Hesperidin alleviates zinc-induced nephrotoxicity via the gut-kidney axis in swine.

Introduction: Zinc (Zn) is an essential trace element in animals, but excessive intake can lead to renal toxicity damage. Thus, the exploration of effective natural antagonists to reduce the toxicity caused by Zn has become a major scientific problem. Methods: Here, we found that hesperidin could effectively alleviate the renal toxicity induced by Zn in pigs by using hematoxylin-eosin staining, transmission electron microscope, immunohistochemistry, fluorescence quantitative PCR, and microfloral DNA sequencing. Results: The results showed that hesperidin could effectively attenuate the pathological injury in kidney, and reduce autophagy and apoptosis induced by Zn, which evidenced by the downregulation of LC3, ATG5, Bak1, Bax, Caspase-3 and upregulation of p62 and Bcl2. Additionally, hesperidin could reverse colon injury and the decrease of ZO-1 protein expression. Interestingly, hesperidin restored the intestinal flora structure disturbed by Zn, and significantly reduced the abundance of Tenericutes (phylum level) and Christensenella (genus level). Discussion: Thus, altered intestinal flora and intestinal barrier function constitute the gut-kidney axis, which is involved in hesperidin alleviating Zn-induced nephrotoxicity. Our study provides theoretical basis and practical significance of hesperidin for the prevention and treatment of Zn-induced nephrotoxicity through gut-kidney axis.

Drug-induced Kidney Disease: Revisited.

Drug-induced kidney disease (DIKD) is a frequent cause of acute and chronic kidney disease (CKD) that leads to high morbidity, hospitalization, and increased healthcare costs. There is a need to constantly update our knowledge in this field, given the ever-burgeoning list of newer treatments that are emerging, especially in the field of cancer immunotherapy. Generalizing the complex pathways causing DIKD from different agents, the common mechanisms include direct toxicity, immune-mediated injury, and drug-induced alterations in renal blood flow. Proper management of this condition involves risk minimization, early detection of renal damage, and timely discontinuation of potential agents to avoid irreversible renal damage.

The Impact of the Aryl Hydrocarbon Receptor on Antenatal Chemical Exposure-Induced Cardiovascular-Kidney-Metabolic Programming.

Early life exposure lays the groundwork for the risk of developing cardiovascular-kidney-metabolic (CKM) syndrome in adulthood. Various environmental chemicals to which pregnant mothers are commonly exposed can disrupt fetal programming, leading to a wide range of CKM phenotypes. The aryl hydrocarbon receptor (AHR) has a key role as a ligand-activated transcription factor in sensing these environmental chemicals. Activating AHR through exposure to environmental chemicals has been documented for its adverse impacts on cardiovascular diseases, hypertension, diabetes, obesity, kidney disease, and non-alcoholic fatty liver disease, as evidenced by both epidemiological and animal studies. In this review, we compile current human evidence and findings from animal models that support the connection between antenatal chemical exposures and CKM programming, focusing particularly on AHR signaling. Additionally, we explore potential AHR modulators aimed at preventing CKM syndrome. As the pioneering review to present evidence advocating for the avoidance of toxic chemical exposure during pregnancy and deepening our understanding of AHR signaling, this has the potential to mitigate the global burden of CKM syndrome in the future.

Mitochondrial SIRT3 as a protective factor against cyclosporine A-induced nephrotoxicity.

Sirtuin3 (SIRT3), a mitochondrial deacetylase, has been shown to be involved in various kidney diseases. In this study, we aimed to clarify the role of SIRT3 in cyclosporine-induced nephrotoxicity and the associated mitochondrial dysfunction. Madin-Darby canine kidney (MDCK) cells were transfected with Flag-tagged SIRT3 for SIRT3 overexpression or SIRT3 siRNA for the inhibition of SIRT3. Subsequently, the cells were treated with cyclosporine A (CsA) or vehicle. Wild-type and SIRT3 knockout (KO) mice were randomly assigned to receive cyclosporine A or olive oil. Furthermore, SIRT3 activator, honokiol, was treated alongside CsA to wild type mice. Our results revealed that CsA treatment inhibited mitochondrial SIRT3 expression in MDCK cells. Inhibition of SIRT3 through siRNA transfection exacerbated apoptosis, impaired the expression of the AMP-activated protein kinase-peroxisome proliferator-activated receptor gamma coactivator 1 alpha (AMPK-PGC1α) pathway, and worsened mitochondrial dysfunction induced by CsA treatment. Conversely, overexpression of SIRT3 through Flag-tagged SIRT3 transfection ameliorated apoptosis, increased the expression of mitochondrial superoxide dismutase 2, and restored the mitochondrial regulator pathway, AMPK-PGC1α. In SIRT3 KO mice, CsA treatment led to aggravated kidney dysfunction, increased kidney tubular injury, and accumulation of oxidative end products indicative of oxidative stress injury. Meanwhile, SIRT3 activation in vivo significantly mitigated these adverse effects, improving kidney function, reducing oxidative stress markers, and enhancing mitochondrial health following CsA treatment. Overall, our findings suggest that SIRT3 plays a protective role in alleviating mitochondrial dysfunction caused by CsA through the activation of the AMPK-PGC1α pathway, thereby preventing further kidney injury.

Kefir mitigates renal damage caused by zearalenone in female wistar rats by reducing oxidative stress.

The estrogen-like mycotoxin zearalenone (ZEA) was popularly occurred in several food and feeds, posing threats to human and animal health. ZEA induced renal toxicity and caused oxidative stress. In the current study, the protecting effect of kefir administration against ZEA-induced renal damage in rats was explored. Rats were divided into 4 groups, each consisting of 5 animals. For the initial 7 days, they were orally administered sterile milk (200 µL/day). Subsequently, during the second week, the groups were exposed to kefir (200 µL/day), ZEA (40 mg/kg b.w./day) and a combination of kefir and ZEA. The biochemical parameters, kidney histological changes and ZEA residue were assessed. Kefir supplementation enhanced the antioxidant enzymes in the kidney, such as superoxide dismutase, catalase and glutathione peroxidase activities, which increased by 1.2, 4 and 20 folds, respectively, relative to the ZEA group. Remarkably, the concomitant administration kefir + ZEA suppressed ZEA residues in both serum and kidney. Additionally, serum levels of blood urea nitrogen, uric acid and renal malondialdehyde decreased by 22, 65 and 54%, respectively, in the kefir + ZEA group; while, the creatinine content increased by around 60%. Rats co-treated with kefir showed a normal kidney histological architecture contrary to tissues alterations mediated in the ZEA group. These results suggest that kefir may showed a protective effect on the kidneys, mitigating ZEA-induced acute toxicity in rats.

Dysregulation of ferroptosis may participate in the mitigating effect of CoCl2 on contrast-induced nephropathy.

BACKGROUND: Contrast agents can directly or indirectly induce renal tubular ischemia and hypoxic damage. Given that cobalt chloride (CoCl2) can protect renal tubules, the protective effect and potential mechanism of action of CoCl2 on contrast-induced nephropathy (CIN) warrant investigation. METHODS: A CIN mouse model was established to determine the protective effect of CoCl2 on renal injury in vivo. Then, TMT-based proteomics was performed to determine the differentially expressed proteins (DEPs), following which, enrichment analyses of gene ontology and the KEGG pathway were performed. In vitro, a CIN model was constructed with renal tubular epithelial cells (HK-2) to determine the effect of CoCl2 on potential targets and the role of the key protein identified from the in vivo experiments. RESULTS: CoCl2 treatment decreased the levels of BUN and serum creatinine (sCr), while increasing the levels of urea and creatinine (Cr) in the urine of mice after CIN injury. Damage to the renal tubules in the CoCl2 treatment group was significantly less than in the CIN model group. We identified 79 DEPs after treating the in vivo model with CoCl2, and frequently observed ferroptosis-related GO and KEGG pathway terms. Of these, Hp (haptoglobin) was selected and found to have a strong renoprotective effect, even though its expression level in kidney tissue decreased after CoCl2 treatment. In HK-2 cells, overexpression of Hp reduced the ferroptosis caused by erastin, while knocking down Hp negated the attenuation effect of CoCl2 on HK-2 cell ferroptosis. CONCLUSION: CoCl2 attenuated kidney damage in the CIN model, and this effect was associated with the decrease in ferroptosis mediated by Hp.

Comparison of preventive effects of combined furosemide and mannitol versus single diuretics, furosemide or mannitol, on cisplatin-induced nephrotoxicity.

Cisplatin (CDDP)-induced nephrotoxicity is a common dose-limiting toxicity, and diuretics are often administered to prevent nephrotoxicity. However, the efficacy and optimal administration of diuretics in preventing CDDP-induced nephrotoxicity remain to be established. This study aimed to evaluate the efficacy of combining furosemide and mannitol to prevent CDDP-induced nephrotoxicity. This was a post-hoc analysis of pooled data from a multicenter, retrospective, observational study, including 396 patients who received one or two diuretics for CDDP-based chemotherapy, compared using propensity score matching. Multivariate logistic regression analyses were used to identify risk factors for nephrotoxicity. There was no significant difference in the incidence of nephrotoxicity between the two groups (22.2% vs. 28.3%, P = 0.416). Hypertension, CDDP dose ≥ 75 mg/m2, and no magnesium supplementation were identified as risk factors for nephrotoxicity, whereas the use of diuretics was not found to be a risk factor. The combination of furosemide and mannitol showed no advantage over a single diuretic in preventing CDDP-induced nephrotoxicity. The renal function of patients receiving CDDP-based chemotherapy (≥ 75 mg/m2) and that of those with hypertension should be carefully monitored. Magnesium supplementation is important for these patients.

Protective effect of coenzyme Q10 in cyclophosphamide-induced kidney damage in rats.

OBJECTIVE: We aimed to investigate the effect of coenzyme q10 on cyclophosphamide-induced kidney damage in rats. METHODS: A total of 30 female Wistar-Albino rats were utilized to form three groups. In group 1 (control group) (n=10), no drugs were given. In group 2 (cyclophosphamide group) (n=10), 30 mg/kg intraperitoneal cyclophosphamide was administered for 7 days. In group 3 (cyclophosphamide+coenzyme q10 group) (n=10), 30 mg/kg cyclophosphamide and 10 mg/kg coenzyme q10 were given for 7 days via intraperitoneal route. Right kidneys were removed in all groups. Blood malondialdehyde levels and activities of catalase and superoxide dismutase were measured. Histopathological damage was evaluated by examining the slides prepared from kidney tissue using a light microscope. RESULTS: Tissue damage was significantly higher in the cyclophosphamide group than in the cyclophosphamide+coenzyme q10 group (p<0.05). The malondialdehyde levels were significantly higher and the activities of superoxide dismutase and catalase were lower in the cyclophosphamide group than in the cyclophosphamide+coenzyme q10 group (p<0.05). CONCLUSION: Coenzyme q10 may be a good option to prevent cyclophosphamide-induced kidney damage.

Development and validation of a nomogram for predicting the occurrence of renal dysfunction after treatment of immune checkpoint inhibitor: a retrospective case-control study.

PURPOSE: The administration of immune checkpoint inhibitors (ICIs) may lead to renal adverse events, notably including renal dysfunction. To early predict the probability of renal dysfunction after ICIs therapy, a retrospective case-control study was conducted. METHODS: Clinical information on ICIs-treated patients was collected. Multivariable logistic regression was applied to identify risk factors for renal dysfunction after ICIs treatment. Moreover, a nomogram model was developed and validated internally. RESULTS: A total of 442 patients were included, among which 35 (7.9%) experienced renal dysfunction after ICIs treatment. Lower baseline estimated glomerular filtration rate (eGFR) (OR 0.941; 95% CI 0.917 to 0.966; p<0.001), concurrent exposure of platinum(OR 4.014; 95% CI 1.557 to 10.346; p=0.004), comorbidities of hypertension (OR 3.478; 95% CI 1.600 to 7.562; p=0.002) and infection (OR 5.402; 95% CI 1.544 to 18.904; p=0.008) were found to be independent associated with renal dysfunction after ICIs treatment. To develop a predictive nomogram for the occurrence of renal dysfunction after ICIs treatment, the included cases were divided into training and validation groups in a ratio of 7:3 randomly. The above four independent risk factors were included in the model. The area under the receiver operating characteristic curves of the predictiive model were 0.822 (0.723-0.922) and 0.815 (0.699-0.930) in the training and validation groups, respectively. CONCLUSIONS: Lower baseline eGFR, platinum exposure, comorbidities of hypertension and infection were predictors of renal dysfunction in ICIs-treated patients with cancer. A nomogram was developed to predict the probability of renal dysfunction after ICIs treatment, which might be operable and valuable in clinical practice.

Effects of adenosine triphosphate, Lacidipine, and Benidipine on 5-fluorouracil-induced kidney damage in rats.

OBJECTIVE: In the present study, the protective effects of adenosine triphosphate (ATP), Benidipine, and Lacidipine on potential kidney damage induced by 5-fluorouracil (5-FU) were investigated in rats. MATERIALS AND METHODS: Totally 48 rats were divided into 8 groups: healthy (HG), 5-FU (FUG), ATP+5-FU (AFU), Benidipine+5-FU (BFU), Lacidipine+5-FU (LFU), ATP+Benidipine+5-FU (ABFU), ATP+Lacidipine+5-FU (ALFU) and Benidipine+Lacidipine+5-FU (BLFU). In a 10-day period, ATP (4 mg/kg) was administered intraperitoneally, and Benidipine (4 mg/kg) and Lacidipine (4 mg/kg) were administered orally once a day. On days 1, 3, and 5, 5-FU (100 mg/kg) was administered intraperitoneally one hour after the drug was administered. Afterward, the rats were euthanized, and kidney tissues were removed. An analysis of malondialdehyde, total glutathione, superoxide dismutase, and catalase was performed on tissues, as well as a histopathological examination. A creatinine and blood urea nitrogen analysis were performed on blood samples. RESULTS: It was revealed that 5-FU decreased the amount of total glutathione, superoxide dismutase, and catalase activities in rat kidney tissues and increased malondialdehyde. Further, increased serum creatinine and blood urea nitrogen levels, as well as histopathological examination of kidney tissues, were found in the 5-FU group. ATP+Benidipine and ATP treatments were the most effective in preventing both biochemical and histopathological changes induced by 5-FU. A treatment with Benidipine improved biochemical and histopathologic data, but not to the same extent as a treatment with ATP+Benidipine and ATP. As a result of Lacidipine+ATP combination, 5-FU-induced biochemical changes in kidney tissue were partially inhibited, but the degree of histopathologic damage remained unchanged. Neither Benidipine+Lacidipine nor Lacidipine showed a protective effect on both biochemical changes and histopathologic damage. CONCLUSIONS: It may be possible to prevent nephrotoxicity by adding ATP + Benidipine or ATP to 5-FU treatment.

Renal macrophages induce hypertension and kidney fibrosis in Angiotensin II salt mice model.

The immune system is involved in hypertension development with different immune cells reported to have either pro or anti-hypertensive effects. In hypertension, immune cells have been thought to infiltrate blood pressure-regulating organs, resulting in either elevation or reduction of blood pressure. There is controversy over whether macrophages play a detrimental or beneficial role in the development of hypertension, and the few existing studies have yielded conflicting results. This study aimed to determine the effects of angiotensin II (Ang II) salt-induced hypertension on renal immune cells and to determine whether renal macrophages are involved in the induction of hypertension. Hypertension was induced by administration of Ang II and saline for two weeks. The effects of hypertension on kidney immune cells were assessed using flow cytometry. Macrophage infiltration in the kidney was assessed by immunohistochemistry and kidney fibrosis was assessed using trichrome stain and kidney real time-qPCR. Liposome encapsulated clodronate was used to deplete macrophages in C57BL/6J mice and investigate the direct role of macrophages in hypertension induction. Ang II saline mice group developed hypertension, had increased renal macrophages, and had increased expression of Acta2 and Col1a1 and kidney fibrotic areas. Macrophage depletion blunted hypertension development and reduced the expression of Acta2 and Col1a1 in the kidney and kidney fibrotic areas in Ang II saline group. The results of this study demonstrate that macrophages infiltrate the kidneys and increase kidney fibrosis in Ang II salt-induced hypertension, and depletion of macrophages suppresses the development of hypertension and decreases kidney fibrosis. This indicates that macrophages play a direct role in hypertension development. Hence macrophages have a potential to be considered as therapeutic target in hypertension management.

Associations among environmental exposure to trace elements and biomarkers of early kidney damage in the pediatric population.

BACKGROUND: In kidney damage, molecular changes can be used as early damage kidney biomarkers, such as Kidney Injury Molecule-1 and Neutrophil gelatinase-associated lipocalin. These biomarkers are associated with toxic metal exposure or disturbed homeostasis of trace elements, which might lead to serious health hazards. This study aimed to evaluate the relationship between exposure to trace elements and early damage kidney biomarkers in a pediatric population. METHODS: In Tlaxcala, a cross-sectional study was conducted on 914 healthy individuals. The participants underwent a medical review and a socio-environmental questionnaire. Five early damage kidney biomarkers were determined in the urine with Luminex, and molybdenum, copper, selenium, nickel, and iodine were measured with ICP-Mass. RESULTS: The eGFR showed a median of 103.75 mL/min/1.73 m2. The median levels for molybdenum, copper, selenium, nickel, and iodine were 24.73 ng/mL, 73.35 ng/mL, 4.78 ng/mL, 83.68 ng/mL, and 361.83 ng/mL, respectively. Except for molybdenum and nickel, the other trace elements had significant associations with the eGFR and the early kidney damage biomarkers. Additionally, we report the association of different exposure scenarios with renal parameters. DISCUSSION: and Conclusions. Among the explored metals, exposure to Cu and iodine impairs renal function. In contrast, Se may manifest as a beneficial metal. Interactions of Mo-Se and Mo-Iodine seem to alter the expression of NGAL; Mo-Cu for CLU; Mo-Cu, Mo-Se, and Mo-iodine for Cys-C and a-1MG; and Mo-Cu and Mo-iodine for KIM-1; were noticed. Our study could suggest that trace element interactions were associated with early kidney damage biomarkers.

Ferulic acid alleviates avermectin induced renal injury in carp by inhibiting inflammation, oxidative stress and apoptosis.

Avamectin (AVM), a macrolide antibiotic, is widely used in fisheries, agriculture, and animal husbandry, however, its irrational use poses a great danger to aquatic organisms. Ferulic acid (FA) is a natural chemical found in the cell walls of plants. It absorbs free radicals from the surrounding environment and acts as an antioxidant. However, the protective effect of FA against kidney injury caused by AVM has not been demonstrated. In this study, 60 carp were divided into the control group, AVM group (2.404 µg/L), FA+AVM group and FA group (400 mg/kg). Pathological examination, quantitative real-time PCR (qPCR), reactive oxygen species (ROS) and western blot were used to evaluate the preventive effect of FA on renal tissue injury after AVM exposure. Histological findings indicated that FA significantly reduced the swelling and infiltration of inflammatory cells in the kidney tissues of carp triggered by AVM. Dihydroethidium (DHE) fluorescent probe assay showed that FA inhibited the accumulation of kidney ROS. Biochemical results showed that FA significantly increased glutathione (GSH) content, total antioxidant capacity (T-AOC) and catalase (CAT) activity, and decreased intracellular malondialdehyde (MDA) content. In addition, western blot results revealed that the protein expression levels of Nrf2 and p-NF-κBp65 in the carp kidney were inhibited by AVM, but reversed by the FA. The qPCR results exhibited that FA significantly increased the mRNA levels of tgf-ß1 and il-10, while significantly down-regulated the gene expression levels of tnf-α, il-6 and il-1ß. These data suggest that FA can reduce oxidative stress and renal tissue inflammation induced by AVM. At the same time, FA inhibited the apoptosis of renal cells induced by AVM by decreasing the transcription level and protein expression level of Bax, and increasing the transcription level and protein expression level of Bcl2, PI3K and AKT. This study provides preliminary evidence for the theory that FA reduces the level of oxidative stress, inflammation response and kidney tissue damage caused by apoptosis in carp, providing a theoretical basis for the prevention and treatment of the AVM.

Opioid-induced respiratory depression suspected of drug interaction in a prostate cancer patient: a case report.

BACKGROUND: Many of the drugs used for the treatment and alleviation of symptoms in cancer patients are known to inhibit or induce cytochrome P450 (CYP). Therefore, it is important to pay attention to the drug interactions of opioid analgesics that are metabolized by CYPs, because for example when using oxycodone metabolized by CYP3A4, it is possible that the effect will be attenuated or enhanced by the concomitant use of drugs that induce or inhibit CYP3A4. Aprepitant, an antiemetic drug used in many patients receiving anticancer drugs, is known as a moderate competitive inhibitor of CYP3A4. We experienced a case of respiratory depression caused by opioids, which was suspected to be caused by a drug interaction with antiemetics especially aprepitant. CASE DESCRIPTION: The patient was a 72-year-old man. He had been treated with continuous oxycodone infusion for perianal pain associated with the rectal invasion of prostate cancer. No comorbidities other than renal dysfunction were observed. Oxycodone treatment was started at 48 mg/day, and was increased to 108 mg/day, and then the pain decreased. Once the pain was controlled, chemotherapy was planned. Antiemetics (dexamethasone, palonosetron, and aprepitant) were administered before anticancer drug administration. Approximately 3 hours after antiemetics administration and before the administration of the anticancer drugs, a ward nurse noticed that oversedation and respiratory depression had occurred. When the patient was called, he immediately woke up and was able to talk normally, so the anticancer drugs were administered as scheduled. About 2 hours after the nurse noticed oversedation, the attending physician reduced the dose of oxycodone infusion to 48 mg/day. After that, his drowsiness persisted, but his respiratory condition improved. Despite reducing the dose of oxycodone to less than half, the pain remained stable at numeric rating scale (NRS) 0-1, without the use of a rescue dose. The patient was discharged from the hospital 36 days after the administration of anticancer drugs, without any problems. CONCLUSIONS: The cause of respiratory depression in this case was thought to be a combination of factors, including drug interactions between oxycodone and antiemetics, and oxycodone accumulation due to renal dysfunction.

Development and Characterization of a Novel FVB-PrkdcR2140C Mouse Model for Adriamycin-Induced Nephropathy.

The Adriamycin (ADR) nephropathy model, which induces podocyte injury, is limited to certain mouse strains due to genetic susceptibilities, such as the PrkdcR2140C polymorphism. The FVB/N strain without the R2140C mutation resists ADR nephropathy. Meanwhile, a detailed analysis of the progression of ADR nephropathy in the FVB/N strain has yet to be conducted. Our research aimed to create a novel mouse model, the FVB-PrkdcR2140C, by introducing PrkdcR2140C into the FVB/NJcl (FVB) strain. Our study showed that FVB-PrkdcR2140C mice developed severe renal damage when exposed to ADR, as evidenced by significant albuminuria and tubular injury, exceeding the levels observed in C57BL/6J (B6)-PrkdcR2140C. This indicates that the FVB/N genetic background, in combination with the R2140C mutation, strongly predisposes mice to ADR nephropathy, highlighting the influence of genetic background on disease susceptibility. Using RNA sequencing and subsequent analysis, we identified several genes whose expression is altered in response to ADR nephropathy. In particular, Mmp7, Mmp10, and Mmp12 were highlighted for their differential expression between strains and their potential role in influencing the severity of kidney damage. Further genetic analysis should lead to identifying ADR nephropathy modifier gene(s), aiding in early diagnosis and providing novel approaches to kidney disease treatment and prevention.

Butylparaben induced zebrafish (Danio rerio) kidney injury by down-regulating the PI3K-AKT pathway.

Butylparaben, a common endocrine disruptor in the environment, is known to be toxic to the reproductive system, heart, and intestines, but its nephrotoxicity has rarely been reported. In order to study the nephrotoxicity and mechanism of butylparaben, we examined the acute and chronic effects on human embryonic kidney cells (HEK293T) and zebrafish. Additionally, we assessed the potential remedial effects of salidroside against butylparaben-induced nephrotoxicity. Our in vitro findings demonstrated oxidative stress and cytotoxicity to HEK293T cells caused by butylparaben. In the zebrafish model, the concentration of butylparaben exposure ranged from 0.5 to 15 µM. An assortment of experimental techniques was employed, including the assessment of kidney tissue morphology using Hematoxylin-Eosin staining, kidney function analysis via fluorescent dextran injection, and gene expression studies related to kidney injury, development, and function. Additionally, butylparaben caused lipid peroxidation in the kidney, thereby damaging glomeruli and renal tubules, which resulted from the downregulation of the PI3K-AKT signaling pathway. Furthermore, salidroside ameliorated butylparaben-induced nephrotoxicity through the PI3K-AKT signaling pathway. This study reveals the seldom-reported kidney toxicity of butylparaben and the protective effect of salidroside against toxicological reactions related to nephrotoxicity. It offers valuable insights into the risks to kidney health posed by environmental toxins.

Cyclosporine-induced kidney damage was halted by sitagliptin and hesperidin via increasing Nrf2 and suppressing TNF-α, NF-κB, and Bax.

Cyclosporine A (CsA) is employed for organ transplantation and autoimmune disorders. Nephrotoxicity is a serious side effect that hampers the therapeutic use of CsA. Hesperidin and sitagliptin were investigated for their antioxidant, anti-inflammatory, and tissue-protective properties. We aimed to investigate and compare the possible nephroprotective effects of hesperidin and sitagliptin. Male Wistar rats were utilized for induction of CsA nephrotoxicity (20 mg/kg/day, intraperitoneally for 7 days). Animals were treated with sitagliptin (10 mg/kg/day, orally for 14 days) or hesperidin (200 mg/kg/day, orally for 14 days). Blood urea, serum creatinine, albumin, cystatin-C (CYS-C), myeloperoxidase (MPO), and glucose were measured. The renal malondialdehyde (MDA), glutathione (GSH), catalase, and SOD were estimated. Renal TNF-α protein expression was evaluated. Histopathological examination and immunostaining study of Bax, Nrf-2, and NF-κB were performed. Sitagliptin or hesperidin attenuated CsA-mediated elevations of blood urea, serum creatinine, CYS-C, glucose, renal MDA, and MPO, and preserved the serum albumin, renal catalase, SOD, and GSH. They reduced the expressions of TNF-α, Bax, NF-κB, and pathological kidney damage. Nrf2 expression in the kidney was raised. Hesperidin or sitagliptin could protect the kidney against CsA through the mitigation of oxidative stress, apoptosis, and inflammation. Sitagliptin proved to be more beneficial than hesperidin.

Red Yeast Rice and Statin Therapy in Patients with Hypercholesterolemia and the Comorbidities: A Retrospective Cohort Study on Lipid-Lowering Effects and Cardiovascular Outcomes.

Red yeast rice (RYR) is known for its lipid-lowering effects in patients with hypercholesterolemia; however, its comparative efficacy with statins and risk reduction remains uncertain. This retrospective study analyzed data from 337,104 patients with hyperlipidemia in the Chang Gung Research Database cohort, spanning from January 2016 to December 2021. Exclusion criteria were applied to ensure data completeness and compliance, including an age limit of [Formula: see text] years, absence of RYR or statin treatment, and a treatment duration of [Formula: see text] days. Propensity score matching was employed to minimize bias based on baseline factors, with one patient matching with four patients in the comparison group. The study encompassed a total of 5,984 adult hyperlipidemic patients, with 1,197 in the RYR group and 4,787 in the statin group. The patients were also stratified into statin ([Formula: see text]) or combined use ([Formula: see text]) groups for further comparison. Following one year of treatment, both the RYR and statin groups exhibited reductions in total cholesterol and triglyceride levels. Most biochemical parameters showed no significant differences, except for elevated glutamic oxaloacetic transaminase levels in the RYR group ([Formula: see text]) and increased glycohemoglobin levels in the statin group at the three-month mark ([Formula: see text]). In patients with comorbid diabetes, hypertension, kidney, or liver diseases, RYR and statins demonstrated comparable risks for emergency room (ER) visits, stroke, and myocardial infarction (MI). However, the combination of RYR and statins was associated with reduced stroke-related hospitalizations in patients with diabetes, hypertension, and kidney disease, as well as decreased MI-related hospitalizations in patients with hypertension and kidney disease (all [Formula: see text]). In conclusion, both RYR and statins effectively lower blood lipid levels and mitigate related complications. Combining these therapies may lead to fewer ER visits, reduced stroke frequency, and fewer MI hospitalizations in hypertensive and kidney disease patients, and they decreased all-cause mortality in the kidney disease population. Further research on combined therapy is warranted.

Tropical postbiotics alleviate the disorders in the gut microbiota and kidney damage induced by ochratoxin A exposure.

Ochratoxin A (OTA), commonly found in various foods, significantly impacts the health of humans and animals, especially their kidneys. Our study explores OTA's effects on the gut microbiota and kidney damage while examining how postbiotics offer protection. Using metagenomic sequencing, we observed that OTA increased the potential gut pathogens such as Alistipes, elevating detrimental metabolites and inflammation. Also, OTA inhibited the Nrf2/HO-1 pathway, reducing kidney ROS elimination and leading to cellular ferroptosis and subsequent kidney damage. Postbiotics mitigate OTA's effects by downregulating the abundance of the assimilatory sulfate reduction IV pathway and virulence factors associated with iron uptake and relieving the inhibition of OTA on Nrf2/HO-1, restoring ROS-clearing capabilities and thereby alleviating chronic OTA-induced kidney damage. Understanding the OTA-gut-kidney link provides new approaches for preventing kidney damage, with postbiotics showing promise as a preventive treatment.

Ototoxic and nephrotoxic drugs in neonatal intensive care units: results of a Spanish and Italian survey.

Neonates face heightened susceptibility to drug toxicity, often exposed to off-label medications with dosages extrapolated from adult or pediatric studies. Premature infants in Neonatal Intensive Care Units (NICUs) are particularly at risk due to underdeveloped pharmacokinetics and exposure to multiple drugs. The study aimed to survey commonly used medications with a higher risk of ototoxicity and nephrotoxicity in Spanish and Italian neonatal units. A prospective cross-sectional study was conducted in Italian and Spanish neonatal units using a web-based survey with 43 questions. A modified Delphi method involved experts refining the survey through online consensus. Ethical approval was obtained, and responses were collected from January to July 2023. The survey covered various aspects, including drug-related ototoxic and nephrotoxic management, hearing screening, and therapeutic drug monitoring. Responses from 131 participants (35.9% from Spain and 64.1% from Italy) revealed awareness of drug toxicity risks. Varied practices were observed in hearing screening protocols, and a high prevalence of ototoxic and nephrotoxic drug use, including aminoglycosides (100%), vancomycin (70.2%), loop diuretics (63.4%), and ibuprofen (62.6%). Discrepancies existed in guideline availability and adherence, with differences between Italy and Spain in therapeutic drug monitoring practices. CONCLUSIONS: The study underscores the need for clinical guidelines and uniform practices in managing ototoxic and nephrotoxic drugs in neonatal units. Awareness is high, but inconsistencies in practices indicate a necessity for standardization, including the implementation of therapeutic drug monitoring and the involvement of clinical pharmacologists. Addressing these issues is crucial for optimizing neonatal care in Southern Europe. WHAT IS KNOWN: • Neonates in intensive care face a high risk of nephrotoxicity and ototoxicity from drugs like aminoglycosides, vancomycin, loop diuretics, and ibuprofen. • Therapeutic drug monitoring is key for managing these risks, optimizing dosing for efficacy and minimizing side effects. WHAT IS NEW: • NICUs in Spain and Italy show high drug toxicity awareness but differ in ototoxic/nephrotoxic drug management. • Urgent need for standard guidelines and practices to address nephrotoxic risks from aminoglycosides, vancomycin, loop diuretics, and ibuprofen.