Aluminum oxide nanoparticles (Al2O3 NPs) are among the most extensively utilized nanoparticles in nanotechnology and that have negative impacts on the environment. Therefore, the intention of this work is to investigate the protective and therapeutic effects of curcumin in nanoform (Cur NPs) against Al2O3 NPs induced kidney toxicity, oxidative stress, DNA damage, and changes in necrosis factor alpha (TNFα) and proliferating cell nuclear antigen (PCNA) expressions in male rats. Fifty healthy adult male were divided into five groups [G1, control; G2, received 50 mg/kg/day for 4 weeks of Cur NPs orally; G3, received 6 mg/kg BW orally for 4 weeks of Al2O3 NPs; G4, (Cur NPs + Al2O3 NPs) received Cur NPs and Al2O3 NPs at a dose similar to G2 and G3, respectively for 4 weeks; G5, (Al2O3 NPs + Cur NPs) received Al2O3 NPs at a dose similar to G3 for 4 weeks then received Cur NPs at a dose similar to G2 for another 4 weeks]. Current results revealed that Al2O3 NPs induced a significant elevation in serum urea, creatinine, chloride, calcium, kidney malondialdehyde (MDA), DNA damage, injury, TNFα and PCNA expressions and a significant depletion in serum potassium, kidney superoxide dismutase (SOD), glutathione (GSH) as compared to control. On the other hand, treatments of Al2O3 NPs with Cur NPs induced modulation in all altered parameters and improved kidney functions and structure, with best results for the Al2O3 NPs + Cur NPs than Cur NPs + Al2O3 NPs. In conclusion, Cur NPs has the capacity to mitigate the renal toxicity induced by Al2O3 NPs in male albino rats.

UNASSIGNED: This study explores the possible therapeutic role of rats and mice bone marrow-derived mesenchymal stem cells (BM-MSCs) on renal damage and toxicity brought on by carbon tetrachloride (CCl4) in Wistar rats.
UNASSIGNED: Following an intraperitoneal injection of CCl4 (0.5 mL/kg b.w. twice weekly) for eight weeks, male Wistar rats were intravenously treated with rats and mice BM-MSCs (1 × 106 cells in 0.2 mL Dulbecco\'s Modified Eagle Medium (DMEM)/rat/week) a week for four weeks. Kidney functions were evaluated and kidney samples were examined using hematoxylin and eosin (H&E), Masson\'s trichrome (MT) staining techniques, and electron microscopy analysis. Kidney cyclooxygenase-2 (COX-2), protein 53 (p53), and tumor necrosis factor-α (TNF-α) were detected by immunohistochemical staining techniques. Additionally, bioindicators of oxidative stress and antioxidant defense systems were identified in kidney tissue.
UNASSIGNED: In CCl4-injected rats, serum creatinine, urea, and uric acid levels significantly increased, as did renal lipid peroxidation (LPO), while superoxide dismutase, glutathione peroxidase (GPx), glutathione (GSH) transferase, and GSH levels significantly dropped in the kidneys. Histologically, the kidneys displayed a wide range of structural abnormalities, such as glomerular shrinkage, tubular dilations, inflammatory leukocytic infiltration, fibroblast proliferation, and elevated collagen content. Inflammatory cytokines like COX-2 and TNF-α as well as the pro-apoptotic mediator p53 were considerably upregulated. Treatment of BM-MSCs from mice and rats with CCl4-injected rats considerably reduced the previously noted abnormalities.
UNASSIGNED: By boosting antioxidant defense and reducing apoptosis and inflammation, BM-MSCs from mice and rats were able to enhance kidney function and histological integrity in rats that had received CCl4 injections.

UNASSIGNED: Cisplatin (Cis) is potent chemotherapy used to treating already many different types of cancer; however, it is found to correlate with nephrotoxicity and other adverse health consequences. Thymoquinone (TQ) is an antioxidant and anti-inflammatory molecule that may defend against the consequences of different chemotherapies. Thymoquinone uses, although, are negatively impacted by its weak solubility and inadequate biological availability.
UNASSIGNED: This investigation examined the efficacy of a new nanoparticle (NP) absorbing TQ in an Ehrlich Ascites Carcinoma (EAC) mice model to address its low solubility, enhance its bioavailability, and protect against Cis-induced nephrotoxicity.
UNASSIGNED: Following 4 treatment groups were included in this research: (1) control, (2) EAC, (3) EAC + Cis + Thymoquinone nanoparticle (TQ-NP) treated, and (4) EAC + Cis-treated.
UNASSIGNED: The study revealed that TQ-NP was efficacious in avoiding Cis-induced kidney problems in EAC mice, as well as restoring kidney function and pathology. Thymoquinone nanoparticle considerably reduced Cis-induced oxidative damage in renal tissue by augmenting antioxidant levels. According to tumor weight and histological investigation results, TQ-NP did not impair Cis\'s anticancer efficacy.
UNASSIGNED: Thymoquinone nanoparticle might be used as a potential drug along with Cis anticancer therapy to reduce nephrotoxicity and other side effects while maintaining Cis anticancer properties.
UNASSIGNED: Le cisplatine (CIS) est un puissant agent chimiothérapeutique utilisé pour le traitement de nombreux types de cancers. Le cisplatine est cependant corrélé à de la néphrotoxicité et à d’autres conséquences néfastes pour la santé. La thymoquinone (TQ) est une molécule antioxydante et anti-inflammatoire qui peut protéger contre les effets néfastes de différents agents chimiothérapeutiques. Les faibles solubilité et biodisponibilité de la TQ limitent toutefois son utilisation.
UNASSIGNED: Un modèle de souris atteintes d’un carcinome ascitique d’Ehrlich (souris EAC) a servi à vérifier l’efficacité d’une nouvelle nanoparticule (NP) absorbant la TQ pour remédier aux faibles solubilité et biodisponibilité de la TQ et protéger contre la néphrotoxicité induite par le CIS.
UNASSIGNED: Les quatre groupes suivants ont été examinés: i) témoin; ii) souris EAC; iii) souris EAC traitées par CIS + TQ-NP (thymoquinone-nanoparticule); iv) souris EAC traitées par CIS.
UNASSIGNED: L’étude a révélé que la TQ-NP était efficace pour éviter les problèmes rénaux induits par le CIS chez les souris EAC, de même que pour restaurer la fonction rénale et soigner la pathologie. En augmentant les niveaux d’antioxydants, la TQ-NP a considérablement réduit les dommages oxydatifs induits par le CIS dans le tissu rénal. Selon le poids des tumeurs et les résultats de l’étude histologique, la TQ-NP n’a pas altéré l’efficacité anticancéreuse du CIS.
UNASSIGNED: La TQ-NP pourrait potentiellement être utilisée avec le traitement anticancéreux par CIS afin de réduire la néphrotoxicité et les autres effets secondaires, sans altérer les propriétés anticancer du CIS.

[177Lu]Lu-PSMA-617 has recently been successfully approved by the FDA, the MHRA, Health Canada and the EMA as Pluvicto®. However, salivary gland (SG) and kidney toxicities account for its main dose-limiting side-effects, while its corresponding uptake and retention mechanisms still remain elusive. Recently, the presence of different ATP-binding cassette (ABC) transporters, such as human breast cancer resistance proteins (BCRP), multidrug resistance proteins (MDR1), multidrug-resistance-related proteins (MRP1, MRP4) and solute cassette (SLC) transporters, such as multidrug and toxin extrusion proteins (MATE1, MATE2-K), organic anion transporters (OAT1, OAT2v1, OAT3, OAT4) and peptide transporters (PEPT2), has been verified at different abundances in human SGs and kidneys. Therefore, our aim was to assess whether [177Lu]Lu-PSMA-617 and [225Ac]Ac-PSMA-617 are substrates of these ABC and SLC transporters. For in vitro studies, the novel isotopologue ([α,β-3H]Nal)Lu-PSMA-617 was used in cell lines or vesicles expressing the aforementioned human ABC and SLC transporters for inhibition and uptake studies, respectively. The corresponding probe substrates and reference inhibitors were used as controls. Our results indicate that [177Lu]Lu-PSMA-617 and [225Ac]Ac-PSMA-617 are neither inhibitors nor substrates of the examined transporters. Therefore, our results show that human ABC and SLC transporters play no central role in the uptake and retention of [177Lu]Lu-PSMA-617 and [225Ac]Ac-PSMA-617 in the SGs and kidneys nor in the observed toxicities.

Polystyrene microplastic (PS-MPs) contamination has become a worldwide hotspot of concern, and its entry into organisms can cause oxidative stress resulting in multi-organ damage. The plasticizer di (2-ethylhexyl) phthalate (DEHP) is a common endocrine disruptor, these two environmental toxins often occur together, but their combined toxicity to the kidney and its mechanism of toxicity are unknown. Therefore, in this study, we established PS-MPS and/or DEHP-exposed mouse models. The results showed that alone exposure to both PS-MPs and DEHP caused inflammatory cell infiltration, cell membrane rupture, and content spillage in kidney tissues. There were also down-regulation of antioxidant enzyme levels, increased ROS content, activated of the NF-κB pathway, stimulated the levels of heat shock proteins (HSPs), pyroptosis, and inflammatory associated factors. Notably, the co-exposure group showed greater toxicity to kidney tissues, the cellular assay further validated these results. The introduction of the antioxidant n-acetylcysteine (NAC) and the NLRP3 inhibitor (MCC950) could mitigate the changes in the above measures. In summary, co-exposure of PS-MPs and DEHP induced oxidative stress that activated the NF-κB/NLRP3 pathway and aggravated kidney pyroptosis and inflammation, as well as that HSPs are also involved in this pathologic injury process. This study not only enriched the nephrotoxicity of plasticizers and microplastics, but also provided new insights into the toxicity mechanisms of multicomponent co-pollution in environmental.

Heavy metals are found naturally in our environment and have many uses and applications in daily life. However, high concentrations of metals may be a result of pollution due to industrialization. In particular, cadmium (Cd), a white metal abundantly distributed in the terrestrial crust, is found in mines together with zinc, which accumulates after volcanic eruption or is found naturally in the sea and earth. High levels of Cd have been associated with disease. In the human body, Cd accumulates in two ways: via inhalation or consumption, mainly of plants or fish contaminated with high concentrations. Several international organizations have been working to establish the limit values of heavy metals in food, water, and the environment to avoid their toxic effects. Increased Cd levels may induce kidney, liver, or neurological diseases. Cd mainly accumulates in the kidney, causing renal disease in people exposed to moderate to high levels, which leads to the development of end-stage chronic kidney disease or death. The aim of this review is to provide an overview of Cd-induced nephrotoxicity, the mechanisms of Cd damage, and the current treatments used to reduce the toxic effects of Cd exposure.

The increasing use of the herbicide mixture of glyphosate, dicamba and 2-4-D to deal with glyphosate-resistant weeds raises concerns regarding human health and environmental risks. This study aimed to evaluate the effects of developmental exposure to glyphosate and a herbicide mixture containing glyphosate, dicamba and 2-4-D on rat dams\' kidney and thyroid function and offspring\'s health. Pregnant Wistar rats were exposed from day-6 of gestation till weaning to regulatory relevant doses of glyphosate corresponding to the European Union (EU) acceptable daily intake (ADI; 0.5 mg/kg bw/day), and the no-observed-adverse-effect level (NOAEL; 50 mg/kg bw/day), and to a mixture of glyphosate, dicamba and 2,4-D all at the EU ADI (0.5, 0.002 and 0.3 mg/kg bw/day) respectively. After weaning the dams were sacrificed and blood and organs were collected. The pups\' health was assessed by measuring viability, gestational and anogenital indices. Perinatal exposure to GLY alone and the herbicide mixture resulted in anti-androgenic effects in male offspring. In dams, exposure to glyphosate resulted in kidney glomerular and tubular dysfunction as well as increased thyroid hormone levels in a dose-dependent manner. Furthermore, exposure to the herbicide mixture resulted in effects similar to those observed with glyphosate at the NOAEL, suggesting at least an additive effect of the herbicide mixture at doses individually considered safe for humans.

The current pandemic has markedly shifted the focus of the global research and development ecosystem toward infectious agents such as SARS-CoV-2, the causative agent for COVID-19. A case in point is the chronic liver disease associated with hepatitis B virus (HBV) infection that continues to be a leading cause of severe liver disease and death globally. The burden of HBV infection is highest in the World Health Organization designated western Pacific and Africa regions. Tenofovir disoproxil fumarate (TDF) is a nucleoside analogue used in treatment of HBV infection but carries a potential for kidney toxicity. TDF is not metabolized by the cytochrome P450 enzymes and, therefore, its clearance in the proximal tubule of the renal nephron is controlled mostly by membrane transport proteins. Clinical pharmacogenomics of TDF with a focus on drug transporters, discussed in this perspective article, offers a timely example where resource-limited countries and regions of the world with high prevalence of HBV can strengthen the collective efforts to fight both COVID-19 and liver diseases impacting public health. We argue that precision/personalized medicine is invaluable to guide this line of research inquiry. In all, our experience in Ghana tells us that it is important not to forget the burden of chronic diseases while advancing research on infectious diseases such as COVID-19. For the long game with COVID-19, we need to address the public health burden of infectious agents and chronic diseases in tandem.

Cisplatin-based chemo-radiotherapy (CRT) is the standard treatment for advanced cervical cancer (CC) but the response rate is poor (46-72%) and cisplatin is nephrotoxic. Therefore, better treatment of CC is urgently needed. We have directly compared, for the first time, the cytotoxicity of four DDR inhibitors (rucaparib/PARPi, VE-821/ATRi, PF-477736/CHK1i and MK-1775/WEE1i) as single agents, and in combination with cisplatin and radiotherapy (RT) in a panel of CC cells. All inhibitors alone caused concentration-dependent cytotoxicity. Low ATM and DNA-PKcs levels were associated with greater VE-821 cytotoxicity. Cisplatin induced ATR, CHK1 and WEE1 activity in all of the cell lines. Cisplatin only activated PARP in S-phase cells, but RT activated PARP in the entire population. Rucaparib was the most potent radiosensitiser and VE-821 was the most potent chemosensitiser. VE-821, PF-47736 and MK-1775 attenuated cisplatin-induced S-phase arrest but tended to increase G2 phase accumulation. In mice, cisplatin-induced acute kidney injury was associated with oxidative stress and PARP activation and was prevented by rucaparib. Therefore, while all inhibitors investigated may increase the efficacy of CRT, the greatest clinical potential of rucaparib may be in limiting kidney damage, which is dose-limiting.

Cisplatin is an FDA approved anti-cancer drug that is widely used for the treatment of a variety of solid tumors. However, the severe adverse effects of cisplatin, particularly kidney toxicity, restrict its clinical and medication applications. The major mechanisms of cisplatin-induced renal toxicity involve oxidative stress, inflammation, and renal fibrosis, which are covered in this short review. In particular, we review the underlying mechanisms of cisplatin kidney injury in the context of NAD+-dependent redox enzymes including mitochondrial complex I, NAD kinase, CD38, sirtuins, poly-ADP ribosylase polymerase, and nicotinamide nucleotide transhydrogenase (NNT) and their potential contributing roles in the amelioration of cisplatin-induced kidney injury conferred by natural products derived from plants. We also cover general procedures used to create animal models of cisplatin-induced kidney injury involving mice and rats. We highlight the fact that more studies will be needed to dissect the role of each NAD+-dependent redox enzyme and its involvement in modulating cisplatin-induced kidney injury, in conjunction with intensive research in NAD+ redox biology and the protective effects of natural products against cisplatin-induced kidney injury.