Nephrotoxicity Research Articles

Hematological and renal toxicity in mice after three cycles of high activity [177Lu]Lu-PSMA-617 with or without human α1-microglobulin

Radioligand therapy with [177Lu]Lu-PSMA-617 can be used to prolong life and reduce tumor burden in terminally ill castration resistant prostate cancer patients. Still, accumulation in healthy tissue limits the activity that can be administered. Therefore, fractionated therapy is used to lower toxicity. However, there might be a need to reduce toxicity even further with e.g. radioprotectors. The aim of this study was to (i). establish a preclinical mouse model with fractionated high activity therapy of three consecutive doses of 200 MBq [177Lu]Lu-PSMA-617 in which we aimed to (ii). achieve measurable hematotoxicity and nephrotoxicity and to (iii). analyze the potential protective effect of co-injecting recombinant α1-microglobulin (rA1M), a human antioxidant previously shown to have radioprotective effects. In both groups, three cycles resulted in increased albuminuria for each cycle, with large individual variation. Another marker of kidney injury, serum blood urea nitrogen (BUN), was only significantly increased compared to control animals after the third cycle. The number of white and red blood cells decreased significantly and did not reach the levels of control animals during the experiment. rA1M did reduce absorbed dose to kidney but did not show significant protection here, but future studies are warranted due to the recent clinical studies showing a significant renoprotective effect in patients.

Pre-treatment assessment of chemotherapy for cancer patients: a multi-site evidence implementation project of 74 hospitals in China

BackgroundChemotherapy, whilst treating tumours, can also lead to numerous adverse reactions such as nausea and vomiting, fatigue and kidney toxicity, threatening the physical and mental health of patients. Simultaneously, misuse of chemotherapeutic drugs can seriously endanger patients' lives. Therefore, to maintain the safety of chemotherapy for cancer patients and to reduce the incidence of adverse reactions to chemotherapy, many guidelines state that a comprehensive assessment of the cancer patient should be conducted and documented before chemotherapy. This recommended procedure, however, has yet to be extensively embraced in Chinese hospitals. As such, this study aimed to standardise the content of pre-chemotherapy assessment for cancer patients in hospitals and to improve nurses' adherence to pre-chemotherapy assessment of cancer patients by conducting a national multi-site evidence implementation in China, hence protecting the safety of cancer patients undergoing chemotherapy and reducing the incidence of adverse reactions to chemotherapy in patients.MethodsThe national multi-site evidence implementation project was launched by a JBI Centre of Excellence in China and conducted using the JBI approach to evidence implementation. A pre- and post-audit approach was used to evaluate the effectiveness of the project. This project had seven phases: training, planning, baseline audit, evidence implementation, two rounds of follow-up audits (3 and 9 months after evidence implementation, respectively) and sustainability assessment. A live online broadcast allowed all participating hospitals to come together to provide a summary and feedback on the implementation of the project.ResultsSeventy-four hospitals from 32 cities in China participated in the project, four withdrew during the project's implementation, and 70 hospitals completed the project. The pre-and post-audit showed a significant improvement in the compliance rate of nurses performing pre-chemotherapy assessments for cancer patients. Patient satisfaction and chemotherapy safety were also improved through the project's implementation, and the participating nurses' enthusiasm and belief in implementing evidence into practice was increased.ConclusionThe study demonstrated the feasibility of academic centres working with hospitals to promote the dissemination of evidence in clinical practice to accelerate knowledge translation. Further research is needed on the effectiveness of cross-regional and cross-organisational collaborations to facilitate evidence dissemination.

The efficacy and safety of leucine-enriched essential amino acids in knee osteoarthritis patients: A randomized controlled trial.

Supplementation with leucine-enriched essential amino acids (LEAAs) has shown efficacy in the recovery of muscle injury and activation of muscle synthesis. Muscle function in knee osteoarthritis is a crucial factor for managing pain and preserving ambulatory function. However, the efficacy and safety of LEAAs supplementation in patients with knee osteoarthritis have not been evaluated. In this prospective analysis, we evaluated the efficacy and safety of supplementation with 12 g of LEAAs daily for 8 weeks in knee-symptomatic osteoarthritis patients. For assessing the efficacy, clinical pain, calf circumference, and disability were assessed using questionnaires (visual analog scale, Knee Society Score, and 36-item short form survey [SF-36]), laboratory analyses (total protein and albumin), and radiologic study (dual-energy X-ray absorptiometry [DEXA]) for muscle and bone density. To evaluate safety, generalized or localized protein allergic reactions, complete blood count, liver and kidney function, and serum glucose were measured. Sixty-five participants, categorized into the experimental (n = 32) and control (n = 33) groups, were included in this 8-week trial from March 2022 to July 2022. A significantly higher efficacy was observed in the experimental group than in the control group, as indicated by muscle density in the DEXA scan (P = .001) and SF-36 (P < .001). The safety evaluation revealed no related generalized or local protein allergy. Hematological findings, serum glucose, and kidney and liver toxicity were not significantly different between the groups. Supplementation with leucine-enriched proteins is safe and efficacious in the improvement of muscle density and quality of life.

Co-assembly of cisplatin and dasatinib in hyaluronan nanogel to combat triple negative breast cancer with reduced side effects

Treatment for triple negative breast cancer (TNBC) remains a huge challenge due to the lack of targeted therapeutics and tumor heterogenicity. Cisplatin (Cis) have demonstrated favorable therapeutic response in TNBC and thus is used together with various kinase inhibitors to fight the heterogenicity of TNBC. The combination of Cis with SRC inhibitor dasatinib (DAS) has shown encouraging anti-TNBC efficacy although the additive toxicity was commonly observed. To overcome the severe side effects of this Cis involved therapy, here we co-encapsulated Cis and DAS into a self-assembled hyaluronan (HA) nanogel (designated as HA/Cis/DAS (HCD) nanogel) to afford the TNBC targeted delivery by using the 4T1 mouse model. The acquired HCD nanogel was around 181 nm in aqueous solution, demonstrating the pharmacological activities of both Cis and DAS. Taking advantages of HA's targeting capability towards CD44 that is overexpressed on many TNBC cells, the HCD could well maintain the anticancer efficacy of the Cis and DAS combination, significantly increase the maximum tolerated dose and relieve the renal toxicity in vivo. The current HCD nanogel provides a potent strategy to improve the therapeutic outcome of Cis and DAS combination and thus representing a new targeted treatment option for TNBC.

The nephroprotective effect of Quercetin in Cyclophosphamide-induced renal toxicity might be associated with MAPK/ERK and NF-κB signal modulation activity

The present study aimed to examine the protective effect of quercetin (QUE) on cyclophosphamide (CTX)-induced nephrotoxicity. For that purpose, 24 mice were divided into four groups (Control, QUE, CTX, and CTX + QUE). The CTX and CTX + QUE groups received 200 mg/kg of cyclophosphamide on the 1st and 7th days. The QUE and CTX + QUE groups were treated with 50 mg/kg of quercetin daily for 14 days. At the end of the experiment, the animals were sacrificed, and kidney samples were analyzed. The results indicated that CTX leads to severe morphological degenerations and disruption in renal function. Serum BUN, Creatinine, Uric acid, tissue Bax, Caspase 3, TNF-α and IL-1β expression levels were upregulated in the CTX group compared to Control and QUE groups (p < 0.05). Although MAPK/ERK phosphorylation level is not affected in CTX group, there was a significant increase in CTX + QUE group (p < 0.05), but the NF-κB was significantly suppressed in this group (p < 0.01). The RT-qPCR results showed that the cyt-c and the Bax/Bcl-2 ratio mRNA expression folds were upregulated in the CTX group (p < 0.01), which was downregulated in the CTX + QUE group. However, there was a significant difference in the CTX + QUE group compared to the Control and QUE groups (p < 0.01). The findings showed that administering quercetin along with cyclophosphamide alleviated renal injury by regulating apoptotic and inflammatory expression. Moreover, the administration of quercetin and cyclophosphamide could synergistically improve renal function test results, and activate cellular responses, which upmodulate MAPK/ERK phosphorylation and suppression of NF-κB.

Prenatal exposure to ethion caused maternal and foetal toxicity in rats

Ethion is a class II moderately toxic organothiophosphate pesticide. The main objective of this study was to evaluate the maternal and foetal toxicity of ethion in rats. Pregnant rats were divided into 5 groups. Group I served as control. Group II, III, IV, and V were orally administered with 0.86, 1.71, 3.43, and 6.9mg/kg of ethion respectively, from gestational day (GD) 6 to 19. Dams were sacrificed on GD 20. Maternal toxicity was assessed by body weight gain, foetal resorptions, oxidative stress, liver and kidney function tests, and histopathology. Foetal toxicity was assessed by physical status, gross, teratological and histopathological examination. Ethion caused dose-dependent reduction in maternal body weight gain, increased resorptions, and reduced gravid uterine weights. Elevated MDA levels and altered levels of GSH, SOD and catalase were recorded in pregnant dam serum and tissues. SGOT, SGPT, total bilirubin, urea, uric acid, and creatinine were elevated in ethion groups indicating liver and kidney toxicity. Histology of uterus revealed myometrial degeneration and mucosal gland atrophy in uterus of pregnant dams and degenerative changes in placenta. It showed histological alterations in liver,kidney, and lungs. There was reduction in the foetal body weights and placental weights, and degenerative changes in the foetal liver and kidney. Gross evaluation of foetuses showed subcutaneous hematoma. Skeletal evaluation showed partial ossification of skull bones, costal separation, and agenesis of tail vertebrae, sternebrae, metacarpals and metatarsals. The findings reveal that gestational exposure to ethion caused maternal and foetal toxicity in rats.

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.

Ameliorative impacts of astaxanthin against atrazine-induced renal toxicity through the modulation of ionic homeostasis and Nrf2 signaling pathways in mice.

Astaxanthin (ASX), a red pigment belonging to carotenoids, has antioxidant activity and anti-oxidative stress effect. Atrazine (ATZ), a frequently used herbicide, whose degradation products are the cause for nephrosis and other oxidative stress associated diseases. This study was aimed to reveal the potential protective mechanism of astaxanthin against atrazine-induced nephrosis. Atrazine was orally given (250mg/kg bw) to the mice along with astaxanthin (100mg/kg bw) for 28days. Serum biochemical indicators, oxidative stress biomarkers, ATPase activities, ion concentration, histomorphology, and various renal genes expression linked with apoptosis, Nrf2 signaling pathway, and aquaporins (AQPs) were assessed. It was found that serum creatinine (SCr), blood urea nitrogen (BUN), and MDA levels were significantly increased after the treatment of atrazine, whereas serum renal oxidative stress indicators like CAT, GSH, T-AOC, SOD decreased. Renal histopathology showed that atrazine significantly damaged renal tissues. The activities of Ca 2+-Mg 2+-ATPase were increased whereas Na +-K +-ATPase decreased significantly (P<0.05). Moreover, results confirmed that the expression of AQPs, Nrf2, and apoptosis genes were also altered after atrazine administration. Interestingly, astaxanthin supplementation significantly (P<0.05) improved atrazine-induced nephrotoxicity via decreasing SCr, BUN, oxidative stress, ionic homeostasis and reversing the changes in AQPs, Nrf2, and apoptosis gene expression. These findings collectively suggested that astaxanthin has strong potential ameliorative impact against atrazine induced nephrotoxicity.

Screening impacts of Tilmicosin-induced hepatic and renal toxicity in rats: protection by Rhodiola rosea extract through the involvement of oxidative stress, antioxidants, and inflammatory cytokines biomarkers.

Tilmicosin (TIL) is a semisynthetic macrolide antibiotic with a broad spectrum of activity derived from tylosin. TIL is effective in the treatment of bovine and ovine respiratory diseases caused by different microbes. In parallel, Rhodiola rosea (RHO) is a popular herbal remedy because of its anti-inflammatory and antioxidant qualities. The experiment lasted for 12days. Depending on the experimental group, the animals received either distilled water or RHO root extract dissolved in distilled water for 12days through a stomach tube, and the single subcutaneous injection on day 6 of the experiment of either 500 μL of 0.9% NaCl or TIL dissolved in 500 μL 0.9% NaCl. Samples and blood were collected for serum analysis, gene expression, and immunohistochemistry screening at liver and kidney levels. TIL injection increased serum levels of hepatic and renal markers (ALP, ALT, AST, TC, TG, creatinine, and urea) with decreased total proteins. In parallel, TIL induced hepatic and renal oxidative stress as there was an increase in malondialdehyde levels, with a decrease in catalase and reduced glutathione activities. Of interest, pre-administration of RHO inhibited TIL-induced increase in hepato-renal markers, decreased oxidative stress, and increased liver and kidney antioxidant activities. Quantitative RT-PCR showed that TIL increased the liver's HSP70 (heat shock protein), NFkB, and TNF-α mRNA expression. Moreover, TIL upregulated the expression of desmin, nestin, and vimentin expression in the kidney. The upregulated genes were decreased significantly in the protective group that received RHO. Serum inflammatory cytokines and genes of inflammatory markers were affected in liver tissues (HSP70, NFkB, and TNF-α) and kidney tissues (desmin, nestin, and vimentin)-TIL-induced hepatic vacuolation and congestion together with glomerular atrophy. The immunoreactivity of PCNA and HMGB1 was examined immunohistochemically. At cellular levels, PCNA was decreased while HMGB1 immunoreactivity was increased in TIL-injected rats, which was improved by pre-administration of RHO. RHO administration protected the altered changes in liver and renal histology. Current findings support the possible use of RHO to shield the liver and kidney from the negative effects of tilmicosin.

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

IntroductionZinc (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.MethodsHere, 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.ResultsThe 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).DiscussionThus, 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.

Genetic polymorphisms and clinical parameters associated with renal toxicity in Thai hematologic malignancy patients receiving high dose methotrexate

High-dose methotrexate (HD-MTX) is a widely used chemotherapy regimen for hematologic malignancies such as lymphomas and acute lymphoblastic leukemia, but its use can lead to adverse effects, including acute kidney injury (AKI), impaired liver function, and mucositis, causing extended hospital stays and delayed subsequent chemotherapy. Our study aimed to investigate the predictive factors for renal toxicities associated with HD-MTX in Thai patients undergoing treatment for hematologic malignancies. We enrolled 80 patients who underwent MTX-containing regimens, analyzing 132 chemotherapy cycles. The most common disease was primary central nervous system lymphoma (33%). Genetic polymorphisms were examined using the MassARRAY® system, identifying 42 polymorphisms in 25 genes. Serum creatinine and MTX levels were measured 24 and 48 h after MTX administration. For the primary outcome, we found that the allele A of MTRR rs1801394 was significantly related to renal toxicity (odds ratio 2.084 (1.001–4.301), p-value 0.047). Patients who exceeded the MTX threshold levels at 24 h after the dose had a significantly higher risk of renal toxicity (OR (95%CI) = 6.818 (2.350–19.782), p < 0.001). Multivariate logistic regression analysis with a generalized estimated equation revealed hypertension and age as independent predictors of increased MTX levels at 24 h after the given dose.

Targeted Thrombolysis with Magnetic Nanotherapeutics: A Translational Assessment

Plasminogen activators, such as recombinant tissue-type plasminogen activators (rtPAs), while effective in treating thromboembolic diseases, often induce hemorrhagic complications due to non-specific enzyme activities in the systemic circulation. This study evaluated the targeting efficiency, efficacy, biodistribution, and potential toxicity of a rtPA covalently attached to chitosan-coated magnetic nanoparticles (chitosan-MNP-rtPA). The thrombolytic activity of a chitosan-MNP-rtPA was preserved by protection from an endogenous plasminogen activator inhibitor-1 (PAI-1) in whole blood and after circulation in vivo, as examined by thromboelastometry. Single-photon emission computed tomography (SPECT) demonstrated real-time retention of a 99mTc-MNP-rtPA induced by magnet application in a rat embolic model; an 80% reduction in rtPA dosage for a chitosan-MNP-rtPA with magnetic guidance was shown to restore blood flow. After treatment, iron deposition was observed in the reticuloendothelial systems, with portal edema and neutrophil infiltration in the liver at a ten-fold higher dose but not the regular dose. Nevertheless, no liver or renal toxicity was observed at this higher dose. In conclusion, the liver may still be the major deposit site of rtPA nanocomposites after targeted delivery; chitosan-coated MNPs are potentially amenable to target therapeutics with parenteral administration.

An integrated view of cisplatin-induced nephrotoxicity, hepatotoxicity, and cardiotoxicity: characteristics, common molecular mechanisms, and current clinical management.

Cisplatin (CP) is a chemotherapy drug widely prescribed to treat various neoplasms. Although fundamental for the therapeutic action of the drug, its cytotoxic mechanisms trigger adverse effects in several tissues, such as the kidney, liver, and heart, which limit its clinical use. In this sense, studies point to an essential role of damage to nuclear and mitochondrial DNA associated with oxidative stress, inflammation, and apoptosis in the pathophysiology of tissue injuries. Due to the limitation of effective preventive and therapeutic measures against CP-induced toxicity, new strategies with potential cytoprotective effects have been studied. Therefore, this article is timely in reviewing the characteristics and main molecular mechanisms common to renal, hepatic, and cardiac toxicity previously described, in addition to addressing the main validated strategies for the current management of these adverse events in clinical practice. We also handle the main promising antioxidant substances recently presented in the literature to encourage the development of new research that consolidates their potential preventive and therapeutic effects against CP-induced cytotoxicity.

Preclinical safety evaluation of the ethanolic extract from campomanesia guazumifolia (cambess.) O. Berg fruits peels in rats

The toxicological potential of the ethanolic extract from Campomanesia guazumifolia (EECG), a species traditionally recognised for its antidiabetic, anti-inflammatory and hypercholesterolemic properties, was investigated in acute and subacute toxicity models in rats. In the acute toxicity test, 2000 mg/kg of EECG was administered orally in female rats, while male and female rats received 250, 500 or 750 mg/kg of EECG for the subacute toxicity test. No evidence of toxicity was observed in the animals acutely exposed, indicating that the LD50 is above 2000 mg/kg. However, repeated exposure to this extract resulted in alterations in important biochemical parameters indicative of hepatic and renal toxicity, including AST, ALT, creatinine, urea, and cholesterol. Additionally, some hematological parameters were also changed by the treatment. EECG demonstrated low toxicological potential. Nevertheless, given the observed changes in liver and kidney enzymes, further investigations into the protective effects of this extract following repeated administration are warranted.

Unraveling the Nephroprotective Potential of Papaverine against Cisplatin Toxicity through Mitigating Oxidative Stress and Inflammation: Insights from In Silico, In Vitro, and In Vivo Investigations.

Cisplatin is a potent compound in anti-tumor chemotherapy; however, its clinical utility is hampered by dose-limiting nephrotoxicity. This study investigated whether papaverine could mitigate cisplatin-induced kidney damage while preserving its chemotherapeutic efficacy. Integrative bioinformatics analysis predicted papaverine modulation of the mechanistic pathways related to cisplatin renal toxicity; notably, mitogen-activated protein kinase 1 (MAPK1) signaling. We validated protective effects in normal kidney cells without interfering with cisplatin cytotoxicity on a cancer cell line. Concurrent in vivo administration of papaverine alongside cisplatin in rats prevented elevations in nephrotoxicity markers, including serum creatinine, blood urea nitrogen, and renal oxidative stress markers (malondialdehyde, inducible nitric oxide synthase (iNOS), and pro-inflammatory cytokines), as tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and interleukin-6 (IL-6). Papaverine also reduced apoptosis markers such as Bcl2 and Bcl-2-associated X protein (Bax) and kidney injury molecule-1 (KIM-1), and histological damage. In addition, it upregulates antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) while boosting anti-inflammatory signaling interleukin-10 (IL-10). These effects were underlined by the ability of Papaverine to downregulate MAPK-1 expression. Overall, these findings show papaverine could protect against cisplatin kidney damage without reducing its cytotoxic activity. Further research would allow the transition of these results to clinical practice.

Discovery of digallic acid as XOD/URAT1 dual target inhibitor for the treatment of hyperuricemia

The development of XOD/URAT1 dual target inhibitors has emerged as a promising therapeutic strategy for the management of hyperuricemia. Here, through virtual screening, we have identified digallic acid as a novel dual target inhibitor of XOD/URAT1 and subsequently evaluated its pharmacological properties, pharmacokinetics, and toxicities. Digallic acid inhibited URAT1 with an IC50 of 5.34 ± 0.65 μM, which is less potent than benzbromarone (2.01 ± 0.36 μM) but more potent than lesinurad (10.36 ± 1.23 μM). Docking and mutation analysis indicated that residues S35, F241 and R477 of URAT1 confer a high affinity for digallic acid. Digallic acid inhibited XOD with an IC50 of 1.04 ± 0.23 μM. Its metabolic product, gallic acid, inhibited XOD with an IC50 of 0.91 ± 0.14 μM. Enzyme kinetic studies indicated that both digallic acid and gallic acid act as mixed-type XOD inhibitors. It shares the same binding mode as digallic acid, and residues E802, R880, F914, T1010, N768 and F1009 contribute to their high affinity. The anion group (carboxyl) of digallic acid contribute significantly to its inhibition activity on both XOD and URAT1 as indicated by docking analysis. Remarkably, at a dosage of 10 mg/kg in vivo, digallic acid exhibited a stronger urate-lowering and uricosuric effect compared to the positive drug benzbromarone and lesinurad. Pharmacokinetic study indicated that digallic acid can be hydrolyzed into gallic acid in vivo and has a t1/2 of 0.77 ± 0.10 h. Further toxicity evaluation indicated that digallic acid exhibited no obvious renal toxicity, as reflected by CCK-8, biochemical analysis (CR and BUN) and HE examination. The findings of our study can provide valuable insights for the development of XOD/URAT1 dual target inhibitors, and digallic acid deserves further investigation as a potential anti-hyperuricemic drug.

Toxicity study and ameliorative effects of the aqueous leaf extract of Lecanoidiscus cupanioides Planch (ex. Benth) on the stress-induced ulcer

Lecaniodiscus cupanioides Planch (ex. Benth) is effective in treating burns, fevers, and inflammatory conditions. This study investigates the toxicity effects of the aqueous leaf extract (ALE) of L. cupanioides and its effect on stress-induced ulcers in animal models. The plant was collected and a 1:30 (g/ml) plant powder/solvent ratio was extracted using an ultrasonic bath at 50 °C for 45 min. Up-and-down procedure was used for acute toxicity. During subacute toxicity testing, a total of 20 mice were divided into four groups of five animals each. While group 1 served as control, groups 2, 3, and 4 received 250, 500, and 1000 mg/kg of the extract daily for 21 days. On day 22nd, animals were sacrificed and samples were collected for hematology, biochemical, and histological analyses. In the stress-induced ulcer activity, male albino mice were randomly separated into 5 groups of 5 animals, treated with the test drug, and then dissected after being stressed using the water immersion model. LD50 was &gt; 5000 mg/kg, and in biochemical examination, there was a significant decrease in the ALP level at medium and high doses (p value &lt; 0.05) and non-significant alterations in the values of urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), body weight and hematology parameters (p &gt; 0.05). The histology results showed no evidence of liver and kidney toxicity. In conclusion, aqueous leaf extract of L. cupanioides was safe following a single dose (at 5000 mg/kg) and following repeated doses for 21 days (at 250, 500, and 1000 mg/kg). This study demonstrated that the extract had a significant effect on stress-induced ulcers at various dose levels when compared to the control (native, negative control, and omeprazole). The animals treated with 200mg/kg and 400mg/kg of the extract showed a significant increase in ulcer score, ulcer index, ulcer severity, and total acidity (p &lt; 0.05). The ulcer protection ability of the aqueous plant extract was dose-dependent.

Evaluation of Possible Ameliorative Role of Robinetin to Counteract Polystyrene Microplastics Instigated Renal Toxicity in Rats

Evaluation of Possible Ameliorative Role of Robinetin to Counteract Polystyrene Microplastics Instigated Renal Toxicity in Rats

Aloe-emodin: Progress in Pharmacological Activity, Safety, and Pharmaceutical Formulation Applications.

Aloe-emodin (AE) is an anthraquinone derivative and a biologically active component sourced from various plants, including Rheum palmatum L. and Aloe vera. Known chemically as 1,8-dihydroxy-3-hydroxymethyl-anthraquinone, AE has a rich history in traditional medicine and is esteemed for its accessibility, safety, affordability, and effectiveness. AE boasts multiple biochemical and pharmacological properties, such as strong antibacterial, antioxidant, and antitumor effects. Despite its array of benefits, AE's identity as an anthraquinone derivative raises concerns about its potential for liver and kidney toxicity. Nevertheless, AE is considered a promising drug candidate due to its significant bioactivities and cost efficiency. Recent research has highlighted that nanoformulated AE may enhance drug delivery, biocompatibility, and pharmacological benefits, offering a novel approach to drug design. This review delves into AE's pharmacological impacts, mechanisms, pharmacokinetics, and safety profile, incorporating insights from studies on its nanoformulations. The goal is to outline the burgeoning research in this area and to support the ongoing development and utilization of AE-based therapies.

Subchronic toxicity study of indium-tin oxide nanoparticles following an intratracheal administration into the lungs of rats

Abstract Objectives: We aimed to analyze the subchronic toxicity and tissue distribution of indium after the intratracheal administration of indium-tin oxide nanoparticles (ITO NPs) to the lungs of rats. Methods: Male Wistar rats were administered a single intratracheal dose of 10 or 20 mg In/kg body weight (BW) of ITO NPs. The control rats received only an intratracheal dose of distilled water. A subset of rats was periodically euthanized throughout the study from 1 to 20 weeks after administration. Indium concentrations in the serum, lungs, mediastinal lymph nodes, kidneys, liver, and spleen as well as pathological changes in the lungs and kidneys were determined. Additionally, the distribution of ionic indium and indium NPs in the kidneys was analyzed using laser ablation-inductively coupled plasma mass spectrometry. Results: Indium concentrations in the lungs of the two ITO NP groups gradually decreased over the 20-week observation period. Conversely, the indium concentrations in the mediastinal lymph nodes of the two ITO groups increased and were several hundred times higher than those in the kidneys, spleen, and liver. Pulmonary and renal toxicities were observed histopathologically in both the ITO groups. Both indium NPs and ionic indium were detected in the kidneys and their distributions were similar to the strong indium signals detected at the sites of inflammatory cell infiltration and tubular epithelial cells. Conclusions: Our results demonstrate that intratracheal administration of 10 or 20 mg In/kg body weight of ITO NPs in male rats produces pulmonary and renal toxicities.