Vitamin D and calcium co-therapy mitigates pre-established cadmium nephropathy by regulating renal calcium homeostatic molecules and improving anti-oxidative and anti-inflammatory activities in rat.

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 CdCl2 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-ß (TGF-ß1), 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 (CaV1.1/CaV3.1), 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/H2O2/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-ß1/iNOS/NGAL/KIM-1), oxidative stress (MDA/H2O2), and inflammation (TNF-α/IL-1ß/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 (CaV1.1/CaV3.1) 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.

Appraisal of the Antioxidant Activity, Polyphenolic Content, and Characterization of Selected Himalayan Herbs: Anti-Proliferative Potential in HepG2 Cells.

Natural antioxidants derived from plants have played a vital role in preventing a wide range of human chronic conditions and provide novel bioactive leads for investigators in pharmacotherapy discovery. This work was designed to examine the ethnopharmacological role of Urtica dioica (UD), Capsella bursa-pastoris (CBP), and Inula racemosa (IR). The total phenolic and flavonoid contents (TPC and TFC) were illustrated through colorimetric assays, while the antioxidant activity was investigated through DPPH and ABTS assays. The evaluation of phytochemicals by FT-IR of UD and CBP revealed high contents of aliphatic amines, while IR showed a major peak for ketones. The antioxidant activity, TPC and TFC were highest in the ethanol extract of UD, followed by CBP, and IR showed the lowest activity. All of the extracts revealed significant antioxidant capacities along a dosage gradient. Through a HPLC analysis at a wavelength of 280 nm, UD leaves demonstrated an intense peak of quercetin, and the peak for rutin was less intense. CBP (whole plant), instead, demonstrated a major yield of rutin, and a peak for quercetin was not observed in CBP. IR (rhizomes) showed both quercetin and rutin. All of the extracts were significantly cytotoxic to HepG2 cells after 48 h with the trend IR > UD > CBP. The outcomes of this study may be effective in the selection of specific plants as realistic sources of the bioactive components that might be useful in the nutraceutical progression and other biomedical efficacies.

Antibacterial Effects of Commiphora gileadensis Methanolic Extract on Wound Healing.

Commiphora gileadensis (CG) is a small tree distributed throughout the Middle East. It was traditionally used in perfumes in countries in this area. In Saudi Arabia, it was used to treat wounds burns and as an antidote to scorpion stings. This study aimed to evaluate the antimicrobial activity and cutaneous wound healing efficiency of the CG extracts using microbiological tests, rate of wound contraction and histopathological changes. CG plant were extracted using the methanol extraction technique; then, the methanolic extract was characterized using liquid chromatography coupled with mass spectrometry (LC−MS). Afterwards, a six-millimetre (mm) excision wound was induced in 60 male Balb/c mice. Mice were classified into two classes; each class consisted of three groups of 10 mice. In the non-infected wound class, the group I was assigned as control and received normal saline. Group II received gentamicin treatment, and group III treated with CG-methanolic extract. In the Staphylococcus aureus-infected class, group IV received normal saline, and groups V and VI were treated with gentamicin and CG-methanolic extract, respectively. The colonization of infected wounds was determined using colony-forming units (CFUs), and the percentage of wound contraction was measured in all groups. Finally, the histopathologic semi-quantitative determination of wound healing was evaluated by inflammatory cell infiltration, the presence of collagen fibres and granulation tissue, and the grade of re-epithelization. Composition analysis of the methanolic extract confirmed the presence of a high amount of ceramide (69%) and, to a lesser extent, hexosylceramide (18%) and phosphatidylethanolamine (7%) of the total amount. Additionally, there was a statistically significant difference between the percentage of wound contraction in the CG-treated and control groups in both Staphylococcus aureus-infected and non-infected wounds (p < 0.01). The colonization of the infected wounds was lower in the group treated with CG than in the control group (p < 0.01). In both non-infected and infected wounds, the CG-treated group showed significant statistical differences in inflammatory cell infiltration, collagen fibres, re-epithelization and granulation tissue formation compared with the control group (p < 0.01). The CG extract possesses antibacterial and anti-inflammatory properties that induce wound healing.

Copper-mediated ß-amyloid toxicity and its chelation therapy in Alzheimer's disease.

The link between bio-metals, Alzheimer's disease (AD), and its associated protein, amyloid-ß (Aß), is very complex and one of the most studied aspects currently. Alzheimer's disease, a progressive neurodegenerative disease, is proposed to occurs due to the misfolding and aggregation of Aß. Dyshomeostasis of metal ions and their interaction with Aß has largely been implicated in AD. Copper plays a crucial role in amyloid-ß toxicity, and AD development potentially occurs through direct interaction with the copper-binding motif of APP and different amino acid residues of Aß. Previous reports suggest that high levels of copper accumulation in the AD brain result in modulation of toxic Aß peptide levels, implicating the role of copper in the pathophysiology of AD. In this review, we explore the possible mode of copper ion interaction with Aß, which accelerates the kinetics of fibril formation and promote amyloid-ß mediated cell toxicity in Alzheimer's disease and the potential use of various copper chelators in the prevention of copper-mediated Aß toxicity. KEYWORDS: Short Twitter Statement: Authors explore copper ion interaction w/ Aß and kinetics of fibril formation in promoting amyloid-ß mediated cell toxicity in Alzheimer's disease and the potential use of copper chelators in the prevention of copper-mediated Aß toxicity. SHORT TWITTER STATEMENT: Authors explore copper ion interaction w/Aß and kinetics of fibril formation in promoting amyloid-ß mediated cell toxicity in Alzheimer's disease and the potential use of copper chelators in the prevention of copper-mediated Aß toxicity.