Linagliptin ameliorates tacrolimus-induced renal injury: role of Nrf2/HO-1 and HIF-1α/CTGF/PAI-1.

BACKGROUND: Tacrolimus (TAC) is a frequently used immunosuppressive medication in organ transplantation. However, its nephrotoxic impact limits its long-term usage. This study aims to investigate the effect of linagliptin (Lina) on TAC-induced renal injury and its underlying mechanisms. METHODS AND RESULTS: Thirty-two Sprague Dawley rats were treated with TAC (1.5 mg/kg/day, subcutaneously) and/or Lina (5 mg/kg/day, orally) for 4 weeks. Histological examination was conducted, and serum and urinary biomarkers were measured to assess kidney function and integrity. Furthermore, ELISA, Western blot analysis and immunohistochemical assay were employed to determine signaling molecules of oxidative stress, profibrogenic, hypoxic, and apoptotic proteins. Tacrolimus caused renal dysfunction and histological deterioration evidenced by increased serum creatinine, blood urea nitrogen (BUN), urinary cystatin C, and decreased serum albumin as well as elevated tubular injury and interstitial fibrosis scores. Additionally, TAC significantly increased the expression of collagen type-1, alpha-smooth muscle actin (α-SMA), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor-beta1 (TGF-ß1) renal content. Moreover, TAC decreased the expression of nuclear factor erythroid-2-related factor2 (Nrf2), heme oxygenase 1 (HO-1), and mitochondrial superoxide dismutase (SOD2). In addition, TAC increased protein expression of hypoxia-inducible factor1-alpha (HIF-1α), connective tissue growth factor (CTGF), inducible nitric oxide synthase (iNOS), 8-hydroxy-2-deoxyguanosine (8-OHdG), as well as nitric oxide (NO), 4-hydroxynonenal, caspase-3 and Bax renal contents. Furthermore, TAC decreased Bcl-2 renal contents. The Lina administration markedly attenuated these alterations. CONCLUSION: Lina ameliorated TAC-induced kidney injury through modulation of oxidative stress, hypoxia, and apoptosis related proteins.

Hydroxytyrosol Alleviates Methotrexate-Induced Pulmonary Fibrosis in Rats: Involvement of TGF-ß1, Tissue Factor, and VEGF.

Methotrexate (MTX) is an indispensable drug used for the treatment of many autoimmune and cancerous diseases. However, its clinical use is associated with serious side effects, such as lung fibrosis. The main objective of this study is to test the hypothesis that hydroxytyrosol (HT) can mitigate MTX-induced lung fibrosis in rats while synergizing MTX anticancer effects. Pulmonary fibrosis was induced in the rats using MTX (14 mg/kg/week, per os (p.o.)). The rats were treated with or without HT (10, 20, and 40 mg/kg/d p.o.) or dexamethasone (DEX; 0.5 mg/kg/d, intraperitoneally (i.p.)) for two weeks concomitantly with MTX. Transforming growth factor beta 1 (TGF-ß1), interleukin-4 (IL-4), thromboxane A2 (TXA2), vascular endothelial growth factor (VEGF), 8-hydroxy-2-deoxy-guanosine (8-OHdG), tissue factor (TF) and fibrin were assessed using enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and RT-PCR. Pulmonary fibrosis was manifested by an excessive extracellular matrix (ECM) deposition and a marked increase in TGF-ß1 and IL-4 in lung tissues. Furthermore, cotreatment with HT or dexamethasone (DEX) significantly attenuated MTX-induced ECM deposition, TGF-ß1, and IL-4 expression. Similarly, HT or DEX notably reduced hydroxyproline contents, TXA2, fibrin, and TF expression in lung tissues. Moreover, using HT or DEX downregulated the gene expression of TF. A significant decrease in lung contents of VEGF, IL-8, and 8-OHdG was also observed in HT + MTX- or DEX + MTX -treated animals in a dose-dependent manner. Collectively, the results of our study suggest that HT might represent a potential protective agent against MTX-induced pulmonary fibrosis.

PRIMA-1 synergizes olaparib-induced cell death in p53 mutant triple negative human breast cancer cell line via restoring p53 function, arresting cell cycle, and inducing apoptosis.

This study concerned with assessing the effect of restoring p53 using PRIMA-1 on the anti-cancer activity of olaparib against TP53-mutant triple negative breast cancer (TNBC) cells and exploring the optimum synergistic concentrations and the underlying mechanism. Human BC cell lines, MDA-MB-231 with mutated TP53 gene, and MCF-7 with wild-type TP53 gene were treated with olaparib and/or PRIMA-1. The IC50 value for olaparib was significantly decreased by PRIMA-1 in MDA-MB-231 cells compared to MCF-7 cells. Contrary to MCF-7 cells, co-treatment with olaparib and PRIMA-1 had a synergistic anti-proliferative effect in MDA-MB-231 at all tested concentrations with the best synergistic combination at 45 and 8.5 µM, respectively, and furthermore PRIMA-1 enhanced olaparib-induced apoptosis. This synergistic apoptotic effect was associated with a significant boost in mRNA expression of TP53 gene, cell cycle arrest at G2/M phase, modulation of BRCA-1, BAX and Bcl2 proteins expressions, and induction of active caspase-3. These results present a clue for the utility of combined olaparib and PRIMA-1 in treatment of TP53-mutant TNBC invitro. PRIMA-1 triggers olaparib-induced MDA-MB-231 cell death in a synergistic manner via restoring TP53, decreasing BRCA-1 expression, cell cycle arrest, and enhancement of apoptosis via p53/BAX/Bcl2/caspase 3 pathway.

Estrogen Attenuates Diethylnitrosamine-Induced Hepatocellular Carcinoma in Female Rats via Modulation of Estrogen Receptor/FASN/CD36/IL-6 Axis.

This study was designed to evaluate the potential protective impact of estrogen and estrogen receptor against diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. The levels of liver injury serum biomarkers, liver content of interleukin-6 (IL-6), relative liver weight and distortion of liver histological pictures were significantly increased in ovariectomized (OVX) rats and SHAM rats that received DEN alone and were further exaggerated when DEN was combined with fulvestrant (F) compared to non-DEN treated rats. The OVX rats showed higher insults than SHAM rats. The tapering impact on these parameters was clear in OVX rats that received estradiol benzoate (EB), silymarin (S) or orlistat (ORS). The immunohistochemistry and/or Western blot analysis of liver tissues showed a prominent increase in fatty acid synthase (FASN) and cluster of differentiation 36 (CD36) expressions in OVX and SHAM rats who received DEN and/ or F compared to SHAM rats. In contrast to S, treatment of OVX rats with EB mitigated DEN-induced expression of FASN and CD36 in liver tissue, while ORS improved DEN-induced expression of FASN. In conclusion, the protective effect against HCC was mediated via estrogen receptor alpha (ER-α) which abrogates its downstream genes involved in lipid metabolism namely FASN and CD36 depriving the tumor from survival vital energy source. In addition, ORS induced similar mitigating effect against DEN-induced HCC which could be attributed to FASN inhibition and anti-inflammatory effect. Furthermore, S alleviated DEN-induced HCC, independent of its estrogenic effect.

Effect of Functional Groups on Low-Concentration Carbon Dioxide Capture in UiO-66-Type Metal-Organic Frameworks.

The selective capture of low-concentration CO2 from air or confined spaces remains a great challenge. In this study, various functional groups were introduced into UiO-66 to generate functionalized derivatives (UiO-66-R, R = NO2, NH2, OH, and CH3), aiming at significantly enhancing CO2 adsorption and separation efficiency. More significantly, UiO-66-NO2 and UiO-66-NH2 with high polarity exhibit exceptional CO2 affinity and optimal separation characteristics in mixed CO2/O2/N2 (1:21:78). In addition, the impressive stability of UiO-66-NO2 and UiO-66-NH2 endows them with excellent recycling stability. The effective adsorption and separation performances demonstrated by these two functional materials suggest their potential as promising physical adsorbents for capturing low-concentration CO2.

Zirconium Metal-Organic Cages: Synthesis and Applications.

ConspectusFor the last two decades, materials scientists have contributed to a growing library of porous crystalline materials. These synthetic materials are typically extended networks, including metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), or discrete materials like metal-organic cages (MOCs) and porous organic cages (POCs). Advanced porous materials have shown promise for various applications due to their modular nature and structural tunability. MOCs have recently garnered attention because of their molecularity that bestows them with many unique possibilities (e.g., solution-processability, structural diversity, and postsynthetic processability).MOCs are discrete molecular assemblies of organic ligands coordinated with either metal cations or metal oxide clusters of different nuclearities, resulting in architectures with inherent porosity. Notably, the molecular nature of MOCs endows them with easy solution-processability unattainable with traditional framework materials. To date, a number of stable MOCs have been reported, such as those based on Rh (Rh-O bond energy: 405 ± 42 kJ/mol), Fe (Fe-O bond energy: 407.0 ± 1.0 kJ/mol), Cr (Cr-O bond energy: 461 ± 8.7 kJ/mol), Ti (Ti-O bond energy: 666.5 ± 5.6 kJ/mol), and Zr (Zr-O bond energy: 766.1 ± 10.6 kJ/mol). Paddle-wheel MOCs have also shown great stability in aqueous environments due to their rigid backbones. The zirconium MOC (Zr-MOCs) family emerges as a class of very robust cages for which their high bond energy endows them with high hydrothermal stability.In 2013, we reported the first four zirconocene tetrahedrons assembled from trinuclear zirconium oxide clusters with ditopic or tritopic organic ligands. Since then, significant progress in the rational design of Zr-MOC has led to an assortment of structures dedicated to meaningful applications.In this Account, we highlight the recent progress in synthesizing Zr-MOCs and Zr-MOC-based higher dimensional frameworks and their applications dedicated in our laboratories and beyond. The general Zr-MOC synthetic strategy involves assembling Zr trinuclear clusters with organic ligands (rigid or flexible) containing various functional groups. This chemistry has afforded cages with structural versatility and active sites, e.g., amino groups, for postsynthetic modifications (PSMs). Since the extrinsic porosity of cage-based frameworks is relatively weak, the resulting frameworks are susceptible to structural rearrangement after solvent removal. To circumvent this limitation, increasing the hydrogen bond ratio and strength between interlinked cages and conducting in situ catalytic polymerizations have been reported to afford permanently porous structures amenable to host-guest reactions.To expand their potential applications, multifunctional Zr-MOCs are highly desired. Such multivariate MOCs can be attained by either employing the isoreticular expansion strategy to create MOCs with high surface areas or using mixed-ligand approaches to afford heterogeneous MOCs. In addition, amorphous MOCs, flexible organic ligands, new functionalities, and MOC-based extended networks are exciting new approaches to developing materials with structural versatility and enhanced characteristics. Thereby, we believe the stability and versatility of the Zr-MOC family hold great potential in expanding and addressing challenging applications.

Chiral proline-substituted porous organic cages in asymmetric organocatalysis.

The efficient preparation of chiral porous organic cages (POCs) with specific functions is challenging, and their application in asymmetric catalysis has not previously been explored. In this work, we have achieved the construction of chiral POCs based on a supramolecular tetraformyl-resorcin[4]arene scaffold with different chiral proline-modified diamine ligands and utilizing dynamic imine chemistry. The incorporation of V-shaped or linear chiral diamines affords the [4 + 8] square prism and [6 + 12] octahedral POCs respectively. The appended chiral proline moieties in such POCs make them highly active supramolecular nanoreactors for asymmetric aldol reactions, delivering up to 92% ee. The spatial distribution of chiral catalytic sites in these two types of POCs greatly affects their catalytic activities and enantioselectivities. This work not only lays a foundation for the asymmetric catalytic application of chiral POCs, but also contributes to our understanding of the catalytic function of biomimetic supramolecular systems.

Deacetylated cellulose acetate nanofibrous dressing loaded with chitosan/propolis nanoparticles for the effective treatment of burn wounds.

Every year, about 1 out of 9 get burnt in Egypt, with a mortality rate of 37%, and they suffer from physical disfigurement and trauma. For the treatment of second-degree burns, we aim at making a smart bandage provided with control of drug release (using chitosan nanoparticles) to enhance the healing process. This bandage is composed of natural materials; namely, cellulose acetate (CA), chitosan, and propolis (bee resin) as the loaded drug. Cellulose acetate nanofibers were deacetylated by NaOH after optimizing the reaction time and the concentration of NaOH solution, and the product was confirmed with FTIR analysis. Chitosan/propolis nanoparticles were prepared by ion gelation method with size ranging from 100 to 200 nm and a polydispersity index of 0.3. Chitosan/propolis nanoparticles were preloaded in the CA solution to ensure homogeneity. Loaded deacetylated cellulose nanofibers have shown the highest hydrophobicity measured by contact angle. Cytotoxicity of propolis and chitosan/propolis nanoparticles were tested and the experimental IC50 value was about 137.5 and 116.0 µg/mL, respectively, with p-value ≤0.001. In addition, chitosan/propolis nanoparticles loaded into cellulose nanofibers showed a cell viability of 89.46% in the cell viability test. In-vivo experiments showed that after 21 days of treatment with the loaded nanofibers repairing of epithelial cells, hair follicles and sebaceous glands in the skin of the burn wound were found in albino-mice model.

Solvatomorphism Influence of Porous Organic Cage on C2H2/CO2 Separation.

Porous organic molecular (POM) materials can exhibit solvatomorphs via altering their crystallographic packing in the solid state, but investigating real gas mixture separation by porous materials with such a behavior is still very rare. Herein, we report that a lantern-shaped calix[4]resorcinarene-based porous organic cage (POC, namely, CPOC-101) can exhibit eight distinct solid-state solvatomorphs via crystallization in different solvents. This POC solvatomorphism has a significant influence on their gas sorption capacities as well as separation abilities. Specifically, the apparent Brunauer-Emmett-Teller (BET) surface area determined by nitrogen gas sorption at 77 K for CPOC-101α crystallized from toluene/chloroform is up to 406 m2 g-1, which is much higher than the rest of CPOC-101 solvatomorphs with BET values less than 40 m2 g-1. More interestingly, C2H2 and CO2 adsorbed capacities, in addition to the C2H2/CO2 separation ability at room temperature for CPOC-101α, are superior to those of CPOC-101ß crystalized from nitrobenzene, the representative of POC solvatomorphs with low BET surface areas. These results indicate the possibility of adjusting gas sorption and separation properties of POC materials by controlling their solvatomorphs.

Association between interleukin 28B polymorphism and sustained virological response to sofosbuvir plus daclatasvir in chronic hepatitis C genotype 4 Egyptian patients.

WHAT IS KNOWN AND OBJECTIVE: Sofosbuvir has been approved as the first nonstructural protein 5B polymerase inhibitor with pan-genotypic activity against the hepatitis C (HCV) virus. Daclatasvir is a first-in-class hepatitis C virus nonstructural protein 5A replication complex inhibitor. We aimed to evaluate the usefulness of the reference single nucleotide polymorphism (rs12979860) interleukin 28B (CC genotype) for predicting sustained virological response to sofosbuvir plus daclatasvir in Egyptian patients infected with HCV-4. METHODS: Samples were collected at week zero. One hundred and thirty-one patients who reached the end of treatment (at week 12) were divided into three groups, according to their interleukin 28B genotype: Group A included 31 patients (CC genotype), group B included 79 patients (CT genotype) and group C had 21 patients (TT genotype). All patients received treatment for 3 months in the form of sofosbuvir plus daclatasvir with ribavirin (in case of cirrhotic patients) or without ribavirin (in case of non-cirrhotic patients). RESULTS AND DISCUSSION: Sustained virological response rate was significantly higher in patients with IL28B (CC genotype) vs. (non-CC genotype) (100 vs.88%) (p < 0.0001).These patients also showed lower rates of post-treatment relapse and non-response, compared with the CT and TT patients (0% vs. (7.59% and 28.5%, respectively) (p < 0.0001). Also, patients with CC genotype showed higher sustained virological response than non-CC genotypes on both cirrhotic (100% vs. 68.75%) and non-cirrhotic patients (100% vs. 91.66%) (p ≤ 0.0001). WHAT IS NEW AND CONCLUSION: Our results suggest that IL28B genotype contributes to the prediction of response to sofosbuvir plus daclatasvir.

A conceptual framework modeling of functional microbial communities in wastewater treatment electro-bioreactors.

Understanding the microbial ecology of a system allows linking members of the community and their metabolic functions to the performance of the wastewater bioreactor. This study provided a comprehensive conceptual framework for microbial communities in wastewater treatment electro-bioreactors (EBRs). The model was based on data acquired from monitoring the effect of altering different bioreactor operational parameters, such as current density and hydraulic retention time, on the microbial communities of an EBR and its nutrient removal efficiency. The model was also based on the 16S rRNA gene high-throughput sequencing data analysis and bioreactor efficiency data. The collective data clearly demonstrated that applying various electric currents affected the microbial community composition and stability and the reactor efficiency in terms of chemical oxygen demand, N and P removals. Moreover, a schematic that recommends operating conditions that are tailored to the type of wastewater that needs to be treated based on the functional microbial communities enriched at specific operating conditions was suggested. In this study, a conceptual model as a simplified representation of the behavior of microbial communities in EBRs was developed. The proposed conceptual model can be used to predict how biological treatment of wastewater in EBRs can be improved by varying several operating conditions.

Dynamic metal-organic frameworks for the separation of hydrogen isotopes.

Reversible structural transformation upon exposure to external stimuli can lead to breathing effect or gate-opening phenomena for dynamic metal-organic frameworks (MOFs), which endow them with excellent gas separation performance. The separation of hydrogen isotopes remains a huge challenge due to their nearly identical physical and chemical properties. The unique feature of dynamic MOFs, especially structural transition triggered by isotopes or by temperature, maximally enhances kinetic quantum sieving and contributes to the highly selective separation of hydrogen isotopes. Herein, we present some examples for the separation of hydrogen isotopes based on dynamic frameworks, and we expect to attract increasing attention to this research field.

The protective role of estrogen and its receptors in gentamicin-induced acute kidney injury in rats.

AIM: Investigating the impact of 17ß-Estradiol/estrogen receptors in gentamicin-induced nephrotoxicity. MAIN METHODS: Three weeks post-ovariectomy or sham surgery for the Wistar albino female rats, thirty sham rats were randomly grouped (n = 6), received either vehicle or gentamicin; the estrogen receptors down regulator (fulvestrant); gentamicin plus fulvestrant; gentamicin plus the phytoestrogen (genistein). Forty-eight ovariectomized rats were randomly grouped (n = 6), treated with either vehicle or gentamicin; fulvestrant; gentamicin plus fulvestrant; genistein; gentamicin plus genistein; estradiol benzoate; gentamicin plus estradiol benzoate. Just post-treatment termination, the traditional kidney injury biomarkers (serum creatinine and blood urea nitrogen) and novel biomarkers (serum Kidney injury molecule -1, cystatin C, lactate dehydrogenase and, gamma-glutamyl transferase) were determined. Bovine serum albumin labeled with fluorescence isothiocyanate assessed megalin expression/endocytic functionality in the proximal tubules epithelial cells (PTECs). The immunohistochemical investigation for the same-sectioned slides of PTECs assessed the correlation between estrogen receptors α and megalin receptors expression. Histopathological examination of PTECs and subjective scoring system graded the damage markers. KEY FINDINGS: Estrogen receptor α expression was markedly dimensioned post-ovariectomy, co-localized and inversely correlated to megalin expression. Serum levels of the novel biomarkers were directly proportional to megalin expression in the PTECs and inversely correlated with estrogen receptor α expression. The injury was exaggerated in ovariectomized and intact rats received fulvestrant. Supplementation with estrogen or genistein ameliorated this injury. SIGNIFICANCE: Estrogen/estrogen receptors have a protective impact on gentamicin-induced acute kidney injury. Estrogen receptors antagonist exacerbate the injury, and oppositely, estrogens or phytoestrogens improve it.

Analytical Study of Fuel Switching from Heavy Fuel Oil to Natural Gas in clay brick factories at Arab Abu Saed, Greater Cairo.

Arab Abu Saed area in Giza governorate, south to Cairo contains more than 228 clay brick kilns represent the largest cluster of brickworks in Egypt. Burning of Heavy Fuel Oil (HFO) in such kilns is the main source of air pollution in the surrounding locations. In this study, investigation of switching the fuel used in brick kilns from (HFO) to Natural Gas (NG) is carried out and the pollution loads are assessed in both cases. In addition, two Gaussian dispersion plume models are employed to estimate the concentration of primary pollutants; PM10, SO2, and NO2 at seven locations in the vicinity of Arab Abu Saed to determine the most adversely affected locations. Statistical analysis is applied to evaluate the correlation and conformity of the results of both models. Results show that using of NG leads to a significant reduction of pollution loads of PM10, SO2 and NO2 reaches 96%, 72%, and 24% respectively. In addition, the reduction of naturally occurring radionuclides in air is analyzed. Activity concentrations of Ra-226, Th-232 and K-40 in Bq/l for HFO were measured using HPGe detector for six HFO samples. Exposure due to air submersion of naturally occurring radionuclides in the study area leads to annual equivalent dose ranged between 2.16 mSv/y (received by Uterus) and 14 mSv/y (received by skin), and average effective dose 2.65 mSv/y which represent valuable exposure.

Ratiometric fluorescence detection of trace water in an organic solvent based on bimetallic lanthanide metal-organic frameworks.

Here we report a new sensor Tb97.11Eu2.89-L1 that enables ratiometric detection of trace water in CH3CN. As the water content increases from 0% to 2.5% (v/v%), Tb97.11Eu2.89-L1 exhibits an excellent linear relationship between the water content and I543/I615, as well as variable emissive light colors visible to the naked eye.

Nebivolol enhances the effect of alendronate against methylprednisolone-induced osteoporosis in rats.

This study aimed to assess the possible modulatory effect of nebivolol against methylprednisolone-induced osteoporosis in rats. Weekly administration of methylprednisolone (7 mg/kg), for six consecutive weeks caused significant increases in serum calcium, bone malondialdehyde, and hydroxyproline as well as serum alkaline phosphatase, but it significantly decreased serum phosphorous and osteocalcin, bone reduced glutathione, and nitric oxide (NO) as well as bone antioxidant enzymes activities compared with the control group. The results were confirmed by histopathological findings of femur bone. On the other hand, administration of alendronate (1 mg/kg) with nebivolol (1.5 mg/kg) orally and daily for seven consecutive days after methylprednisolone treatment caused marked mitigation in the above-mentioned parameters compared with methylprednisolone group. In conclusion, nebivolol proved to enhance the effect of alendronate in modulating methylprednisolone osteoporotic effect, which might be attributed to its release of NO together with its profound reducing capability in the oxidative cascade of bone tissue.

Protective effect of proanthocyanidins against doxorubicin-induced nephrotoxicity in rats.

Doxorubicin (DOX) exerts toxic effects in several organs particularly kidney. The present study aimed to assess the protective effect of proanthocyanidins (PAs) against DOX-induced nephrotoxicity in rats. A single dose of DOX (7.5 mg/kg, i.v.) significantly increased kidney weight, kidney/body weight ratio, serum urea, creatinine, tumor necrosis factor alpha levels, and kidney contents of malondialdehyde, nitric oxide, cyclooxygenase-2, and caspase-3 activity with significant reduction in final body weight, serum albumin, kidney contents of reduced glutathione (GSH), and superoxide dismutase activity as compared with control group. In contrast, pretreatment with PAs (200 mg/kg, p.o.) for 14 days before DOX and for 7 days after DOX ameliorated kidney function and oxidative stress parameters. Histopathological evidence confirmed the protective effects of PAs from the tissue damage induced by DOX. In conclusion, PAs have a multi-nephroprotective effect that might be attributed to its antioxidant, anti-inflammatory, and antiapoptoic activities.

Alpha lipoic acid prevents doxorubicin-induced nephrotoxicity by mitigation of oxidative stress, inflammation, and apoptosis in rats.

This study aimed to evaluate the protective effects of alpha lipoic acid (ALA) against doxorubicin (DOX)-induced nephrotoxicity in rats. A single dose of DOX (7.5 mg/kg i.v.) induced nephrotoxicity evidenced by significant elevations in kidney weight, kidney/body weight ratio, serum urea, creatinine, tumor necrosis factor alpha, and renal contents of malondialdehyde, nitric oxide, cyclooxygenase-2, and caspase-3. Also, it causes significant reduction in final body weight, serum albumin, renal contents of reduced glutathione and superoxide dismutase activity. Histopathological changes in the kidney tissue confirmed the nephrotoxic effect. In contrast, pretreatment with ALA (50 mg/kg, orally) for 14 days before DOX and for 7 days after DOX administration mitigated renal toxicity evidenced by greater improvement in the examined oxidative stress, inflammation, and apoptosis parameters. In conclusion, ALA had promising protective effects against DOX-induced nephrotoxicity that might be attributed to its antioxidant, anti-inflammatory, and antiapoptoic activities.

DNA Hybridization on Chitosan-Functionalized Silicon Substrate.

The ability of DNA to capture oligonucleotide molecules in solution is of great importance in genetics, medical diagnostics, and drug discovery. The DNA hybridization event in which the probe, which is usually a single-stranded DNA (ssDNA) covalently immobilized on a functionalized surface, recognizes the complementary target and forms a stable duplex structure that is the basis of highly specific bio recognizing devices. In this computational study, molecular modeling and Quantitative Structure Activity Relationship (QSAR) calculations were utilized at PM3 level in order to evaluate the interaction of aldehyde ssDNA on chitosan-functionalized silicon substrate and the biological activity of the proposed compounds. Molecular modeling of ssDNA 5'-(TTCA) attached on chitosan- functionalized silicon dioxide substrate was carried out. Molecular modeling and QSAR calculations were utilized at MM3 level in order to evaluate the interaction of target DNA on DNA probe on chitosan-functionalized silicon substrate through hydrogen bonding and the biological activity of the proposed compounds.

Thymol and Carvacrol Prevent Doxorubicin-Induced Cardiotoxicity by Abrogation of Oxidative Stress, Inflammation, and Apoptosis in Rats.

The aim of this study was to assess the possible protective effects of thymol and carvacrol (CAR) against doxorubicin (DOX)-induced cardiotoxicity. A single dose of DOX (10 mg/kg i.v.) injected to male rats revealed significant increases in serum lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme-MB, aspartate transaminase, tumor necrosis factor-alpha, and cardiac troponin levels. It also increased heart contents of malondialdehyde and caspase-3 accompanied by a significant reduction in heart content of reduced glutathione as well as catalase and superoxide dismutase activity as compared with the control group. In contrast, administration of thymol (20 mg/kg p.o.) and/or CAR (25 mg/kg p.o.) for 14 days before DOX administration and for 2 days after DOX injection ameliorated the heart function and oxidative stress parameters. Summarily, thymol was more cardioprotective than CAR. Moreover, a combination of thymol and CAR had a synergistic cardioprotective effect that might be attributed to antioxidant, anti-inflammatory, and antiapoptotic activities.