Nephrotoxicity Research Articles

The Role of Biphosphonate and Denosumab in Bone Metastasis

Metastasis is a major contributor to cancer-related morbidity and mortality. Bone metastasis is prevalent and associated with pain and fractures, particularly in breast cancer where up to 80% of patients may be affected. Bisphosphonates, traditional anti-resorptive drugs, have been crucial in managing bone metastatic cancers. This article reviews the pathophysiology of bone metastasis, focusing on the invasion-metastasis cascade and the role of matrix metalloproteinases (MMPs). The formation of metastatic tissue in bones involves disrupting the balance of the bone remodeling process. The study delves into the three generations of bisphosphonates, elucidating their structural differences and mechanisms of action. First-generation bisphosphonates, such as etidronate and clodronate, lack nitrogen and interfere with cellular processes. Second-generation bisphosphonates, including alendronate and pamidronate, bind to nitrogen and inhibit farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway. Third-generation bisphosphonates like risedronate and zoledronate have a heterogeneous nitrogenous chain, enhancing anti-resorptive activity. Denosumab's distinct pharmacokinetics and potential risks upon discontinuation are discussed. The article emphasizes the need for clinicians to be vigilant about potential adverse effects, especially kidney toxicity with bisphosphonates, and to tailor treatment based on individual patient characteristics.

Outpatient Laboratory Monitoring for Antibiotic-related Adverse Events in Children With Acute Hematogenous Osteomyelitis.

Monitoring for antibiotic-related lab abnormalities (ARLA), including hematologic, renal, and/or hepatic toxicity, in pediatric osteomyelitis is common. In 240 cases of osteomyelitis with outpatient laboratory monitoring, ARLA occurred in 13.3% with the most common finding being neutropenia. ARLA impacted antibiotic therapy in <1% of subjects, however, raising questions about the value of such monitoring being performed routinely.

Vernonia amygdalina, Ocimum gratissimum and Talinum triangulare Mitigates Kidney Toxicity in Male Wistar Rats Administered with Dichlorvos

This study aimed to evaluate the therapeutic potentials of extracts from medicinal plants (Vernonia amygdalina, Ocimumgratissimum, Talinum triangulare) against DDVP-induced renal toxicity in Wistar rats. A total of 50 male adult rats, each weighing approximately 272g, were divided into ten groups (n=5). The groups were given normal saline (normal control), 8.0mg/kg body weight DDVP (positive control), 8.0mg/kg body weight DDVP along with 200mg/kg and 400mg/kg body weight of the plant extracts respectively, and 20mg/kg and 40mg/kg body weight of vitamin C for 28 days. DDVP significantly (P&lt;0.05) increased urea, creatinine, Na+, K+, Cl-, and significantly (P&lt;0.05) decreased HCO3- compared to the normal control. Treatment with the aqueous leaf extracts of Vernonia amygdalina, Ocimumgratissimum, and Talinum triangulare significantly corrected these biochemical imbalances when contrasted with the positive control. Histology of the kidney tissues supported these findings. In conclusion, the aqueous leaf extracts of Vernonia amygdalina, Ocimumgratissimum, and Talinum triangulare may have therapeutic potential against DDVP-induced renal toxicity in rats.

Modulatory Effect of Ginseng Extracts against Trafos Cu Plant Growth Regulators Induced Renal Toxicity in Rats

Modulatory Effect of Ginseng Extracts against Trafos Cu Plant Growth Regulators Induced Renal Toxicity in Rats

New insights into zinc alleviating renal toxicity of arsenic-exposed carp (Cyprinus carpio) through YAP-TFR/ROS signaling pathway

Environmental pollution caused by arsenic or its compounds is called arsenic pollution. Arsenic pollution mainly comes from people mining and smelting arsenic compounds. In addition, arsenic compounds' widespread use and production of arsenic-containing pesticides, arsenic-rich water used to irrigate farms, or high arsenic levels in foods caused by coal burning are all sources of arsenic contamination. Arsenic contamination poses a significant threat to global public health. It is reported that exposure to arsenic can induce severe renal injury. However, the underlying mechanism needs to be clarified. In this study, the arsenic exposure model in vivo and in vitro was used to explore the mechanism of arsenic-induced renal injury, especially the role of ferroptosis and its regulatory mechanism, and then to evaluate its anti-pollution effect by supplementing zinc. The results showed that arsenic significantly induced ferroptosis, characterized by up-regulating the expression of YAP and TFR in kidney and CIK cells and then increasing the levels of Fe2+ and ROS, lipid peroxidation, and iron metabolism. Microscopic observation revealed the shrinkage of mitochondria and the increase in membrane density. In addition, molecular docking and inhibitor experiments further confirmed that arsenic is involved in the process of ferroptosis by activating YAP and TFR. These results clarify the harmful effects of arsenic on carp kidneys and its mechanism and highlight the critical interactions between the YAP-TFR pathway, ROS, and ferroptosis. Importantly, this study found that zinc can reduce ferroptosis caused by the arsenic-activated YAP-TFR pathway by inhibiting YAP activation and lipid peroxidation.

Thyroid, neurodevelopmental, and kidney toxicities of common organic UV filters in embryo-larval zebrafish (Danio rerio), and their potential links

Organic UV filters (OUVFs) have been commonly used in sunscreen and many consumer products. Following dermal application, these compounds can enter circulation and may cause systemic effects in humans. In the present study, we chose four OUVFs frequently detected in the environment, i.e., avobenzone (AVB), benzophenone-3 (BP-3), octocrylene (OC), and octyl methoxycinnamate (OMC), and evaluated their thyroid, neurodevelopmental, and kidney toxicities. For this purpose, zebrafish embryos (<4 h post fertilization, hpf) were exposed to sublethal concentrations of AVB, BP-3, OC, or OMC until 120 hpf. Exposure to all OUVFs decreased thyroid hormone (TH) levels, probably by enhanced metabolism and excretion of THs (ugt1ab and/or sult1 st5) in the larval fish. Exposure to the OUVFs also induced hypoactivities and/or anxiety-like behaviors: Regulatory changes of mbp, gfap, c-fos, syn2a, sty1a, and stxbp1b genes, support the changes in normal neurobehavior of the larval fish. Moreover, the OUVFs exposure caused increased proteinuria in the fish, along with transcriptional changes of wt1, nephrin, podocin, and cdh17 genes, which could explain the observed reduction in kidney functions. Principal component analysis (PCA) implied the potential interplay of THs with neurogenesis, or podocyte differentiation of the larval fish. Toxicological consequences of altered TH homeostasis, neurobehavior, and kidney function at the early life stage warrant further investigations not only in humans but also in aquatic ecosystems.

The IDH1-R132H mutation aggravates cisplatin-induced acute kidney injury by promoting ferroptosis through disrupting NDUFA1 and FSP1 interaction

AbstractThe IDH1-R132H mutation is implicated in the development of various tumors. Whether cisplatin, a common chemotherapeutic agent, induces more significant renal toxicity in individuals with the IDH1-R132H mutation remains unclear. In this study, we observed that the IDH1-R132H mutation exacerbates mitochondrial lipid peroxidation and dysfunction in renal tubules, rendering the kidneys more susceptible to cisplatin-induced ferroptosis. The IDH1-R132H mutation increases methylation of the Ndufa1 promoter, thereby suppressing NDUFA1 transcription and translation. This suppression disrupts NDUFA1’s interaction with FSP1, reducing its resistance to cisplatin-induced tubular epithelial cell death. As a consequence, ROS accumulates, lipid peroxidation occurs, and ferroptosis is triggered, thereby promoting acute kidney injury. In summary, this study elucidates a novel mechanism underlying cisplatin-induced nephrotoxicity and provides valuable insights for the development of personalized treatment strategies for tumor patients carrying the IDH1-R132H mutation.

Retinal ischemia-reperfusion injury and pretreatment with Lycium barbarum glycopeptide.

To investigate the antioxidant protective effect of Lycium barbarum glycopeptide (LbGP) pretreatment on retinal ischemia-reperfusion (I/R) injury (RIRI) in rats. RIRI was induced in Sprague Dawley rats through anterior chamber perfusion, and pretreatment involved administering LbGP via gavage for 7d. After 24h of reperfusion, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (CREA) levels, retinal structure, expression of Caspase-3 and Caspase-8, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) in the retina were measured. The pretreatment with LbGP effectively protected the retina and retinal tissue from edema and inflammation in the ganglion cell layer (GCL) and nerve fiber layer (NFL) of rats subjected to RIRI, as shown by light microscopy and optical coherence tomography (OCT). Serum AST was higher in the model group than in the blank group (P=0.042), but no difference was found in ALT, AST, and CREA across the LbGP groups and model group. Caspase-3 expression was higher in the model group than in the blank group (P=0.006), but no difference was found among LbGP groups and the model group. Caspase-8 expression was higher in the model group than in the blank group (P=0.000), and lower in the 400 mg/kg LbGP group than in the model group (P=0.016). SOD activity was lower in the model group than in the blank group (P=0.001), and the decrease was slower in the 400 mg/kg LbGP group than in the model group (P=0.003). MDA content was higher in the model group than in the blank group (P=0.001), and lower in the 400 mg/kg LbGP group than in the model group (P=0.016). The pretreatment with LbGP did not result in any observed liver or renal toxicity in the model. LbGP pretreatment exhibits dose-dependent anti-inflammatory, and antioxidative effects by reducing Caspase-8 expression, preventing declines of SOD activity, and decreasing MDA content in the RIRI rat model.

Ameliorating Effect of Grape (Vitis vinifera L.) Seed and Peel Extracts with Selenium on Ochratoxin-A Exposed Renal Dysfunction in Male Wistar Rats

Background and AimDrug-induced nephrotoxicity is extensively documented as the initial stage of kidney disease that particularly results in acute renal injury and chronic renal dysfunction. The single and combined effect of grape peel extract (GPE), grape seed extracts (GSE) and selenium (Sel) were investigated in current study for controlling of renal injury induced by Ochratoxin-A (OTA) in male rats. MethodsForty nine male Wistar rats weighing 200 ± 10 g were injected with OTA (0.5 mg/kg bw) to induce nephrotoxicity, then treated with singleand combined applications of GSE, GPE and Sel. In addition, the OTA induced nephrotoxicity rats were screened for various biological and physiological parameters like food ingestion, body weight gain, liver weight, serum kidney biomarkers, serum lipid fractions, enzymatic and non-enzymatic lipid peroxidation indicators and histopathological studies. ResultsOur findings suggested that the combination of GSE 2 % and Sel (50–50) treatment reduced renal dysfunction in OTA-induced rats by significantly lowering lipid peroxidation indicators, lipid and kidneys profiles and enhancing enzymatic and non-enzymatic antioxidants biomarkers followed by GSE 2 % then Selenium (0.4 mg/kg) in OTA. Histological analysis of the kidney revealed more severe renal tubule degeneration in OTA-induced rats, While GSE and GPE combonation showed only moderate glomerular tuft enlargement and minimal renal tubule deterioration. Furthermore, the combination of GSE 2 %+Sel (50–50) revealed normal histological structure. ConclusionsGrape seed extracts along with selenium mightbe used as dietary supplements to reduce renal toxicity induced by chemicals or compounds that cause nephrotoxicity.

Volumetric modulated arc therapy total body irradiation improves toxicity outcomes compared to 2D total body irradiation.

Volumetric modulated arc therapy (VMAT) total body irradiation (TBI) allows for greater organ sparing with improved target coverage compared to 2D-TBI. However, there is limited evidence of whether improved organ sparing translates to decreases in toxicities and how its toxicities compare to those of the 2D technique. We aimed to compare differences in toxicities among patients treated with TBI utilizing VMAT and 2D techniques. A matched-pair single-institution retrospective analysis of 200 patients treated with TBI from 2014 to 2023 was performed. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method and compared using log-rank tests. Differences in characteristics and toxicities between the VMAT and 2D cohorts were compared using Fisher's exact test. Of the 200 patients analyzed, 100 underwent VMAT-TBI, and 100 underwent 2D-TBI. The median age for VMAT-TBI and 2D-TBI patients was 13.7 years and 16.2 years, respectively (p = 0.25). In each cohort, 53 patients were treated with myeloablative regimens (8-13.76 Gy), and 47 were treated with non-myeloablative regimens (2-4 Gy). For the entire VMAT-TBI cohort, lung Dmean, kidney Dmean, and lens Dmax were spared to 60.6% ± 5.0%, 71.0% ± 8.5%, and 90.1% ± 3.5% of prescription, respectively. For the non-myeloablative VMAT-TBI cohort, testis/ovary Dmax, brain, and thyroid Dmean were spared to 33.4% ± 7.3%, 75.4% ± 7.0%, and 76.1% ± 10.5%, respectively. For 2D-TBI, lungs were spared using partial-transmission lung blocks for myeloablative regimens. The VMAT-TBI cohort experienced significantly lower rates of any grade of pneumonitis (2% vs. 12%), nephrotoxicity (7% vs. 34%), nausea (68% vs. 81%), skin (16% vs. 35%), and graft versus host disease (GVHD) (42% vs. 62%) compared to 2D-TBI patients. For myeloablative regimen patients, rates of pneumonitis (0% vs. 17%) and nephrotoxicity (9% vs. 36%) were significantly lower with VMAT-TBI versus 2D-TBI (p < 0.01). Median follow-up was 14.3 months, and neither median OS nor PFS for the entire cohort was reached. In the VMAT versus 2D-TBI cohort, the 1-year OS was 86.0% versus 83.0% (p = 0.26), and the 1-year PFS was 86.6% and 80.0% (p = 0.36), respectively. Normal tissue sparing with VMAT-TBI compared to the 2D-TBI translated to significantly lower rates of pneumonitis, renal toxicity, nausea, skin toxicity, and GVHD in patients, while maintaining excellent disease control.

Investigating the relationship of co-exposure to multiple metals with chronic kidney disease: An integrated perspective from epidemiology and adverse outcome pathways

Systematic studies on the associations between co-exposure to multiple metals and chronic kidney disease (CKD), as well as the underlying mechanisms, remain insufficient. This study aimed to provide a comprehensive perspective on the risk of CKD induced by multiple metal co-exposures through the integration of occupational epidemiology and adverse outcome pathway (AOP). The study participants included 401 male mine workers whose blood metal, β2-microglobulin (β2-MG), and cystatin C (Cys-C) levels were measured. Generalized linear models (GLMs), quantile g-computation models (qgcomp), least absolute shrinkage and selection operator (LASSO), and bayesian kernel machine regression (BKMR) were utilized to identify critical nephrotoxic metals. The mean concentrations of lead, cadmium, mercury, arsenic, and manganese were 191.93, 3.92, 4.66, 3.11, 11.35, and 16.33 µg/L, respectively. GLM, LASSO, qgcomp, and BKMR models consistently identified lead, cadmium, mercury, and arsenic as the primary contributors to kidney toxicity. Based on our epidemiological analysis, we used a computational toxicology method to construct a chemical-genetic-phenotype-disease network (CGPDN) from the Comparative Toxicogenomics Database (CTD), DisGeNET, and GeneCard databases, and further linked key events (KEs) related to kidney toxicity from the AOP-Wiki and PubMed databases. Finally, an AOP framework of multiple metals was constructed by integrating the common molecular initiating events (reactive oxygen species) and KEs (MAPK signaling pathway, oxidative stress, mitochondrial dysfunction, DNA damage, inflammation, hypertension, cell death, and kidney toxicity). This is the first AOP network to elucidate the internal association between multiple metal co-exposures and CKD, providing a crucial basis for the risk assessment of multiple metal co-exposures.

Protective and Therapeutic Effects of Medicinal Plants Against Food Additive-Induced Toxicity.

For thousands of years, people have used medicinal plants and in many parts of the world, traditional medicines continue to play a significant role in the standard treatment of a wide range of illnesses. With changes in modern eating patterns, there has recently been an increase in the use of processed foods. Furthermore, the use of food additives has increased in tandem with the production of processed foods. The dosage levels used for these additives are determined using empirical analyses. However, some additives have demonstrated long-term toxic effects on the human body in toxicity tests. Plants are one of the main sources of biologically active substances and in recent years, many studies have focused on the health benefits of phytochemicals and plant-derived extracts in the treatment and prevention of food additive toxicity. This review clarified studies on several medicinal plants, such as &lt;i&gt;Physalis peruviana&lt;/i&gt; L., &lt;i&gt;Jatropha tanjorensis&lt;/i&gt;, &lt;i&gt;Cymbopogon citratus&lt;/i&gt;,&lt;i&gt; Ficus carica&lt;/i&gt;, &lt;i&gt;Rosmarinus officinalis&lt;/i&gt; L. and others. The findings presented here demonstrate these plants' efficiency and success in preventing and lowering the toxicity of food additives through antioxidant activity reducing oxidative stress, and reduction in renal and hepatic toxicity. Therefore, these plant extracts have a preventive and therapeutic effect in reducing toxicity and may be the best option for reducing the toxicity of food additives in the future. Moreover, additional research is required to confirm the biologically active components found in medicinal plants that are effective in reducing this toxicity.

Single-cell RNA sequencing analysis of peripheral blood mononuclear cells in PD-1-induced renal toxicity in patients with lung cancer

BackgroundAlthough the patient survival rate for many malignancies has been improved with immune checkpoint inhibitors (ICIs), some patients experience various immune-related adverse events (irAEs). IrAEs impact several organ systems, including the kidney. With anti-programmed cell death protein 1 (PD-1) therapy (pembrolizumab), kidney-related adverse events occur relatively rarely compared with other irAEs. However, the occurrence of AKI usually leads to anti-PD-1 therapy interruption or discontinuation. Therefore, there is an urgent need to clarify the mechanisms of renal irAEs (R-irAEs) to facilitate early management. This study aimed to analyse the characteristics of peripheral blood mononuclear cells (PBMCs) in R-irAEs.MethodsPBMCs were collected from three patients who developed R-irAEs after anti-PD-1 therapy and three patients who did not. The PBMCs were subjected to scRNA-seq to identify cell clusters and differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses were performed to investigate the most active biological processes in immune cells.ResultsFifteen cell clusters were identified across the two groups. FOS, RPS26, and JUN were the top three upregulated genes in CD4+ T cells. The DEGs in CD4+ T cells were enriched in Th17 differentiation, Th1 and Th2 cell differentiation, NF-kappa B, Nod-like receptor, TNF, IL-17, apoptosis, and NK cell-mediated cytotoxicity signaling pathways. RPS26, TRBV25-1, and JUN were the top three upregulated genes in CD8+ T cells. The DEGs in CD8+ T cells were enriched in Th17 cell differentiation, antigen processing and presentation, natural killer cell-mediated cytotoxicity, the intestinal immune network for IgA production, the T-cell receptor signalling pathway, Th1 and Th2 cell differentiation, the phagosome, and cell adhesion molecules.ConclusionsIn conclusion, R-irAEs are associated with immune cell dysfunction. DEGs and their enriched pathways identified in CD4+ T cells and CD8+ T cells play important roles in the development of renal irAEs related to anti-PD-1 therapy. These findings offer fresh perspectives on the pathogenesis of renal damage caused by anti-PD-1 therapy.

Survival impact of [225Ac]Ac-DOTATOC alpha-therapy in a preclinical model of pancreatic neuroendocrine tumor liver micrometastases.

A mouse model of liver metastases of pancreatic NETs was developed by intraportal injection of AR42J cells and explored using [68Ga]Ga-DOTATOC and [18F]F-FDG PET/MRI. Biodistribution study and radiation dosimetry of [225Ac]Ac-DOTATOC were determined in subcutaneous tumor-bearing NMRI-nude mice. Efficacy and toxicity were determined by intravenous injection of increasing activities of [225Ac]Ac-DOTATOC 10days after intraportal graft. Liver tumors showed a high uptake of [68Ga]Ga-DOTATOC and no uptake of [18F]F-FDG confirming the well-differentiated phenotype. All groups treated with [225Ac]Ac-DOTATOC showed a significant increase in overall survival compared with DOTATOC-treated mice, especially those treated with the highest activities: 53days with 240kBq (p = 0.0001), and 58days with 2 × 120kBq (p < 0.0001) vs 28days with non-radiolabeled DOTATOC. On blood tests, a transient and moderate decreased in white blood cells count after treatment and no severe hepatic or renal toxicity were observed after treatment which was consistent with pathological and radiation dosimetry findings. [225Ac]Ac-DOTATOC exhibit a favorable efficacy and toxicity profile in a mouse model of liver micrometastatic pancreatic NET.

Topical vancomycin powder for the prevention of surgical site infections in spinal deformity surgery: a systematic review and meta-analysis.

To assess the effectiveness and safety of topical vancomycin powder (VP) in preventing surgical site infections (SSIs) in spinal deformity surgeries. A literature search was conducted on Web of Science, PubMed, and Cochrane Library databases for comparative studies of VP in spinal deformity surgeries published before February 2024. Two reviewers independently screened eligible articles based on the inclusion and exclusion criteria, assessed study quality, and extracted data. Data analysis was performed using Review Manager 5.4 software. Of all 143 papers screened, a meta-analysis was conducted on 10 articles, which included a total of 8,166 surgeries. The results of the meta-analysis indicated that the incidence of deep SSI in VP group was 0.28 times that in non-VP group (p < 0.001). In the subgroup analysis, VP treatment significantly reduced the risk of deep SSI in both adult spinal deformity (ASD) (RR 0.40, 95% CI 0.21-0.77, p = 0.006) and pediatric scoliosis (PS) (RR 0.25, 95% CI 0.16-0.38, p < 0.001) surgeries. However, this effect was not observed in neuromuscular scoliosis (NMS) patients (RR 0.66, 95% CI 0.26-1.66, p = 0.38). Bacterial culture results indicated that VP treatment significantly reduced polymicrobial infections (p = 0.007) and gram-positive infections (p = 0.001). From the literature available at present, VP was associated with reduced deep SSIs rates in spinal deformity patients. However, particular attention should be paid to the lack of the effectiveness of VP in NMS patients. The current literature did not report local cytotoxicity or renal toxicity related to VP in spinal deformity patients.

Unraveling the mechanism of quercetin alleviating BHPF-induced apoptosis in epithelioma papulosum cyprini cells: SIRT3-mediated mitophagy

Fluorene-9-bisphenol (BHPF), as an alternative to bisphenol A, is now increasingly used in plastic products. The accumulation of BHPF in the water environment has posed potential safety risks to aquatic organisms. Unfortunately, the toxicity of BHPF on the physiological metabolism of aquatic animals remains unclear, especially on the molecular mechanisms of BHPF kidney toxicity and antagonizing BHPF toxicity. Quercetin (QCT), a naturally occurring flavonoid, has been reported to mitigate the toxic effects on aquatic organisms induced by a variety of environmental contaminants. It is unclear whether QCT can be a candidate for mitigating BHPF toxicity. In this study, we investigated the protective effect of QCT on BHPF-induced apoptosis and elucidated the possible mechanism of the protective effect mediated by QCT. We treated epithelioma papulosum cyprini cells (EPCs) with 20 μM of BHPF and/or 20 μM of QCT, and the results showed that BHPF significantly increased the release of reactive oxygen species (ROS) from EPCs, decreased the expression of SIRT3, and initiated endogenous apoptosis. Molecular docking provides evidence for the interaction of QCT and SIRT3. Our intervention with Honokiol (HKL) showed that QCT or HKL treatment significantly attenuated BHPF-induced mitochondrial dysfunction and mitochondrial apoptosis (mtApoptosis) in EPCs, and activated mitophagy, restoring autophagy flux. To further investigate the specific mechanism of the protective effect of QCT, we intervened with Cyclosporin A (CsA), and our results suggest that QCT activation of SIRT3-promoted regulation of mitophagy may be a therapeutic strategy to attenuate the toxic effects of BHPF on EPCs. In conclusion, our findings suggest that BHPF induces oxidative damage and mtApoptosis in EPCs and that QCT activates mitophagy and improves autophagic flux through activation of SIRT3, thereby alleviating apoptosis mediated by mitochondrial dysfunction in EPCs. Our study provides a theoretical basis for reassessing the safety of BHPF for aquatic organisms and reveals a novel detoxification mechanism against the toxic effects of BHPF.

Synergistic Enhancement of 5-Fluorouracil Chemotherapeutic Efficacy by Taurine in Colon Cancer Rat Model.

Colorectal cancer (CRC) is one of the top 10 most common cancers worldwide and caused approximately 10 million deaths in 2022. CRC mortality has increased by 10% since 2020 and 52.000 deaths will occur in 2024, highlighting the limitations of current treatments due to ineffectiveness, toxicity, or non-adherence. The widely used chemotherapeutic agent, 5-fluorouracil (5-FU), is associated with several adverse effects, including renal, cardiac, and hepatic toxicity; mucositis; and resistance. Taurine (TAU), an essential β-amino acid with potent antioxidant, antimutagenic, and anti-inflammatory properties, has demonstrated protective effects against tissue toxicity from chemotherapeutic agents like doxorubicin and cisplatin. Taurine deficiency is linked to aging and cancers such as breast and colon cancer. This study hypothesized that TAU may mitigate the adverse effects of 5-fluorouracil (5-FU). Carcinogenesis was chemically induced in rats using 1,2-dimethylhydrazine (DMH). Following five months of cancer progression, taurine (100 mg/kg) was administered orally for 8 days, and colon tissues were analyzed. The results showed 80% of adenocarcinoma (AC) in DMH-induced control animals. Notably, the efficacy of 5-FU showed 70% AC and TAU 50% while, in the 5-FU + TAU group, no adenocarcinoma was observed. No differences were observed in the inflammatory infiltrate or the expression of genes such as K-ras, p53, and Ki-67 among the cancer-induced groups whereas APC/β-catenin expression was increased in the 5FU + TAU-treated group. The mitotic index and dysplasia were increased in the induced 5-FU group and when associated with TAU, the levels returned to normal. These data suggest that 5-FU exhibits a synergic anticancer effect when combined with taurine.

A comparison of the potential of melatonin and tryptophan to ameliorate CCl4-induced hepatic and renal toxicity in Wistar rats

CCl4 causes oxidative injury, fatty degeneration, fibrosis of the liver, renal failure, and even hepatocellular and renal carcinoma. Certain substances have the potential to neutralize the harmful effects of CCl4, so it will lead to numerous beneficial effects. Melatonin (MEL) is a powerful antioxidant that regulates circadian rhythm and has beneficial effects on organism; tryptophan (TRP) is its precursor necessary for the synthesis of MEL. The aim of the current study was to determine whether MEL and TRP, have protective effects during subchronic application of CCl4 to the liver and kidneys. Results suggest that CCl4 led to decrease of total proteins, albumins, globulins, erythrocytes, hemoglobin, and hematocrit; and increase of creatinine, AST, ALT values, and leukocytes. MEL and TRP both showing protective effects on regulation of serum proteins, albumins, globulins, A/G, AST, ALT, and creatinine levels. TRP had been shown to have potential in regulation of disbalanced hematological parameters caused by CCl4. TRP had beneficial effects on hepatocyte morphology in term of beaded chromatin and preserved cell morphology. Overall, oral supplementation of TRP had better protective effects on liver/kidneys compared to MEL.

Effects of orange juice intake on Doxorubicin-induced hepatotoxicity and nephrotoxicity in Wistar rats

Considering that doxorubicin (DOXO) is an anticancer agent with severe adverse effects, this preclinical study investigated the protective effect of ‘pera’ orange juice (POJ) intake on DOXO-induced hepatic and renal toxicities. To this end, male Wistar rats were treated with DOXO in chronic (4.0 mg/kg weekly for four weeks) and acute (16.0 mg/kg in the fourth week) regimens. The experimental groups received filtered water or pasteurized POJ. After euthanasia, livers and kidneys were evaluated histologically and immunohistochemically for Ki-67 and histone γ-H2A.X markers, and their data were analyzed by One-Way ANOVA followed by Tukey’s a posteriori test. In this way, it was observed that DOXO caused weight loss, histological changes and increased damage markers. POJ reduced these changes only in chronic treatment, which allows us to conclude that the orange juice may attenuate the hepatotoxicity and nephrotoxicity of DOXO at low and fractionated doses.

Continuous Versus Intermittent Vancomycin Infusions for Coagulase-negative Staphylococcus Bacteremia in Neonates: A Propensity-matched Cohort Study.

Coagulase-negative staphylococci (CONS) are a major cause of late-onset neonatal sepsis, particularly in preterm infants, with high morbidity and mortality. While vancomycin is the first-line treatment for these infections, the optimal administration in neonates remains uncertain. We aim to compare the outcomes of neonates with CONS bacteremia treated with adjusted continuous infusion (CIV) versus standard intermittent infusion (IIV) of vancomycin. This retrospective study included 110 neonates, with 29 in the CIV group and 47 in the IIV group after propensity score matching. The primary outcome was treatment failure defined by the persistence of a positive blood culture for the same organism after at least 48 hours of vancomycin treatment. After matching, the CIV group exhibited significantly lower treatment failure rates [5/29 (17%) vs. 26/47 (44%); P = 0.014] and a higher rate of achieving therapeutic vancomycin levels after 24 hours [20/29 (69%) vs. 26/47 (44%); P = 0.002] compared to the IIV group. No significant differences were observed in terms of acute kidney failure between the 2 groups. Adjusted continuous vancomycin infusion in neonates with CONS bacteremia is associated with a lower treatment failure rate without an increase in renal toxicity compared to standard intermittent infusion. However, due to the observational design, larger prospective studies are needed to validate these results.