Current insecticide resistance status in Anopheles sacharovi and Anopheles superpictus populations in former malaria endemic areas of Turkey

Ulger, Celal/0000-0002-8051-3003; Simsek, Fatih/0000-0001-5962-0296WOS: 000465366900022PubMed: 30742803Anopheles sacharovi and Anopheles superpictus have a significant public health importance since they are primer and seconder malaria vectors of Turkey, respectively. As a result of intensive insecticide usage in historically malaria endemic regions of Turkey for long years, insecticide resistance problem has occurred inevitably. in this study, we aimed to investigate the involvement of the detoxification enzymes in insecticide resistance in Turkish An. sacharovi and An. superpictus populations in the Mediterranean and South-eastern Anatolia region where have a malaria history in the past. Bioassay results indicated that both An. sacharovi and An. superpictus populations are resistant to DDT, resistant or possible resistant to organophosphates and carbamates and finally mostly susceptible to pyrethroids. Although bioassays results indicated high DDT resistance in all mosquito populations, biochemical assays did not show significantly high GST levels in all strains. Almost all An. sacharovi and An. superpictus populations had an increased alpha and beta esterase activity levels while nearly half of the overall populations had an increased p-NPA esterase than the control group. Elevated levels of MFO frequency have been shown in the majority of the populations. Consequently, our results reveal that biochemical resistance mechanisms may play an important role in insecticide resistance in Turkish An. sacharovi and An. superpictus populations. These results give useful cues to monitor the insecticide resistance before it spreads throughout an entire population, enabling early intervention.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [112T479]This research was funded by the Scientific and Technological Research Council of Turkey (TUBITAK, Project No: 112T479)

Protective Effects of Valproic Acid, a Histone Deacetylase Inhibitor, against Hyperoxic Lung Injury in a Neonatal Rat Model

Histone acetylation and deacetylation may play a role in the pathogenesis of inflammatory lung diseases. We evaluated the preventive effect of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, on neonatal hyperoxic lung injury.Forty newborn rat pups were randomized in normoxia, normoxia+VPA, hyperoxia and hyperoxia+VPA groups. Pups in the normoxia and normoxia+VPA groups were kept in room air and received daily saline and VPA (30 mg/kg) injections, respectively, while those in hyperoxia and hyperoxia+VPA groups were exposed to 95% O2 and received daily saline and VPA (30 mg/kg) injections for 10 days, respectively. Growth, histopathological, biochemical and molecular biological indicators of lung injury, apoptosis, inflammation, fibrosis and histone acetylation were evaluated.VPA treatment during hyperoxia significantly improved weight gain, histopathologic grade, radial alveolar count and lamellar body membrane protein expression, while it decreased number of TUNEL(+) cells and active Caspase-3 expression. Expressions of TGFβ3 and phospho-SMAD2 proteins and levels of tissue proinflammatory cytokines as well as lipid peroxidation biomarkers were reduced, while anti-oxidative enzyme activities were enhanced by VPA treatment. VPA administration also reduced HDAC activity while increasing acetylated H3 and H4 protein expressions.The present study shows for the first time that VPA treatment ameliorates lung damage in a neonatal rat model of hyperoxic lung injury. The preventive effect of VPA involves HDAC inhibition

Histological examination of lung tissues by Haematoxylin-eosin (A-D, 100X magnification), Masson’s trichrome (E-H, 400X magnification), lamellar body membrane protein (LBMP) (I-L, 1000X magnification), and TUNEL-DAB stainings (M-P, 200X magnification) for Normoxia, Normoxia+VPA, Hyperoxia and Hyperoxia+VPA groups.

<p>Representative images show severe alveolar damage (panel C), cell infiltration and edema (panel G, arrow) in Hyperoxia group. Thickening of the alveolar septi or cell infiltration was not observed in Normoxia, Normoxia+VPA and Hyperoxia+VPA groups and panels A, B, D, E, F and H shows healthier and intact lung parenchymal appearance compared to hyperoxia group. Black arrows indicate positive immunoreactivity for LBMP and TUNEL(+) cells in panels I-P.</p

Bar graph depicting body weights of rat pups at birth and P10.

<p>*p<0.05 compared to Normoxia group; #p<0.05 compared to Normoxia+VPA group; and †p<0.05 compared to Hyperoxia group using One-Way ANOVA followed by post-hoc Tukey test.</p

Bar graphs depicting TGFβ1 (A), TGFβ3 (B) and phospho-SMAD2 (C) expressions in lung tissues of rat pups.

<p>Panel D depicts representative bands for each protein, including β-Actin, the protein which was used as a loading control for western blotting. *p<0.05 and **p<0.001 compared to Normoxia group; #p<0.05 and ##p<0.001 compared to Normoxia+VPA group; and †p<0.05 and ††p<0.001 compared to Hyperoxia group using One-Way ANOVA followed by post-hoc Tukey test.</p

Comparison of lung tissue pro-inflammatory cytokine levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and myeloperoxdase (MPO) activities and malonedialdehyde (MDA) content in all groups.

<p>*p<0,05 and</p><p><b>**</b>p<0,01 compared to Normoxia group; and</p><p>^†p<0,05 and</p><p>^‡p<0,01 compared to Hyperoxia group using One-Way ANOVA followed by post-hoc Tukey test.</p><p>Comparison of lung tissue pro-inflammatory cytokine levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and myeloperoxdase (MPO) activities and malonedialdehyde (MDA) content in all groups.</p

Bar graphs depicting histone deacetylase (HDAC) activity (A) as well as acetylated histone H3 (B) and acetylated histone H4 (C) protein expressions in lung tissues of rat pups.

<p>*p<0.05 and **p<0.001 compared to Normoxia group; #p<0.05 and ##p<0.001 compared to Normoxia+VPA group; and ††p<0.001 compared to Hyperoxia group using One-Way ANOVA followed by post-hoc Tukey test.</p