Pig Kidney Research Articles

Determination of selenium speciation in the muscle, kidney, and liver from different animals treated with different selenium supplements by HPLC‐ICP‐MS

AbstractDietary selenium (Se) deficiency is recognized as a global problem, and exogenous Se supplementation can effectively enrich its levels in animal bodies. Offal tissues are equally important as meat in Se enrichment. Varying properties among Se species require information beyond total Se concentration to fully evaluate health risk/benefits. In the present study, the reliable inductively coupled plasma mass spectrometry (ICP‐MS) and HPLC‐ICP‐MS methods were optimized to analyze total Se content and Se speciation in the muscle and kidney of sheep, kidney and liver of pig, and liver of chicken after different Se supplementation treatments. The total Se contents in the liver and kidney were higher than in muscle. Five Se species were detected in the muscle, and selenourea was additionally detected in the liver and kidney. Sheep muscle and chicken liver mainly contained selenomethionine, and other tissues mainly contained selenocysteine. As the levels of selenomethionine or selenium‐enriched yeast increased in the feed, the proportion of selenomethionine in the sample increased, as well as the proportion of selenocysteine decreased, and almost no inorganic selenium was detected in all tissues. This study has provided insights for analyzing the Se enrichment patterns in tissues, which is significant for understanding the Se metabolism, animal health, and enriching the dietary Se supplementation for humans.

Opinions on the Future of Clinical Pig Kidney Xenotransplantation.

Based on promising results obtained in primate models, pioneers in the US have now started to explore the new frontier of genetically-edited pig-to-human transplantation. The recent transition of xenotransplantation into clinical medicine has included transplants in brain-dead subjects and the compassionate use of xenotransplants in living recipients without options for allotransplantation. While the barrier of hyperacute rejection seems to be successfully overcome by gene editing of donor pigs, the occurrence of accelerated rejection could pose significant limitations to the success of the procedure. Ultimately, the establishment of efficient and safe strategies to overcome immunologic barriers will, among other critical factors, such as potential xenozoonotic disease transmission or physiological differences, determine whether and for which indications xenotransplantation will be viable. Considering preliminary outcomes of compassionate use xenotransplantions, which may raise questions about how faithfully data from non-human primate models translate into human outcomes, further research in decedents may be necessary before proceeding with additional clinical transplants. Looking ahead, designing systematic trials in xenotransplantation, including the definition of acceptable eligibility criteria for such high-risk transplants, will be an immense challenge, especially in kidney transplantation, where dialysis provides an effective alternative to transplantation in most cases.

Normothermic Machine Perfusion Reconstitutes Porcine Kidney Tissue Metabolism But Induces an Inflammatory Response, Which Is Reduced by Complement C5 Inhibition.

Normothermic machine perfusion (NMP) is a clinical strategy to reduce renal ischemia-reperfusion injury (IRI). Optimal NMP should restore metabolism and minimize IRI induced inflammatory responses. Microdialysis was used to evaluate renal metabolism. This study aimed to assess the effect of complement inhibition on NMP induced inflammatory responses. Twenty-two pig kidneys underwent 18h of static cold storage (SCS) followed by 4h of NMP using a closed-circuit system. Kidneys were randomized to receive a C5-inhibitor or placebo during SCS and NMP. Perfusion resulted in rapidly stabilized renal flow, low renal resistance, and urine production. During SCS, tissue microdialysate levels of glucose and pyruvate decreased significantly, whereas glycerol increased (p < 0.001). In the first hour of NMP, glucose and pyruvate increased while glycerol decreased (p < 0.001). After 4h, all metabolites had returned to baseline. Inflammatory markers C3a, soluble C5b-9, TNF, IL-6, IL-1β, IL-8, and IL-10 increased significantly during NMP in perfusate and kidney tissue. C5-inhibition significantly decreased perfusate and urine soluble C5b-9 (p < 0.001; p = 0.002, respectively), and tissue IL-1β (p = 0.049), but did not alter other inflammatory markers. Microdialysis can accurately monitor the effect of NMP on renal metabolism. Closed-circuit NMP induces inflammation, which appeared partly complement-mediated. Targeting additional immune inhibitors should be the next step.

Diffractive hyperchromatic objective for chromatic confocal microscopy.

The limited focal shift of conventional achromatic objectives constrains the maximum imaging depth of chromatic confocal microscopes. To address this, we designed a hyperchromatic confocal microscope using diffractive optical elements, which was fabricated by single-point diamond turning (SPDT). This design takes advantage of the small Abbe number of diffractive optical elements to introduce a significant longitudinal chromatic shift. The resulting chromatic confocal microscope achieved a maximum imaging depth of 750 µm and a lateral resolution of 0.78 µm across a wavelength range of 600-810 nm. The system's imaging capabilities were demonstrated by capturing detailed images of biological samples, including cucumber seed cavities, pig kidney, and human forearm skin. These results confirmed the microscope's effectiveness in visualizing key cellular structures, underscoring its potential for high-resolution biological imaging.

Relationship between renal pelvis pressure and post-ureteroscopy infection in a live swine model.

To evaluate the relationship between renal pelvis pressure and infection after ureteroscopy, using a live swine model. In anaesthetised pigs, a 1-h ureteroscopy was performed using a pressure-sensing guidewire, with renal pelvis pressure maintained at either 37 mmHg or 75 mmHg for the entire procedure and infusion with saline alone or with a standardised concentration of uropathogenic Escherichia coli strain CFT073 (1.5 × 107 colony-forming units [CFU]/mL). Venous blood sampling was performed during and after the procedure. Vital signs, inflammatory biomarkers, and renal tissue and blood cultures were assessed. In 21 pig kidneys, study groups were: 37 mmHg with saline irrigation (n = 3); 75 mmHg with saline irrigation (n = 4); 37 mmHg with saline irrigation with 1.5 × 107 CFU/mL E. coli (n = 7); and 75 mmHg with saline irrigation with 1.5 × 107 CFU/mL E. coli (n = 7). Statistically significant changes in inflammatory biomarkers were most pronounced in the group with 75 mmHg saline irrigation + E. coli and were significantly elevated compared with the control group and the group receiving E. coli irrigation at 37 mmHg. Positive blood cultures were noted in 5/7 animals treated with E. coli at 75 mmHg; no others developed bacteraemia. In this swine model of ureteroscopy, irrigation with saline + E. coli at a renal pelvis pressure of 75 mmHg resulted in bacteraemia and inflammatory biomarker elevations significantly greater than both E. coli irrigation with renal pelvis pressure maintained at 37 mmHg and the control.

Characterizing coagulation responses in humans and nonhuman primates following kidney xenotransplantation-A narrative review.

The recent report of the first pig kidney transplant in a living human brings hope to thousands of people with end-stage kidney failure. The scientific community views this early success with caution as kidney xenotransplantation exhibits many challenges and barriers. One of these is coagulation dysregulation. This includes (i) pig von Willebrand Factor (vWF) interaction with human platelets, which can induce abnormal clotting responses, heightening the risk of graft failure, (ii) the inefficiency of pig thrombomodulin in activating human protein C, which emphasizes the species-specific variations that aggravate coagulation challenges, and (iii) the development of thrombotic microangiopathy in the pig grafts and the occurrence of systemic consumptive coagulopathy in the recipients. Indeed, coagulation dysregulation largely results from differences in endothelial cell response and incompatibilities between pig and human coagulation-anticoagulation pathways. These barriers can be resolved by modifications to pig vWF and the expression of human thrombomodulin and endothelial protein C receptors in pig cells, serving as strategic interventions to align the coagulation systems of the two species more closely. These coagulation challenges have clinical implications in how they affect graft survival and patient outcome. Genetic engineering of the organ-source pig and the administration of various drugs have assisted in correcting this coagulation dysregulation. Hence, comprehending and controlling coagulation dysregulation is crucial for progress in xenotransplantation as a viable option for treating patients with terminal kidney disease.

The isolation and serotyping of foot-and-mouth disease virus in Iran during 2019-2022.

Foot-and-mouth disease (FMD) is a significant transboundary animal disease that has a considerable economic impact on livestock systems worldwide. In order to determine the presence and type of FMD virus in Iran, a total of 90 samples of vesicular fluid and epithelial tissue were collected from the tongues, tooth pads, and hooves of clinically suspect cattle on 40 vaccinatedfarms in 9 provinces of Iran. These samples were collected duringfour years, from January 2019 to December 2022, and the vaccine was a locally produced polyvalent inactivated vaccine. The collected samples were analyzed using ELISA and isolation methods to identify and characterize the FMD virus. The results of the ELISA tests revealed that 66.66% of the samples were positive for FMD, and the serotypes of the virus were determined. Considering ELISA reslut, 62% of the samples were assigned to serotype O, 33% to serotype A, and 5% to serotype Asia-1. Furthermore, 90% of the positive samples were inoculated onto monolayer cultures of pig kidneys (IB-RS2) for isolation and antigen detection by serotype-specific ELISA kit. The great majority of detected serotype Oviruses were from Esfahan province, while the most detectedserotype Aand serotype Asia-1 viruses were from Qom and Tehran provinces, respectively. These findings indicate that the ELISA and isolation methods are suitable for identifying and typing FMD viruses. The vaccination program in Iran, which includes three serotypes (O, A, and Asia-1), appears to be effective in controlling the spread of the disease. However, the continued circulation of these serotypes in most provinces suggests that ongoing surveillance and vaccination efforts are necessary.

Evaluating different methods for kidney recellularization

This study explores a potential solution to the shortage of kidneys for transplantation in end-stage renal disease (ESRD). Currently, kidney transplantation stands as the optimal option, yet the scarcity of organs persists. Employing tissue engineering, researchers sought to assess the feasibility of generating kidneys for transplantation. Pig kidneys were utilized since they possess higher similarities to human kidneys. Cells were removed via decellularization, which maintains the organ’s microarchitecture. Subsequently, pig kidney cells and human red blood cells were perfused into the vacant kidney structure to reconstitute it. The methodologies employed showed promising results, suggesting a viable approach to increase the recellularization rate in whole pig kidneys. This proof-of-concept establishes a groundwork for potentially extending this technology to human kidneys, tackling the organ shortage, thus positively enhancing outcomes for ESRD patients by increasing the availability of transplantable organs.

Ablation efficiency and laser safety of a novel superpulsed thulium fiber laser: a in vitro study.

To assess the ablation efficiency of the Superpulsed Thulium Fiber Laser (SP-TFL) and investigate the thermal effects of SP-TFL. A SP-TFLwas employed to evaluate ablation efficiency. Fresh ex-vivo pig kidneys and ureters were utilized to evaluate the renal pelvis and ureter temperature changes, different irrigation rates(0, 15, 38mL/min) and a long pulse width were used. The research indicated that as laser output power increased, ablation rates significantly increased. Ablation rates(mg/min) were higher and the energy per ablated mass(J/mg) was lower at lower frequencies(10-50Hz). Under the same frequency and single pulse energy, super short and short pulse widths demonstrated higher ablation rates at higher frequencies (exceeding 100Hz). The temperature of the renal pelvis and ureter decreased with increasing irrigation rates. In the renal pelvis, without irrigation, the temperature quickly reached the critical threshold of 43℃. The irrigation rate was 15ml/min and power was no more than 18W, the renal pelvis temperature did not reach 43℃. When the irrigation rate were 38ml/min, the temperature did not risen to 43℃. In the ureter, without irrigation, the temperature also quickly reached 43℃. The temperature reached 43℃ when the power exceeded to12W with an irrigation rate of 15ml/min. With an irrigation rate of 38ml/min, the temperature reached 43℃ at a laser power of 30W. The SP-TFL demonstrated promising ablation effectiveness especially for lower frequencies and super short and short pulse widths model. Proper irrigation rates, single pulse energy, frequency and pulse width are crucial during lithotripsy.

The Time Has Come: The Case for Initiating Pilot Clinical Trials of Pig Kidney Xenotransplantation.

In vitro studies indicate that kidney transplantation from gene-edited pigs in which expression of all three of the known glycan xenoantigens has been deleted may be more challenging in nonhuman primates (NHPs) than it will be in human recipients. Furthermore, pig-to-human xenotransplantation offers several other advantages - (i) the patient can communicate with the surgical team; (ii) recipient microbiological monitoring and environment will be clinical-grade; and (iii) sophisticated graft monitoring and imaging techniques, (v) therapeutic interventions, e.g., dialysis, plasmapheresis, and (v) intensive care can be deployed that are not easily available in NHP laboratory models. We suggest, therefore, that progress to develop safe, informative human clinical trials will be accelerated if pilot clinical cases are initiated. The selection of patients for kidney xenotransplantation can include those who are at high risk of dying imminently, e.g., those experiencing increasing vascular access challenges with no realistic alternative therapy available, and those who have been accepted onto the waitlist for an allograft, but who are unlikely ever to receive one. Patients with an increased risk of dying include those with (i) age >60 years, (ii) blood groups O or B, and (iii) diabetic nephropathy. UNOS data indicate that an average of 25 patients on the kidney waitlist in the USA die or are removed from the list every day (i.e., >9,000 each year). Given the improved xenograft survival observed in preclinical studies, we suggest that it is time to plan a small pilot clinical trial for healthy dialysis patients who understand the risks and potential benefits of kidney xenotransplantation.

Diets enriched with chicory-derived native inulin can affect kidney and liver mineral content in nursery pigs

Diets enriched with chicory-derived native inulin can affect kidney and liver mineral content in nursery pigs

Enabling SENSE accelerated 2D CSI for hyperpolarized carbon-13 imaging

As hyperpolarized (HP) carbon-13 (13C) metabolic imaging is clinically translated, there is a need for easy-to-implement, fast, and robust imaging techniques. However, achieving high temporal resolution without decreasing spatial and/or spectral resolution, whilst maintaining the usability of the imaging sequence is challenging. Therefore, this study looked to accelerate HP 13C MRI by combining a well-established and robust sequence called two-dimensional Chemical Shift Imaging (2D CSI) with prospective under sampling and SENSitivity Encoding (SENSE) reconstruction. Due to the low natural abundance of 13C, the sensitivity maps cannot be pre-acquired for the reconstruction. As such, the implementation of sodium (23Na) sensitivity maps for SENSE reconstructed 13C CSI was demonstrated in a phantom and in vivo in the pig kidney. Results showed that SENSE reconstruction using 23Na sensitivity maps corrected aliased images with a four-fold acceleration. With high temporal resolution, the kidney spectra produced a detailed metabolic arrival and decay curve, useful for further metabolite kinetic modelling or denoising. Metabolic ratio maps were produced in three pigs demonstrating the technique’s ability for repeat metabolic measurements. In cases with unknown metabolite spectra or limited HP MRI specialist knowledge, this robust acceleration method ensures comprehensive capture of metabolic signals, mitigating the risk of missing spectral data.

Biocompatible Liquid Embolic for the Treatment of Microvascular Hemorrhage.

Persistent or recurrent bleeding from microvessels inaccessible for direct endovascular intervention is a major problem in medicine today. Here, an innovative catheter-directed liquid embolic (P-LE) is bioengineered for rapid microvessel embolization to treat small vessel hemorrhage. Tested in rodent, porcine, and canine animal models under normal and coagulopathic conditions, P-LE outperformed clinically used embolic materials in both survival and non-survival experiments, effectively occluding vessels as small as 40 microns with no signs of recanalization. P-LE occlusion is independent of the coagulation cascade, and its resistance to displacement is ≈ 8 times greater than systolic blood pressure. P-LE is also found to be biocompatible and x-ray visible and does not require polymerization or a chemical reaction to embolize. To simulate the clinical scenario, acute microvascular hemorrhage is created in the pig kidney, liver, or stomach; these are successfully treated with P-LE achieving immediate hemostasis. Furthermore, P-LE is found to be bactericidal to highly resistant patient-derived bacteria, suggesting that P-LE may also protect against infectious complications that may occur following embolization procedures. P-LE is safe, easy to use, and effective in treating -microvessel hemorrhage.

447.7: Multi-omic profiling in a human decedent receiving a pig kidney xenograft reveals concerted immune responses preceding a biopsy confirmed rejection event.

447.7: Multi-omic profiling in a human decedent receiving a pig kidney xenograft reveals concerted immune responses preceding a biopsy confirmed rejection event.

Revealing the lethal effects of Pasteurella multocida toxin on multiple organ systems.

Pasteurella multocida toxin (PMT) is one of the most important virulence factors of Pasteurella multocida type D. Pasteurella multocida infection has caused enormous economic losses in the pig farming industry. Although it is well known that this bacterial infection causes progressive atrophic rhinitis, its effects on other organ tissues in pigs are unclear. In this study, PMT was expressed and purified, and the cytotoxic effects of PMT on four types of swine cells, LLC-PK1, PAM, IPEC, and ST, were investigated. LLC-PK1 exhibited the highest sensitivity to the cytotoxic effects of PMT. Our studies revealed that a PMT concentration of 0.1 μg/kg can lead to weight loss, whereas a PMT concentration of 0.5 μg/kg can lead to death in mice. PMT causes damage to the intestines, kidneys, lungs, livers, and spleens of mice. Furthermore, PMT caused acute death in pigs at treatment concentrations greater than 5 μg/kg; at PMT concentration of 2.5 μg/kg, weight loss occurred until death. PMT mainly caused damage to the hearts, lungs, livers, spleens and kidneys of pigs. The organ coefficient showed that damage to the heart and kidneys was the most severe and caused the renal pelvis and renal pyramid to dissolve and become cavitated. Pathology revealed hemorrhage in the lungs, liver, and spleen, and the kidneys were swollen and vacuolated, which was consistent with the damaged target organs in the mice. In conclusion, these findings demonstrate that PMT is extremely toxic in vitro and in vivo, causing damage to various organs of the body, especially the kidneys and lungs. This study provides a theoretical basis for the in-depth exploration of the cytotoxic effects of PMT on target organs.

Ex Vivo Simultaneous H215O Positron Emission Tomography and Magnetic Resonance Imaging of Porcine Kidneys-A Feasibility Study.

Pig kidneys (n = 7) were connected to a NMP circuit. PET/MRI was performed at two different pump flow levels: a blood-oxygenation-level-dependent (BOLD) MRI sequence performed simultaneously with a H215O PET sequence for determination of RBP. RBP was measured using H215O PET in all kidneys (flow 1: 0.42-0.76 mL/min/g, flow 2: 0.7-1.6 mL/min/g). We found a linear correlation between changes in delivered blood flow from the perfusion pump and changes in the measured RBP using PET imaging (r2 = 0.87). Our study demonstrated the feasibility of combined H215O PET/MRI during NMP of isolated porcine kidneys with tissue oxygenation being stable over time. The introduction of H215O PET/MRI in nephrological research could be highly relevant for future pre-transplant kidney evaluation and as a tool for studying renal physiology in healthy and diseased kidneys.

Complex-valued multi-frequency electrical impedance tomography based on deep neural networks

The utilization of multi-frequency electrical impedance tomography (mfEIT), a non-invasive imaging technique, allows for the visualization of the conductivity distribution in biological tissues across different frequencies. However, the analysis of phase angle information within complex impedance remains a challenge, as most existing deep learning-based mfEIT algorithms are limited to real number processing. To mitigate this limitation, this study proposes a comlex reconstruction method which is inspired by the idea of combining deep learning with traditional reconstruction algorithm. It uses a spare Bayesian learning algorithm in the preprocessing stage that can perform complex arithmetic operations, and fully learns and makes use of the correlation between the real and imaginary parts to reconstruc the distribution of complex-valued conductivity in the measurement area. After that, an altered UNet network is used to further optimize the pre-reconstruction outcomes. The experimental outcomes validate the efficacy of the proposed algorithm in accurately reconstructing the complex-valued conductivity distributions of diverse biological tissues, such as potato and pig kidney, across different frequencies. Furthermore, the algorithm exhibits exceptional performance in mitigating the presence of image artifacts during the reconstruction process.

Investigation of Functional Cytochrome P450 4A Enzymes in Liver and Kidney of Pigs, Cats, Tree Shrews, and Dogs in Comparison with the Metabolic Capacity of Human P450 4A11.

Pigs are sometimes used in preclinical drug metabolism studies, with growing interest, and thus their drug-metabolizing enzymes, including the cytochromes P450 (P450 or CYP; EC 1.14.14.1), need to be examined. In the present study, novel CYP4A cDNAs were isolated and characterized, namely, pig CYP4A23 and CYP4A90; cat CYP4A37 and CYP4A106; and tree shrew CYP4A11a, CYP4A11d, CYP4A11e, CYP4A11f, and CYP4A11g. For comparison, the following known CYP4A cDNAs were also analyzed: pig CYP4A21 and dog CYP4A37, CYP4A38, and CYP4A39. These CYP4A cDNAs all contained open reading frames of 504-513 amino acids and had high amino acid sequence identity (74%-80%) with human CYP4As. Phylogenetic analysis of amino acid sequences revealed that these CYP4As were clustered in each species. All CYP4A genes contained 12 coding exons and formed a gene cluster in the corresponding genomic regions. A range of tissue types were analyzed, and these CYP4A mRNAs were preferentially expressed in liver and/or kidney, except for pig CYP4A90, which showed preferential expression in lung and duodenum. CYP4A enzymes, heterologously expressed in Escherichia coli, preferentially catalyzed lauric acid 12-hydroxylation and arachidonic acid 20-hydroxylation, just as human CYP4A11 does, with the same regioselectivity (i.e., at the ω-position of fatty acids). These results imply that dog, cat, pig, and tree shrew CYP4As have functional characteristics similar to those of human CYP4A11, with minor differences in lauric acid 12-hydroxylation. SIGNIFICANCE STATEMENT: Cytochrome P450 (P450, CYP) 4As are important P450s in human biological processes because of their fatty acid-metabolizing ability. Pig CYP4A21, CYP4A23, and CYP4A90; cat CYP4A37 and CYP4A106; tree shrew CYP4A11a, CYP4A11d, CYP4A11e, CYP4A11f, and CYP4A11g; and dog CYP4A37, CYP4A38, and CYP4A39 cDNAs were isolated and analyzed. These CYP4A cDNAs shared relatively high sequence identities with human CYP4A11 and CYP4A22. Pig, cat, tree shrew, and dog CYP4As in the liver and kidneys are likely to catalyze the ω-hydroxylation of fatty acids.

Pig organs in humans: a forum on xenotransplantation

ABSTRACT What if one of your organs, say, the kidney, the heart or the liver, deteriorates completely, and you are not lucky enough to have a human organ for transplantation? Do you want to receive an organ from a pig? That is not a joke, but a subject some physicians and researchers are working on—a field of research known as ‘xenotransplantation’.In 2022, David Bennett, a 57-year-old patient with terminal heart disease, received a pig heart and survived for 2 months after the surgery. Another recipient, Lawrence Faucette, survived for 40 days after similar surgery in 2023. Then, in 2024, Rick Slayman, the world's first recipient of a pig kidney, passed away 2 months after the surgery. Rick was able to get out of the hospital during these 2 months and the transplant team said there is no indication that his sudden passing was the result of failure of the pig kidney graft. Rather, it was related to his heart disease. In China, a liver xenotransplantation from pig to a brain-dead patient was reported in 2024 and the transplanted liver survived in the human body for as long as 10 days.On April 2024, National Science Review organized a panel discussion on xenotransplantation, which was chaired by Prof. Liangxue Lai and involved six other experts in the field. The panelists had in-depth discussions on xenotransplantation, covering its history and the (i) gene editing of the donor pigs, (ii) immunosuppressive regimens required by the recipients, (iii) challenges in preclinical and clinical research, (iv) relevant ethical issues and (v) prospects for the future of xenotransplantation. Gang Chen Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China David K.C. Cooper Massachusetts General Hospital, Harvard Medical School, Boston, USA Yifan Dai School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China Dengke Pan ClonOrgan Biotechnology Company, Neijiang, China Lin Wang Xijing Hospital, Air Force Medical University, Xi'an, China Xuan Zhang Xijing Hospital, Air Force Medical University, Xi'an, China Liangxue Lai (Chair) Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China

Inositol-6-phosphate mitigates deoxynivalenol nephrotoxicity in pig kidney explants

Abstract Deoxynivalenol (DON) is a mycotoxin that frequently contaminates food crops and negatively impacts human and animal health. While inositol-6-phosphate (IP6) is known to counteract DON-induced intestinal damage, inflammation, and oxidative stress, its ability to alleviate DON-caused kidney injury is yet unexplored. This study assessed DON’s kidney effects and IP6’s protective capability using an ex vivo renal explants model. From 360 explants taken from six pigs, four groups were formed: control (culture medium), DON (10 μM equivalent to 3 mg/kg of feed), IP6 group (5 mM), and DON + IP6 (10 μM + 5 mM). DON elevated creatinine levels and γ-glutamyl transferase activity in the culture medium. It led to cytoplasmic vacuolation in convoluted tubular epithelial cells and tubular necrosis, a drop in antioxidant potential (ABTS) and a rise in interleukin (IL)-8 mRNA. The introduction of IP6 restored renal histological and functional parameters, bolstered antioxidant status, enhanced IL-10 gene expression, and reduced superoxide anion levels. These results indicate that within the model of renal explants, IP6 significantly alleviates the nephrotoxic effects of DON while efficiently regulating the antioxidative and anti-inflammatory response within the kidneys.