colons after treatment with Cy3Gal. In summary, Cy3Gal could be a CNT2 inhibitor with favorable drugability for the treatment of hyperuricemia.

Identification of circulating microbial DNA and its association with kidney function in patients with diabetic kidney disease.

Recently, substantial studies have been accumulated to indicate the important role of gut microbiota in diabetic kidney disease (DKD). The abnormal change of bacterial-derived products could imply specific injuries or play beneficial or harmful roles in DKD progression. In this study, we examined the presence and contribution of the Klebsiella oxytoca gene in the circulation of patients with DKD. We enrolled a total of 16 healthy participants, 17 patients with DKD, 5 patients with DKD requiring haemodialysis (HD), and 7 patients with CKD without diabetes. Bacterial-derived DNA (16S rDNA and a specific K. oxytoca gene) in the blood was detected using droplet digital PCR, then investigated the relationship with clinical characteristics. We identified an increase in K. oxytoca genes in the blood of DKD patients. Interestingly, blood K. oxytoca copies and K. oxytoca/ 16S DNA ratio correlated with higher blood creatinine and BUN levels together with lower eGFR in DKD patients. K. oxytoca levels were also associated with higher neutrophil percentage, lower lymphocyte frequency, and increased neutrophil-to-lymphocyte ratio. Collectively, the presence of the K. oxytoca gene in the circulation could serve as a biomarker reflecting reduced renal function in DKD patients.

Exploring the molecular mechanisms for renoprotective effects of Huangkui capsule on diabetic nephropathy mice by comprehensive serum metabolomics analysis.

Huangkui capsule (HKC), a patent traditional Chinese medicine, has shown significant efficacy in managing chronic kidney disease (CKD), particularly diabetic nephropathy (DN). Previous studies have shown that HKC can alleviate kidney damage in DN. However, the exact mechanisms through which it exerts its effects remain unclear. This study aimed to elucidate the potential molecular mechanisms of HKC in treating kidney injury in type 1 diabetic nephropathy (T1DN) models through serum metabolomics, Chinmedomics, and molecular docking techniques. T1DN mouse models were induced by intraperitoneal injection of streptozotocin (STZ), resulting in the ACR value ten times that of the control group. The efficacy of HKC on T1DN was comprehensively evaluated in general conditions, renal coefficient, histopathology, and related biochemical indicators. UPLC-Q-TOF-MS/MS based serum metabolomics was employed to identify biomarkers of T1DN and evaluate the effects of HKC. Relevant pathways were analyzed, and followed by Protein-Protein Interaction network analysis to screen for key enzymes. By integrating the Chinmedomics strategy and molecular docking the relationship between these targets and active components was elucitaed. HKC resulted in a significant reduction in renal inflammation and fibrosis, as evidenced by the decreased levels of urinary ACR, blood TG, T-CHO, BUN, and renal TNF-α and VEGF-A, along with a reduction in the positive area of COL-1. Palmitic acid, stearic acid, arachidonic acid, pantothenic acid, and sphingosine-1-phosphate serve as key serum metabolite biomarkers for T1DN, involved in the biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, pantothenate and CoA biosynthesis, and sphingolipid metabolism. FASN, Cyp2e1, and Cyp4a32 are the key enzymes in the treatment of T1DN with HKC. Additionally, 8 key active components were identified in the serum of HKC-H, including quercetin, myricetin, isoquercitrin, hyperoside, hibifolin, gentisic acid 5-O-β-glucoside, floramanoside F, and quercetin-4'-O-glucoside, which are believed to interact with key enzymes. The active components of HKC influence Fasn, Cyp2e1, and Cy4a32, improving renal injury in T1DN. These findings provide new molecular insights for the future clinical application and research of HKC in treating T1DN.