Mechanistic approach for the toxic effects of perfluorooctanoic acid on isolated rat liver and brain mitochondria

Background: Perfluorooctanoic acid (PFOA) is one of the most widely used perfluoroalkanes as surfactants, lubricants and processing aids in the production of polymers, which has also been detected in the environment, wildlife and human body. Animal studies indicated that PFOA caused a wide array of toxic effects including liver and brain dysfunction, carcinogenicity and reproductive and developmental toxicity. Based on the established role of mitochondria-mediated pathways in the observed toxic effects of many drugs and chemicals, in this study, the potential toxic effects of PFOA on mitochondria isolated from rat liver and brain have been investigated. Method: Mitochondria were isolated by differential centrifugation method and incubated with different concentrations of PFOA (0.5–1.5 mM). The effects of PFOA were assessed on a series of mitochondrial parameters including reactive oxygen species (ROS) formation, activities of mitochondrial complexes I/II/III, reduced glutathione (GSH) content, adenosine triphosphate (ATP) level, membrane potential, lipid peroxidation (LPO), mitochondrial swelling and cytochrome c release. Results: The data on liver mitochondria indicated that PFOA-induced ROS elevation in both mitochondrial complexes I and III, mitochondrial membrane potential collapse, swelling, cytochrome c release and decreased ATP level which induces apoptosis or necrosis. On brain mitochondria, PFOA showed fairly similar effects on the above-mentioned parameters. However, different results were obtained when the effect of PFOA was assessed on LPO and complex II activity. Conclusions: Due to the fact that PFOA had toxic effects on the mitochondria isolated, it could be suggested that mitochondrial toxicity could be a plausible mechanism for the toxic effects of this fluorochemical on liver and brain function

Carbon based nanomaterials for the detection of narrow therapeutic index pharmaceuticals

Precise detection of important pharmaceuticals with narrow therapeutic index (NTI) is very critical as there is a small window between their effective dose and the doses at which the adverse reactions are very likely to appear. Regarding the fact that various pharmacokinetics will be plausible while considering pharmacogenetic factors and also differences between generic and brand name drugs, accurate detection of NTI will be more important. Current routine analytical techniques suffer from many drawbacks while using novel biosensors can bring up many advantages including fast detection, accuracy, low cost with simple and repeatable measurements. Recently the well-known carbon Nano-allotropes including carbon nanotubes and graphenes have been widely used for development of different Nano-biosensors for a diverse list of analytes because of their great physiochemical features such as high tensile strength, ultra-light weight, unique electronic construction, high thermo-chemical stability, and an appropriate capacity for electron transfer. Because of these exceptional properties, scientists have developed an immense interest in these nanomaterials. In this case, there are important reports to show the effective Nano-carbon based biosensors in the detection of NTI drugs and the present review will critically summarize the available data in this field. © 2020 Elsevier B.V

Mechanistic approach for the toxic effects of perfluorooctanoic acid on isolated rat liver and brain mitochondria

Background: Perfluorooctanoic acid (PFOA) is one of the most widely used perfluoroalkanes as surfactants, lubricants and processing aids in the production of polymers, which has also been detected in the environment, wildlife and human body. Animal studies indicated that PFOA caused a wide array of toxic effects including liver and brain dysfunction, carcinogenicity and reproductive and developmental toxicity. Based on the established role of mitochondria-mediated pathways in the observed toxic effects of many drugs and chemicals, in this study, the potential toxic effects of PFOA on mitochondria isolated from rat liver and brain have been investigated. Method: Mitochondria were isolated by differential centrifugation method and incubated with different concentrations of PFOA (0.5–1.5 mM). The effects of PFOA were assessed on a series of mitochondrial parameters including reactive oxygen species (ROS) formation, activities of mitochondrial complexes I/II/III, reduced glutathione (GSH) content, adenosine triphosphate (ATP) level, membrane potential, lipid peroxidation (LPO), mitochondrial swelling and cytochrome c release. Results: The data on liver mitochondria indicated that PFOA-induced ROS elevation in both mitochondrial complexes I and III, mitochondrial membrane potential collapse, swelling, cytochrome c release and decreased ATP level which induces apoptosis or necrosis. On brain mitochondria, PFOA showed fairly similar effects on the above-mentioned parameters. However, different results were obtained when the effect of PFOA was assessed on LPO and complex II activity. Conclusions: Due to the fact that PFOA had toxic effects on the mitochondria isolated, it could be suggested that mitochondrial toxicity could be a plausible mechanism for the toxic effects of this fluorochemical on liver and brain function

Association between Blastocystis sp. infection and immunocompromised patients: a systematic review and meta-analysis

The significance of opportunistic infections in immunocompromised patients and the enigmatic pathogenicity of Blastocystis directed us to conduct the first global systematic review and meta-analysis on Blastocystis prevalence, odds ratios (ORs), and subtypes distribution in various immunocompromised patients (HIV/AIDS, cancer and hemodialysis patients, as well as transplant recipients). The systematic searching procedure was done in Web of Science, PubMed, Scopus, and Google Scholar databases for relevant published literature until November 11, 2020. Random-effects model was utilized to calculate the weighted estimates and 95 confidence intervals (95 CIs). The computed pooled prevalence of Blastocystis inferred from 118 papers (128 datasets) on immunocompromised patients was 10.3 (95 CI: 8.7-12.2), with 16.1 (95 CI: 11.3-22.2), 12.5 (95 CI: 8.5-18), 8.4 (95 CI: 6.6-10.6), and 6 (95 CI: 2.6-13.3) for hemodialysis patients, cancer patients, HIV/AIDS patients, and transplant recipients, respectively. Based on 50 case-control studies (54 datasets), the highest ORs were associated with cancer 2.81 (95% CI: 1.24-6.38, P = 0.013) and hemodialysis patients 2.78 (95% CI: 1.19-6.48, P = 0.018). The most frequent subtype being found in immunocompromised patients was ST3 41.7% (95% CI: 31.4-52.7%), followed by ST1 31.7% (95% CI: 23.2-41.8%) and ST2 23.1% (95% CI: 14.8-34.1%). Also, the weighted frequency of Blastocystis in various subgroups (publication year, WHO regions, geographical distribution, continents, and country income) was analyzed separately. In total, the results of the present meta-analysis highlighted that one's immunodeficiency status is probably associated with an increased Blastocystis infection, underpinning strict preventive measures to be taken

Resveratrol, curcumin and gallic acid attenuate glyoxal-induced damage to rat renal cells

Glyoxal (GO), a by-product of glucose auto-oxidation, is involved in the glycation of proteins/ lipids and formation of advanced glycation (AGE) and lipoxidation (ALE) end products. AGE/ALE were shown to contribute to diabetic complications development/progression such as nephropathy. Diabetic nephropathy progression has an oxidative nature. Given the antioxidant effects of polyphenols, potential protective effects of resveratrol, curcumin and gallic acid, in rat renal cells treated with GO, were evaluated in the present work. According to our results, incubation of GO with the cells reduced their viability and led to membrane lysis, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential collapse, and lysosomal membrane leakage. These findings were prevented by pre-treatment with resveratrol, curcumin and gallic acid. Mitochondrial and lysosomal toxic interactions appear to worsen oxidative stress/cytotoxicity produced by GO. Resveratrol, curcumin and gallic acid inhibited ROS formation and attenuated GO-induced renal cell death. © 2020 The Author(s

Dengue virus: a review on advances in detection and trends � from conventional methods to novel biosensors

Dengue virus is an important arbovirus infection which transmitted by the Aedes female mosquitoes. The attempt to control and early detection of this infection is a global public health issue at present. Because of the clinical importance of its detection, the main focus of this review is on all of the methods that can offer the new diagnosis strategies. The advantages and disadvantages of reported methods have been discussed comprehensively from different aspects like biomarkers type, sensitivity, accuracy, rate of detection, possibility of commercialization, availability, limit of detection, linear range, simplicity, mechanism of detection, and ability of usage for clinical applications. The optical, electrochemical, microfluidic, enzyme linked immunosorbent assay (ELISA), and smartphone-based biosensors are the main approaches which developed for detection of different biomarkers and serotypes of Dengue virus. Future efforts in miniaturization of these methods open the horizons for development of commercial biosensors for early-diagnosis of Dengue virus infection. Figure not available: see fulltext.. © 2019, Springer-Verlag GmbH Austria, part of Springer Nature

Anticancer and apoptosis-inducing effects of quercetin in vitro and in vivo

The present study focused on the elucidation of the putative anticancer potential of quercetin. The anticancer activity of quercetin at 10, 20, 40, 80 and 120 μM was assessed in vitro by MMT assay in 9 tumor cell lines (colon carcinoma CT-26 cells, prostate adenocarcinoma LNCaP cells, human prostate PC3 cells, pheocromocytoma PC12 cells, estrogen receptor-positive breast cancer MCF-7 cells, acute lymphoblastic leukemia MOLT-4 T-cells, human myeloma U266B1 cells, human lymphoid Raji cells and ovarian cancer CHO cells). Quercetin was found to induce the apoptosis of all the tested cancer cell lines at the utilized concentrations. Moreover, quercetin significantly induced the apoptosis of the CT-26, LNCaP, MOLT-4 and Raji cell lines, as compared to control group (P<0.001), as demonstrated by Annexin V/PI staining. In in vivo experiments, mice bearing MCF-7 and CT-26 tumors exhibited a significant reduction in tumor volume in the quercetin-treated group as compared to the control group (P<0.001). Taken together, quercetin, a naturally occurring compound, exhibits anticancer properties both in vivo and in vitro