Volumen 10 (2017): Heft 4 (December 2017)

Parkinson’s disease (PD) is a highly prevalent neurodegenerative disorder, often associated with oxidative stress-induced transcriptional changes in dopaminergic neurons. Phenolic antioxidants, oleuropein (OLE) and rutin (RUT) have attracted a great interest due to their potential to counteract oxidative protein aggregation and toxicity. This study aimed at examining the effects of OLE and RUT against 6-OHDA-induced stress response in rat pheochromocytoma cells. When differentiated PC12 cells were exposed to oxidative stress composer 6-OHDA (100 μM, 8 h), a decreased mitochondrial membrane potential (ΔΨm) was observed along with a significant loss of cell viability and apoptotic nuclear changes. Exposure to 6-OHDA resulted in unfolded protein response (UPR) in differentiated PC12 cells as evidenced by an increased level of endoplasmic reticulum (ER)-localized transmembrane signal transducer IRE1α, adaptive response proteins ATF-4 and proapoptotic transcription factor CHOP. OLE or RUT pretreatment (24 h) at low doses (1-50 μM) protected the differentiated PC12 cells from 6-OHDA-induced cytotoxicity as assessed by increased viability, improved ΔΨm and inhibited apoptosis, whereas relatively high doses of OLE or RUT (>50 μM) inhibited cell growth and proliferation, indicating a typical hormetic effect. In hormetic doses, OLE and RUT up-regulated 6-OHDA-induced increase in IRE1α, ATF-4 and inhibited CHOP, PERK, BIP and PDI. 6-OHDA-activated XBP1 splicing was also inhibited by OLE or RUT. The presented results suggest that neuroprotection against 6-OHDA-induced oxidative toxicity may be attributable to neurohormetic effects of OLE or RUT at low doses through regulating mitochondrial functions, controlling persistent protein misfolding, activating and/or amplificating the adaptive response-related signaling pathways, leading to UPR prosurvival output.

Pesticides are one of the major sources of environmental toxicity and contamination. This study reports potential of lepidopteran insecticide formulation, named Flubendiamide, in altering compound eye architecture and bristle pattern orientation for four consecutive generations (P, F1, F2 and F3) in a non-target diptera, Drosophila melanogaster Meigen (Diptera: Drosophilidae). The concentrations of the insecticide formulation selected for treatment of Drosophila (50 and 100 μg/mL) were in accordance with practiced Indian field doses (50 μg/mL for rice and 100 μg/mL for cotton). This study showed trans-generational insecticide-induced changes in the morphology of the compound eyes of the non-target insect D. melanogaster.

The pentose phosphate pathway and glutathione-associated metabolism are the main antioxidant cellular defense systems. This study investigated the effects of the powerful antioxidant SMe1EC2 (2-ethoxycarbonyl-8-methoxy-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b] indolinium dichloride) on pentose phosphate pathway (PPP) and glutathione-dependent enzyme activities in aged diabetic and aged matched control rats. Diabetes was induced by streptozotocin injection in rats aged 13-15 months. Diabetic and control rats were divided into two subgroups, one untreated and one treated with SMe1EC2 (10 mg/kg/day, orally) for 4 months. SMe1EC2 ameliorated body weight loss, but not hyperglycemia of aged diabetic rats. Diabetes resulted in decreased glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD) and glutathione-S-transferase (GST), yet in unchanged glutathione reductase (GR) in the liver of aged diabetic rats. In the liver of the aged control rats, SMe1EC2 did not affect G6PDH, 6PGDH and GR, but it inhibited GST. SMe1EC2 also failed to affect diabetes-induced decline in 6PGDH, it ameliorated G6PDH but produced further decline in GST in the liver of aged diabetic rats. In the kidney of aged rats, G6PDH and GST were found to be comparable among the groups, but diabetes up-regulated 6PGDH and GR; these alterations were prevented by SMe1EC2. In the heart of aged diabetic rats, while GST remained unchanged, the recorded increase in G6PD, 6PGD, GR was prevented by SMe1EC2. Furthermore, an unchanged GR and remarkable increases in G6PD, 6PGD and GST were found in the lung of the aged diabetic group. These alterations were completely prevented by SMe1EC2. The results suggest that in aged rats SMe1EC2 can ameliorate the response of the kidney, heart and lung but not that of the liver against diabetes-induced glucotoxicity by interfering with the activity of redox network enzymes.

Alcohol and illicit drug abuse are major public health problems worldwide. Since alcohol is the predominant substance of choice in polydrug abusers, monitoring its use, along with urinary drug screening in patients in rehabilitation programs, appeared to be crucial in identifying patients at risk of alcohol disorders leading to impaired quality of life. Ethyl β-D-6-glucuronide, a non-oxidative, non-volatile, stable and minor direct ethanol metabolite, has a 6h to 4 day window of detection in urine after the last alcohol intake. Each of the 119 subjects (85 males, 34 females) registered with the Public Health Service for Drug Dependence Treatment provided a urine sample for ethylglucoronide (EtG) determination in an immunochemical test with a 500 ng/ml cutoff. All results were evaluated with confirmation criteria of a fully validated gas chromatography/mass spectrometry assay. The diagnostic performance of the EtG immunochemical test was assessed using Receiver Operating Characteristic Curve analysis. The immunochemical test specificity was 100% for EtG urinary values above 500 ng/ml. No false positive results were found. With levels below 500 ng/ml, 12% of the samples were classified as negative. The average consumption of the incorrectly classified subjects was 171 ng/ml, with a misclassification error of 6.5% to 18.5%. High agreement between EtG as determined in an immunochemical test and gas chromatography/mass spectrometry, suggests that the rapid EtG test is a reliable, cost-effective alcohol monitoring assay for patient management in many non-forensic settings, such as drug rehabilitation programs.

The leaves of Salacia lehmbachii are used ethnomedically across Africa for the treatment of different diseases its antimicrobial activity as well as toxicological profile were evaluated. Antimicrobial activity against clinical strains of Pseudomonas aeruginosa, Salmonella typhi, Staphylococus aureus, Shigella species, Eschericha coli and Proteus mirabilis were compared with Gentamycin. Toxicological investigation was determined by administering 100 mg/kg, 200 mg/kg and 400 mg/kg of the ethanol leaf extract to male Wistar rats for 21 days with distilled water as control. Hematological and biochemical parameters as well as the vital organs were examined. The ethanol extract inhibited the growth of P. aeruginosa, S. typhi, S. aureus, Shigella species, E. coli and P. mirabilis to varying extents. The LD₅₀ in rats was greater than 5000 mg/kg. Toxicological evaluation of the extract did not produce any significant effect on hematological and biochemical parameters and vital organs in rats. S. lehmbachii ethanol leaf extract did not demonstrate antimicrobial activity against selected microorganisms. Neither did it show any non-toxic effect on the parameters investigated in rats. Thus the extract can be considered safe when administered orally.

Despite modern approaches in molecular biology and genetics, we are still not able to identify the actual cause in more than 50% of all congenital defects. One-half of the unidentified cases is referred to as “multifactorial”. Detailed prenatal investigation of the fetus can discover the presence of congenital abnormality, which can worsen the process of postnatal adaptation. Retrospective analysis of newborns admitted to the Neonatal Department of Intensive Medicine (NDIM) in 2012-2016 with the aim to analyze how the process of postnatal adaptation can be changed by the presence of congenital abnormalities of lip and palate. During a five-year period, 13 newborns were admitted to NDIM (2 premature; 11 term newborns). Chromosomal abnormality was confirmed in one patient (Down syndrome) and in one patient suspicion of Patau syndrome was found. Twelve newborns had complete cheilognathopalatoschisis. Two premature newborns and two term newborns had perinatal asphyxia. In this group of patients, 33% had respiratory insufficiency without the presence of congenital heart abnormality, 66% had congenital heart abnormality with respiratory insufficiency, and 2 patients had feeding problems. Only one patient had a positive family history. The diagnosis of complete cheilognathopalatoschisis was confirmed prenatally only in 9 patients. We confirmed that clinical consequences of congenital abnormalities of lip and palate depend on the nature, localization and range of abnormalities, as well as on the genetic background and accompanying congenital abnormalities. Prenatal confirmation of the presence of congenital abnormalities has an important influence on the postnatal management of a patient.