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Hazard Characterization and Dose–Response Assessment
Published in Ted W. Simon, Environmental Risk Assessment, 2019
The difference between toxicodynamics and toxicokinetics is evident in a very recent risk assessment of the organophosphate (OP) pesticide chlorpyrifos. The MOA for OPs is well known—inhibition of cholinesterases, with toxicity manifested as central and peripheral cholinergic effects.200 Thionophosphorus OPs such as chlorpyrifos do not directly inhibit acetyl cholinesterase (AChE), but must first be metabolized to the oxygen analog, or oxon, by CYP450 mixed-function oxidases, mainly occurring in the liver. Paraoxonase 1 (PON1) is an arylesterase that metabolizes organophosphate compounds. Chlorpyrifos oxon is inactivated by the enzyme paraoxonase (PON1) in the liver and other tissues,201,202 Genetic polymorphisms exist in the PON1 gene, and lifestyle factors such as the use of cholesterol-lowering medications and alcohol consumption may increase PON1 activity.203–206
Pesticide use in Thailand: Current situation, health risks, and gaps in research and policy
Published in Human and Ecological Risk Assessment: An International Journal, 2020
Wisanti Laohaudomchok, Noppanun Nankongnab, Somkiat Siriruttanapruk, Pakasinee Klaimala, Witoon Lianchamroon, Prokchol Ousap, Marut Jatiket, Puangrat Kajitvichyanukul, Noppadon Kitana, Wattasit Siriwong, Thiravat Hemachudhah, Jutamaad Satayavivad, Mark Robson, Lindsay Jaacks, Dana Boyd Barr, Pornpimol Kongtip, Susan Woskie
Although work on the neurodevelopmental effects of pesticides has been reported in the US and Europe, until recently little work had been done to look at the health consequences of pesticide exposures in children. The CWEND GEOHealth Hub has investigated the neurobehavioral impact of in-utero exposure to pesticides. Exposures to pesticides were measured in pregnant women and in the newborn meconium (Kongtip et al. 2013; 2017; Konthonbut et al. 2018; Onchoi et al. 2020). Higher maternal exposure to OP pesticides during pregnancy was associated with significantly increased Neonatal Behavioral Assessment Scale (NBAS) scores (Range of State and Habituation) and a borderline significant increase in the number of abnormal reflexes. These findings mirror those in the US (abnormal reflexes) and the Habituation score could represent a higher risk of behavioral issues associated with attention deficit hyperactivity disorder (ADHD) and autism (Kongtip et al. 2013; Woskie et al. 2017). At 5months of age, these babies were tested using the Bayley Scales of Infant Development and a significant decrease in infant cognitive and motor scores was found with increasing maternal OP pesticide levels during pregnancy (Kongtip et al. 2017). Other researchers in the network have reported that in Thai women with low paraoxonase (PON) enzyme activity, birth weight and length decreased as maternal OP metabolite levels increased. Also, maternal OP metabolite levels in the first trimester were associated with increased abnormal reflexes in newborns tested by NBAS, and second trimester OP pesticide levels were associated with decreases in motor and attention scores on NBAS (Naksen et al. 2015). Other Asian countries have conducted similar studies. For example, Bangladeshi women whose prenatal urinary 4-nitrophenol (metabolite of parathion and methyl parathion) levels were in the upper quartile were over 3 times more likely to deliver a preterm and small-for-gestational-age child. Similarly, women with measurable urinary levels of a diazinon metabolite were also at increased risk of having a child born with low birth weight (Jaacks et al. 2019).
Thymol Reduces Hepatorenal Oxidative Stress, Inflammation and Caspase-3#xd; Activation in Rats Exposed to Indomethacin
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Tijani Abiola Stephanie, Olori O. David, Ebenezer O. Farombi
Indomethacin administration has been reported to generate ROS that has been linked to lipid peroxidation with attendant disruption of cellular membranes resulting in leakage of resident enzymes and subsequent multi-organ toxicities [] through oxidative stress induction, inflammation and apoptosis [5]. Liver damage is usually assessed by ALT, AST, ALP, ALB, GGT, total BIL and LDH [38–40]. Elevated levels of serum ALT, AST, ALP, GGT and total BIL with low ALB level are sensitive markers of hepatic injury, cholestasis and hepatobiliary injury [41]. G6PDH protects the cellular redox potential in the course of oxidative stress [42]. Though these hepatic markers are used to assess liver overall damage, some of them are not specific to hepatic damage and are released into the blood stream after damage had occurred, thus, we evaluated more specific and early detected hepatic injury markers. GLDH, MDH SDH and PNP are enzymes whose serum activities are elevated during hepatocellular damage and are involved in the metabolic role of the liver [43–45] whereas PON1 is an ester hydrolase with both aryl esterase and paraoxonase activities and protects both LDL and HDL from oxidation [46]. ARG converts arginine to ornithine and urea. But, L-arginine metabolism is usually diverted to citrulline and nitrate during inflammation while hydroxyproline, a component of collagen whose presence in the serum could indicate the rates and progression of liver fibrogenesis [47]. In this study, elevated levels of ALT, AST, ALP, GGT, G6PDH, LDH, tBIL and dBIL GLDH, MDH, SDH, PNP, ARG, CIT, HYP with concomitant decrease in ALB and PON1 levels connotes hepatic toxicity that affects the integrity, metabolic, excretory, transport, synthetic and other liver functions. Our results conformed with previous reports [18,48]. The decreased levels of these biomarkers with the exception of ALB and PON1 that were increased following co-administration of IND with THY suggests that THY protects against IND-induced hepatic damage probably due to its ability to prevent hepatocytes membrane disruption and thus prevents leakage of hepatocytes constituents.
Chemoprotection by Kolaviron of Garcinia kola in Benzene-induced leukemogenesis in Wistar rats
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Olaniyi Solomon Ola, Esther Oladayo Ogunkanmbi, Emmanuel Babatife Opeodu
The induction of oxidative stress by benzene and its subsequent hematotoxicity had been reviewed [52]. The present work assesses the plasma redox status markers such as arylesterase activity, total sulfhydryl and advanced oxidation protein products of leukemic rats to investigate a link between onco-hematological diseases and oxidative stress. Prolonged oxidative stress has been associated with the occurrence of tumors [53]. The result showed a decrease in the plasma total thiol content with a concomitant increase in advanced oxidation protein products in leukemic rats relative to normal control. Advanced oxidation protein products (AOPPs) are oxidized protein products of oxidative stress, which resulted from chlorinated oxidants on plasma proteins [26,54], and its elevated level has been reported in some pathological conditions such as chronic kidney disease, diabetes, uremia and rheumatoid arthritis [55–57]. The thiol group present on protein especially over albumin constitutes the major in vivo antioxidant and reducing group in the body fluid [58]. Therefore, antioxidant status is indicated by the level of total thiol where the low protein thiol content correlates with an increase in peroxides and advanced oxidation protein products [58,59]. The increase in AOPP and low protein content in this study suggests the induction of oxidative stress due to benzene reactive metabolites that consequently led to oxidant-mediated protein damage [60]. However, supplementation of kolaviron in this study significantly alleviated the increased AOPP level and restored the total thiol status when compared to the leukemia control group. Moreover, in this study, there was a significant reduction in the plasma activity of arylesterase in the leukemic rats when compared to control. Arylesterase of paraoxonase 1 (PON 1) is an esterase enzyme that possesses lipophilic antioxidant characteristics [61]. The susceptibility and occurrence of some cancers like prostate, breast and hematologic cancers have been linked to PON1 polymorphism [62,63]. However, the reduction in arylesterase activity was mitigated on treatment with kolaviron when compared with the leukemia control group. Therefore, kolaviron may reduce the tendency of the development of the leukemia through enhanced activity of arylesterase of paraoxonase 1.