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Hussain Almasmoum Laboratory Medicine Department, Faculty of Applied Medical Science, Umm Al-Qura University, Makkah, 7607, Saudi ArabiaCorrespondence: Hussain AlmasmoumLaboratory Medicine Department, Faculty of Applied Medical Science, Umm Al-Qura University, Al Abdeyah, Makkah, 7607, Saudi ArabiaTel +966 125270000-ext4521Email haamasmoum@uqu.edu.saAbstract: Colorectal cancer (CRC) is one of the most common types of cancers. It is associated with a poor prognosis and high mortality. The role of mucins (MUCs) in colon tumorigenesis is unclear, but it might be significant in the progression of malignancy. Some mucins, such as MUC1 and MUC13, act as oncogenes, whereas others, such as MUC2 and MUC6, are tumor suppressors. However, there are still mucins with unidentified roles in CRC. In this review, we discuss the reported roles of mucins in CRC. Moreover, we review the capability of the mucin family to serve as a sensitive and specific histopathological marker for the early diagnosis of CRC. Lastly, the role of mucin genes clustered on chromosome 7q22 in CRC and other cancers is also discussed.Keywords: colorectal cancer, mucins, MUC3, MUC12, MUC17, chromosome 7q22.1

Introduction: Blood donation is vital for healthcare; however, transfusion-transmitted infections (TTIs) pose a serious risk. This study investigated the seroprevalence of TTIs among Saudi blood donors., Methodology: This retrospective study included male blood donors aged ≥ 18 years who donated blood at Al-Noor Specialist Hospital in Makkah from January 2017 to December 2022. The blood units were screened for hepatitis B surface antigen (HBsAg) and core antibodies (HBc-IgG), hepatitis C antibodies (HCV-Abs), syphilis, HIV-1 antigen/antibody (HIV-1 Ag/Ab), human T-lymphotropic virus 1, 2 (HTLV-1/2), and malaria., Results: There were 40,287 donors with an average age of 44.33 ± 18.12 years, and 62.3% (n = 25103) were Saudis. The overall rate of TTIs seropositivity was 7.4% (n = 2953); HBc-IgG (6.1%; n = 2473) was the most common, followed by HCV-Abs (0.4%; n = 177), and syphilis (0.34%; n = 136). All cases were negative for malaria, whilst HIV and HTLV positive donors were 0.06% (n = 24) and 0.13% (n = 52), respectively. Syphilis was more prevalent among non-Saudis (0.24%; n = 83) than among Saudis (0.1%; n = 53), whereas anti-HBc antibodies seropositivity was significantly higher among Saudi (3.4%; n = 1373) than non-Saudi donors (2.7%; n = 1100)., Conclusions: Hepatitis B virus was the most frequently detected bloodborne pathogen, followed by hepatitis C virus and syphilis. Hepatitis B virus was also more prevalent among Saudi donors, whilst expatriates had higher rates of syphilis. Additional prospective multicenter studies are needed to accurately determine the prevalence of TTIs in Saudi Arabia., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Faisal Minshawi, Asim A Abdulshakoor, Emran M Alwakil, Ghaiyda T Basfar, Saeed Kabrah, Akhmed Aslam, Hibah Almasmoum, Abdulrahman Mujalli, Rabab H Moaminah, Ghadeer A Almoalad, Mohammed A Alwadani, Mohammad G Alzahrani, Kholoud A Alsehemi, Bassem Refaat.)

Background: Cadmium (Cd) is a major environmental pollutant and chronic toxicity could induce nephropathy by increasing renal oxidative stress and inflammation. Although vitamin D (VD) and calcium (Ca) prophylactic treatments attenuated Cd-induced cell injury, none of the prior studies measure their renoprotective effects against pre-established Cd-nephropathy., Aims: To measure the alleviating effects of VD and/or Ca single and dual therapies against pre-established nephrotoxicity induced by chronic Cd toxicity prior to treatment initiation., Methods: Forty male adult rats were allocated into: negative controls (NC), positive controls (PC), Ca, VD and VC groups. The study lasted for eight weeks and all animals, except the NC, received CdCl 2 in drinking water (44 mg/L) throughout the study. Ca (100 mg/kg) and/or VD (350 IU/kg) were given (five times/week) during the last four weeks to the designated groups. Subsequently, the expression of transforming growth factor-β (TGF-β1), inducible nitric oxide synthase (iNOS), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), VD synthesising (Cyp27b1) and catabolizing (Cyp24a1) enzymes with VD receptor (VDR) and binding protein (VDBP) was measured in renal tissues. Similarly, renal expression of Ca voltage-dependent channels (Ca V 1.1/Ca V 3.1), store-operated channels (RyR1/ITPR1), and binding proteins (CAM/CAMKIIA/S100A1/S100B) were measured. Serum markers of renal function alongside several markers of oxidative stress (MDA/H 2 O 2 /GSH/GPx/CAT) and inflammation (IL-6/TNF-α/IL-10) together with renal cell apoptosis and expression of caspase-3 were also measured., Results: The PC group exhibited hypovitaminosis D, hypocalcaemia, hypercalciuria, proteinuria, reduced creatinine clearance, and increased renal apoptosis/necrosis with higher caspase-3 expression. Markers of renal tissue damage (TGF-β1/iNOS/NGAL/KIM-1), oxidative stress (MDA/H 2 O 2 ), and inflammation (TNF-α/IL-1β/IL-6) increased, whilst the antioxidants (GSH/GPx/CAT) and IL-10 decreased, in the PC group. The PC renal tissues also showed abnormal expression of Cyp27b1, Cyp24a1, VDR, and VDBP, alongside Ca-membranous (Ca V 1.1/Ca V 3.1) and store-operated channels (RyR1/ITPR1) and cytosolic Ca-binding proteins (CAM/CAMKIIA/S100A1/S100B). Although VD was superior to Ca monotherapy, their combination revealed the best mitigation effects by attenuating serum and renal tissue Cd concentrations, inflammation and oxidative stress, alongside modulating the expression of VD/Ca-molecules., Conclusions: This study is the first to show improved alleviations against Cd-nephropathy by co-supplementing VD and Ca, possibly by better regulation of Ca-dependent anti-oxidative and anti-inflammatory actions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

This study investigated the chemotherapeutic effects of 5-fluorouracil (5-FU), metformin (Met), and/or thymoquinone (TQ) single/dual/triple therapies in the HT29, SW480 and SW620 colon cancer (CRC) cell lines. Cell cycle/apoptosis were measured by flow cytometry. The gene and protein expression of apoptosis (PCNA/survivin/BAX/Cytochrome-C/Caspase-3) and cell cycle (CCND1/CCND3/p21/p27) molecules, the PI3K/mTOR/HIF1α oncogenic pathway, and glycolysis regulatory enzymes were measured by quantitative-PCR and Western blot. Markers of oxidative stress were also measured by colorimetric assays. Although all treatments induced anti-cancer effects related to cell cycle arrest and apoptosis, the triple therapy showed the highest pro-apoptotic actions that coincided with the lowest expression of CCND1/CCND3/PCNA/survivin and the maximal increases in p21/p27/BAX/Cytochrome-C/Caspase-3 in all cell lines. The triple therapy also revealed the best suppression of the PI3K/mTOR/HIF1α pathway by increasing its endogenous inhibitors (PTEN/AMPKα) in all cell lines. Moreover, the lowest expression of lactate dehydrogenase and pyruvate dehydrogenase kinase-1 with the highest expression of pyruvate dehydrogenase were seen with the triple therapy, which also showed the highest increases in oxidative stress markers (ROS/RNS/MDA/protein carbonyl groups) alongside the lowest antioxidant levels (GSH/CAT) in all cell lines. In conclusion, this is the first study to reveal enhanced anti-cancer effects for metformin/thymoquinone in CRC that were superior to all monotherapies and the other dual therapies. However, the triple therapy approach showed the best tumoricidal actions related to cell cycle arrest and apoptosis in all cell lines, possibly by enhancing oxidative glycolysis and augmenting oxidative stress through stronger modulation of the PI3K/mTOR/HIF1α oncogenic network., (© 2023 International Union of Biochemistry and Molecular Biology.)

Background: Laboratory errors arise at any stage of testing. Detecting these inaccuracies before results are revealed might delay diagnosis and treatment, causing patient distress. Here, we studied the preanalytical errors in a hematology laboratory., Methods: This one-year retrospective analysis was conducted at the laboratory of a tertiary care hospital and included information on blood samples that were taken for hematology tests from both outpatients and inpatients. Laboratory records included sample collection and rejection information. The type and frequency of preanalytical errors were expressed as a proportion of total errors and sample number. Microsoft Excel was utilized to enter data. The results were presented in the form of frequency tables., Results: This research included 67,892 hematology samples. For preanalytical errors, 886 samples (1.3%) were discarded. The most common preanalytical error was insufficient sample (54.17%), and the least common was an empty/damaged tube (0.4%). Erroneous samples in the emergency department were mostly insufficient and clotted, whereas pediatric sample errors were caused by insufficient and diluted samples., Conclusion: Inadequate samples and clotted samples account for the vast majority of preanalytical factors. Insufficiency and dilutional errors were most frequent from pediatric patients. Adherence to best laboratory practices can drastically cut down on preanalytical errors.

Background: Chronic iron overload could induce nephropathy via oxidative stress and inflammation, and chelating therapy has limited efficacy in removing excess intracellular iron. Although vitamin D (VD) has shown potent antioxidant and anti-inflammatory effects, as well contribute to iron homeostasis, none of the previous studies measured its potential remedial effects against chronic iron toxicity., Aims: To measure the alleviating effects of deferasirox (DFX) and/or vitamin D (VD) single and combined therapies against nephrotoxicity induced by chronic iron overload., Methods: Forty male rats were divided into negative (NC) and positive (PC) controls, DFX, VD, and DFX/VD groups. The designated groups received iron for six weeks followed by DFX and/or VD for another six weeks. Then, the expression pattern of renal genes and proteins including hepcidin, ferroportin (FPN), megalin, transferrin receptor 1 (TfR1), ferritin heavy and light chains, VD receptor (VDR), VD synthesizing (Cyp27b1) and catabolizing (Cyp24a1) enzymes were measured alongside serum markers of renal function and iron biochemical parameters. Additionally, several markers of oxidative stress (MDA/H 2 O 2 /GSH/SOD1/CAT/GPx4) and inflammation (IL-1β/IL-6/TNF-α/IL-10) together with renal cell apoptosis and expression of caspase-3 (Casp-3) were measured., Results: The PC rats showed pathological iron and renal biochemical markers, hypovitaminosis D, increased renal tissue iron contents with increased Cyp24a1/Megalin/ferritin-chains/hepcidin, and decreased Cyp27b1/VDR/TfR1/FPN expression than the NC group. The PC renal tissues also showed abnormal histology, increased inflammatory (IL-1β/IL-6/TNF-α), oxidative stress (MDA/H 2 O 2 ), and apoptosis markers with decreased IL-10/GSH/SOD1/CAT/GPx4. Although DFX monotherapy reduced serum iron levels, it was comparable to the PC group in renal iron concentrations, VD and iron-homeostatic molecules, alongside markers of oxidative stress, inflammation, and apoptosis. On the other hand, VD monotherapy markedly modulated renal iron and VD-related molecules, reduced renal tissue iron concentrations, and preserved renal tissue relative to the PC and DFX groups. However, serum iron levels were equal in the VD and PC groups. In contrast, the best significant improvements in serum and renal iron levels, expression of renal iron-homeostatic molecules, oxidative stress, inflammation, and apoptosis were seen in the co-therapy group., Conclusions: iron-induced nephrotoxicity was associated with dysregulations in renal VD-system together with renal oxidative stress, inflammation, and apoptosis. While DFX reduced systemic iron, VD monotherapy showed better attenuation of renal iron concentrations and tissue damage. Nonetheless, the co-therapy approach exhibited the maximal remedial effects, possibly by enhanced modulation of renal iron-homeostatic molecules alongside reducing systemic iron levels., Availability of Data and Materials: All data generated or analysed during this study are included in this published article [and its Supplementary information files]., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Degradation of cytoplasmic mRNA in eukaryotes involves the shortening and removal of the mRNA poly(A) tail by poly(A)-selective ribonuclease (deadenylase) enzymes. In human cells, BTG2 can stimulate deadenylation of poly(A) bound by cytoplasmic poly(A)-binding protein PABPC1. This involves the concurrent binding by BTG2 of PABPC1 and the Caf1/CNOT7 nuclease subunit of the Ccr4-Not deadenylase complex. To understand in molecular detail how PABPC1 and BTG2 interact, we set out to identify amino acid residues of PABPC1 and BTG2 contributing to the interaction. To this end, we first used algorithms to predict PABPC1 interaction surfaces. Comparison of the predicted interaction surface with known residues involved in the binding to poly(A) resulted in the identification of a putative interaction surface for BTG2. Subsequently, we used pulldown assays to confirm the requirement of PABPC1 residues for the interaction with BTG2. Analysis of RNA-binding by PABPC1 variants indicated that PABPC1 residues required for interaction with BTG2 do not interfere with poly(A) binding. After further defining residues of BTG2 that are required for the interaction with PABPC1, we used information from published NMR chemical shift perturbation experiments to guide docking and generate a structural model of the BTG2-PABPC1 complex. A quaternary poly(A)-PABPC1-BTG2-Caf1/CNOT7 model showed that the 3' end of poly(A) RNA is directed towards the catalytic centre of Caf1/CNOT7, thereby providing a rationale for enhanced deadenylation by Caf1/CNOT7 in the presence of BTG2 and PABPC1., Competing Interests: Conflict of interest statement The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In the past decade, the use of marine mussels as seafood is being more popular. They considered being a rich source of various nutritional bioactive compounds that aroused the scientific community's interest. This study investigated the antioxidant and the antithrombotic consequences on Sprague-Dawley male rats after adding dried New Zealand mussel Perna canaliculus in their diet. The biochemical, hematological and histopathological changes were also observed. Forty rats were divided into four groups according to the amount of dried mussels in their diet, in addition to a control group that consumed a basal diet only. Group 1 consumed 25% dried mussels in its basal diet; Group 2 consumed 35% dried mussels in its basal diet, and Group 3 was consumed 45% dried mussels in its basal diet. The biochemical parameters showed improvements in liver function. Interestingly, the lipid profile decreased, especially the low-density lipoprotein cholesterol (LDL-C) levels which were reduced significantly in Group 3 (p < .01). These observations were accompanied by a decrease in iron levels significantly as the amount of dried mussels increased (p < .01). Furthermore, the noticed changes in the hematological profile prove that there is an increase in antithrombotic activity. Dried mussels had potent antioxidant effects in the liver as shown by increased lipid peroxide (p < .05), reduced glutathione (p < .05), and glutathione peroxidase (GSH-Px; p < .05). Additionally, antioxidant activity in the kidney was shown to increase through GSH-Px activity (p < .01). In conclusion, these results indicate that consuming dried mussels resulted in improved biochemical and antioxidants activities and could be used as an antithrombotic agent., (© 2021 Wiley Periodicals LLC.)

Although vitamin D (VD) and calcium (Ca) attenuate cadmium (Cd) metabolism, their combined antioxidant and anti-inflammatory actions against Cd toxicity have not been previously explored. Hence, this study measured the protective effects of VD ± Ca supplements against Cd hepatotoxicity. Forty adult male rats were distributed to: negative controls (NCs), positive controls (PCs), VD, Ca, and VD 3 and Ca (VDC) groups. All groups, except NC, received CdCl 2 in drinking water (44 mg/L) for 4 weeks individually or concurrently with intramuscular VD 3 (600 IU/kg; three times per week) and/or oral Ca (100 mg/kg; five times per week). The PC group showed abnormal hepatic biochemical parameters and increase in cellular cytochrome C, caspase-9, and caspase-3 alongside the apoptotic/necrotic cell numbers by terminal deoxynucleotidyl transferase dUTP nick end labeling technique. The PC hepatic tissue also had substantially elevated pro-oxidants (malondialdehyde [MDA]/H 2 O 2 /protein carbonyls) and inflammatory cytokines (interleukin 1β [IL-1β]/IL-6/IL17A/tumor necrosis factor-α), whereas the anti-inflammatory (IL-10/IL-22) and antioxidants (glutathione [GSH]/GPx/catalase enzyme [CAT]) markers declined. Hypovitaminosis D, low hepatic tissue Ca, aberrant hepatic expression of VD-metabolizing enzymes (Cyp2R1/Cyp27a1/cyp24a1), receptor and binding protein alongside Ca-membrane (Ca V 1.1/Ca V 3.1), and store-operated (RyR1/ITPR1) channels, and Ca-binding proteins (CAM/CAMKIIA/S100A1/S100B) were observed in the PC group. Both monotherapies decreased serum, but not tissue Cd levels, restored the targeted hepatic VD/Ca molecules' expression. However, these effects were more prominent in the VD group than the Ca group. The VDC group, contrariwise, disclosed the greatest alleviations on serum and tissue Cd, inflammatory and oxidative markers, the VD/Ca molecules and tissue integrity. In conclusion, this report is the first to reveal boosted protection for cosupplementing VD and Ca against Cd hepatotoxicity that could be due to enhanced antioxidative, anti-inflammatory, and modulation of the Ca pathways., (© 2020 Wiley Periodicals, Inc.)

Lead (Pb) is an extremely poisonous, non-essential trace element and toxicity develops in humans following frequent exposure to the heavy metal in polluted environmental and occupational settings. Pb induces hepatic damage through the depletion of the antioxidant system, enhancing cellular oxidative stress and stimulation of proinflammatory cytokines. Although the antioxidant and anti-inflammatory actions of vitamin D 3 (VD 3 ) are well-established, a minority of studies measured the protective actions of VD 3 against Pb toxicity. Therefore, this work studied the effects of vitamin VD 3 therapy on the fundamental molecular basis underlying hepatic injury induced by chronic Pb toxicity. Twenty-four adult male rats were distributed equally into the negative controls (NC), positive controls (PC) and VD3 groups. While both the PC and VD3 groups received Pb-acetate in drinking water (1000 mg/L) for four weeks, the latter group also received intramuscular VD3 injections (1000 IU/kg; 3 days/week) simultaneously with Pb. The liver enzymes together with the serum and hepatic tissue Pb concentrations increased markedly in the PC group compared with the NC group. Pb toxicity also drastically induced hepatocyte apoptosis/necrosis, increased the hepatic tissue concentrations of malondialdehyde and the pro-inflammatory cytokines (TGF-β, IL-4 & TNF-α) as well as reduced the anti-oxidative enzymes (GSH, GPx & CAT) and the anti-inflammatory cytokine, IL-10, compared with the NC group. Pb also significantly decreased the serum concentrations of VD3 and Ca 2+ . Additionally, the hepatic expressions of VD receptor, Cyp24a1 enzyme, L-type Ca 2+ -channel, calbindin-D 28k & -D 29k , calmodulin and calmodulin-dependent protein kinase II were significantly upregulated, whereas the VD binding protein, CYP2R1 enzyme and T-type Ca 2+ -channel were markedly inhibited at the gene and protein levels following Pb intoxication. VD3 alleviated the hepatic damage, inhibited the oxidative stress and pro-inflammatory molecules as well as upregulated the anti-oxidant and anti-inflammatory markers and restored the expression of the VD/Ca 2 + regulatory molecules compared with the PC group. VD3 supplementation discloses promising protective effects against Pb-induced hepatic damage, through its anti-inflammatory and antioxidant actions as well as by modulating the hepatocyte calcium homeostatic molecules., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Acute paracetamol (APAP) toxicity is a leading cause of liver, and less commonly renal, injuries through oxidative stress and inflammation. Albeit vitamin D (VD) is a well-known anti-oxidant and anti-inflammatory hormone, there is no report on its potential protective/therapeutic actions against APAP acute toxicity. This study, therefore, measured the interplay between APAP toxicity and the hepatorenal expressions of the VD-metabolising enzymes (Cyp2R1, Cyp27b1 & cyp24a1), receptor (VDR) and binding protein (VDBP) alongside the effects of VD treatment on APAP-induced hepatorenal injuries. Thirty-two male rats were distributed equally into negative (NC) and positive (PC) controls besides VD prophylactic (P-VD) and therapeutic (T-VD) groups. All groups, except the NC, received a single oral dose of APAP (1200 mg/kg). The P-VD also received by intraperitoneal injection two cycles of VD 3 (1000 IU/Kg/day; 5 days/week) prior to, and a third round after, APAP administration. Similarly, the T-VD group received VD 3 (3000 IU/Kg/day) for five successive days post-APAP intoxication. Euthanasia was on the sixth day post-APAP toxicity. The PC group had marked alterations in the hepatorenal biochemical parameters, upregulation in cellular cleaved caspase-3 as well as pronounced increase in the numbers of apoptotic/necrotic cells by TUNEL technique. The PC group plasma levels of 25-hydroxyvitamin D (25-OH VD) also declined markedly and coincided with significant inhibitions in the expression of Cyp2R1 and Cyp27b1 enzymes and VDR, whereas the VDBP and Cyp24a1 increased substantially, in the hepatorenal tissues at the gene and protein levels compared with the NC group. Coherently, the lipid peroxidation marker (MDA) and pro-inflammatory cytokines (IL1β, IL6, IL17A, IFN-γ & TNF-α) augmented significantly, while the anti-oxidative markers (GSH, GPx & CAT) and anti-inflammatory cytokines (IL10 & IL22) diminished substantially, in the PC hepatorenal tissues. Both VD regimens alleviated the APAP-induced hepatorenal damages and restored the 25-OH VD levels together with the hepatorenal expression of Cyp2R1, Cyp27b1, Cyp24a1, VDR and VDBP. Additionally, MDA and all the targeted pro-inflammatory cytokines declined, whereas all the anti-oxidative and anti-inflammatory markers increased, in both VD groups hepatorenal tissues and the results were significantly different than the PC group. Although the P-VD anti-inflammatory and anti-oxidative stress actions were more pronounced than the T-VD group, the results remained markedly abnormal than the NC group. In conclusion, this report is the first to reveal that the circulatory VD levels alongside the hepatorenal VD-metabolising enzymes and VDR are pathologically altered following acute APAP toxicity. Moreover, the prophylactic protocol showed better anti-oxidative and anti-inflammatory effects than the therapeutic regimen against APAP-induced hepatorenal injuries., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The Thymus vulgaris (T. vulgaris) has been used in foods for the flavor, aroma, and preservation and in folk medicines. The objective of the present work was to determine the antioxidant and protective effects of T. vulgaris extract against lead (Pb)-intoxicated rats. A thirty-two male Sprague-Dawley were randomly assigned into 4 equal groups and treated for six weeks as follows: group I (GP-I), served as negative control; GP-II, -III, and -IV received either Pb acetate in drinking water (500 mg/L), T. vulgaris extract (500 mg/kg/day) by oral gavage or Pb acetate with T. vulgaris extract, respectively. Blood samples were collected at the end of the study week 6 to measure the hepatic and renal biochemical markers, complete blood count alongside the serum levels of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis (TNF)-α, and interferon (IFN)-γ. Additionally, liver and kidney tissue specimens were collected for histopathology as well as to measure the antioxidant-reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) alongside the lipid peroxidation marker, malonaldehyde (MDA). The results indicated that Pb toxicity increased the serum levels of IL-1β, IL-6, and TNF-α, whereas IL-10 and IFN-γ were reduced. The results showed disturbed liver and renal functions; increased serum levels of ALT, AST, ALP, total bilirubin, creatinine, and urea; and decreased total protein, albumin, and calcium. The GSH, Gpx, and CAT levels were significantly decreased in the Pb-administrated group, while MDA was increased. However, regarding the hepatorenal markers, those animals treated with T. vulgaris alone did not induce any significant changes. Moreover, the combined treatment with T. vulgaris extract together with Pb showed significant improvement in Pb-induced toxicity in all the tested parameters compared to the negative control group. We investigated the potential protective effects of the medicinal plant T. vulgaris in vivo, since there are no publications that address the potential protective effect of this leaf extract against Pb-induced hepatorenal toxicity. Our studies concluded that the T. vulgaris extract reduces Pb overload in hepatorenal tissues, and that this has a potential immunomodulatory role, antioxidant activity, and a protective effect against Pb toxicity.

Background: Lead (Pb) is a toxic heavy metal and nephropathy is common with chronic exposure. Although vitamin D (VD) and calcium (Ca) showed promising protections, their co-administration was not previously investigated in Pb nephrotoxicity. This study measured the potential interactions and remedial effects of VD and/or Ca on established Pb nephropathy., Methods: Fifty adult male mice were equally distributed into: negative controls (NC), positive controls (PC), Ca, VD and VDC groups. The study duration was seven weeks and all groups, except the NC, received Pb acetate in drinking water (500 mg/L) throughout the study. The Ca, VD and VDC groups also received oral Ca (50 mg/kg; five times/week) and/or intramuscular VD (1000 IU/kg; three times/week) from week four till the end of the study., Results: The PC group showed substantial reduction in serum VD, hypocalcaemia, hypercalciuria and proteinuria alongside marked tissue inflammation, oxidative stress and apoptosis/necrosis. Pathological alterations were also detected in the mRNAs and proteins of the VD-metabolising enzymes, receptor and binding protein alongside several Ca-membrane channels, membrane transporters, intracellular binding proteins and mediators. While both monotherapies equally demonstrated moderate improvements, the VDC showed the utmost corrective actions on serum and tissue Pb concentrations, the inflammatory and antioxidative markers, the expressions of renal VD/Ca-molecules and tissue integrity. Moreover, the results were comparable between the VDC and NC groups., Conclusions: This report is the first to reveal potential enhanced remedial outcomes for combining VD and Ca against pre-existing Pb nephrotoxicity and the enhancements could be dependent on Ca-regulatory pathways., (Copyright © 2018 Elsevier B.V. All rights reserved.)