Toxicity mechanism of anthropogenic water contaminants: drinking water disinfection by-products (haloacetic acids) and particle associated contaminants from sealcoats (polyaromatic hydrocarbons) in lake sediments

Drinking water disinfection was one of the major public health accomplishments of 20th century. Water disinfection helps in reducing waterborne diseases like typhoid fever, cholera, and hepatitis A. However, chemical water disinfection also produces unwanted toxic chemicals, known as water disinfection by-products (DBPs). Most of the DBPs are cytotoxic, neurotoxic, genotoxic, mutagenic, carcinogenic and teratogenic but the toxicity mechanism is not completely understood. Therefore, the objectives of this dissertation were to i) understand the toxicity mechanisms and identify the molecular targets of all the regulated and non-regulated haloacetic acids (HAAs) water DBPs, ii) to differentiate among the toxicity mechanisms of mono-, di-, and triHAAs, iii) to evaluate the toxicity potential of chlorinated and chloraminated wastewater effluents, and iv) to evaluate the mutagenicity potential of the particle associated contaminants such as polyaromatic hydrocarbons (PAHs) associated with coal tar and soot, extracted from lake core sediments. Studies based on the toxicity mechanism of HAAs water DBPs demonstrated that monoHAAs were the strongest inhibitors of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) where, di-, and triHAAs were weaker inhibitors. MonoHAAs greatly reduced the ATP contents of the cells. Unlike monoHAAs, triHAAs increased the cellular ATP levels as compared to the negative controls. Exogenous pyruvate supplementation rescued cells from monoHAA-induced DNA damage and ATP depletion. These results confirmed that monoHAA-induced genotoxicity was due to GAPDH inhibition. HAAs not only affected the GAPDH kinetics and disturbed the cellular energy homeostasis but also increased pyruvate dehydrogenase complex (PDC) activity. Increased PDC activity by monoHAAs was due to changes in metabolite ratios e.g., ATP/ADP, and NADH/NAD ratio but the increase induced by di-, and triHAAs was due to the inhibition of pyruvate dehydrogenase kinase (PDK). Results demonstrated that HAA-induced toxicity is due to disruption in cellular energy homeostasis. This research demonstrated that there was a difference among the HAA-induced toxicity mechanisms and their molecular targets. MonoHAAs had an indirect effect on mitochondrial metabolism by inhibiting GAPDH, affecting the generation of pyruvate, inducing oxidative stress and reducing the final output of mitochondria in the form of ATP. Among monoHAAs, the rank order of toxicity was iodoacetic acid > bromoacetic acid >> chloroacetic acid (IAA > BAA >> CAA). This toxicity pattern was directly correlated with the inhibition of GAPDH kinetics, ATP depletion, and PDC activation. Whereas, di- and triHAAs induced toxicity by directly affecting mitochondrial metabolism by PDK inhibition, which led to PDC activation. The toxicity potential of chlorinated and chloraminated wastewater effluents extracted with XAD-8 and XAD-4 resins was evaluated. For chlorinated water, the organic extracts eluted from XAD-8 were more cytotoxic than that of the chloraminated wastewater extracts. However, the XAD-4 extracts of the chlorinated wastewaters and chloraminated wastewaters did not show any significance difference. Unlike the cytotoxicity analyses, the chloraminated wastewater XAD-8 extracts showed a higher genotoxic effect in mammalian cells than the XAD-4 extracts. Thus the major cytotoxicity and genotoxicity components in wastewater effluents were associated with hydrophobic acid fractions as compared to the transphilic acid fractions. The mutagenicity evaluation of the coal tar and soot associated polyaromatic hydrocarbons (PAHs) from lake sediments demonstrated that the coal tar and soot extracts were not direct acting mutagens but needed S9 microsomal activation. It was also found that coal tar extracts induced a higher rate of base pair substitution mutations as compared to the induction of frameshift mutations. Soot extracts induced a relatively higher rate of frameshift mutations as compared to the coal tar extract frameshift mutation rate

Toxicity assessment of Cedrus deodara oil compared to carbosulfan for Tenebrio molitor (Coleoptera: Tenebrionidae) adults

Specific compounds extracted from plants can control insect pests. The objective of this study was to evaluate the toxicity of deodar oil (phytopesticide) to adult mealworms Tenebrio molitor (Coleoptera: Tenebrionidae) compared with carbosulfan (synthetic insecticide), which exibits cholinesterase (ChE), glutamic pyruvic transaminase (GPT), and glutamic oxaloacetic transaminase (GOT) activities. The insecticides were applied through feeding, and the LC50 (lethal concentration) was calculated using the Finney method. The LC50 of deodar oil was higher than that of carbosulfan. The doses of both deodar oil and carbosulfan inhibited the ChE activity (p > 0.05) and enhanced the GPT and GOT activities (p < 0.05) in mealworm adults. Alterations in the activity of these biomarkers indicated that deodar oil could effectively control adult mealworms, being an environmentally low-impact method that can replace the use of chemical products

Haloacetic Acid Water Disinfection Byproducts Affect Pyruvate Dehydrogenase Activity and Disrupt Cellular Metabolism

The disinfection of drinking water has been a major public health achievement. However, haloacetic acids (HAAs), generated as byproducts of water disinfection, are cytotoxic, genotoxic, mutagenic, carcinogenic, and teratogenic. Previous studies of monoHAA-induced genotoxicity and cell stress demonstrated that the toxicity was due to inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), leading to disruption of cellular metabolism and energy homeostasis. DiHAAs and triHAAs are also produced during water disinfection, and whether they share mechanisms of action with monoHAAs is unknown. In this study, we evaluated the effects of mono-, di-, and tri-HAAs on cellular GAPDH enzyme kinetics, cellular ATP levels, and pyruvate dehydrogenase complex (PDC) activity. Here, treatments conducted in Chinese hamster ovary (CHO) cells revealed differences among mono-, di-, and triHAAs in their molecular targets. The monoHAAs, iodoacetic acid and bromoacetic acid, were the strongest inhibitors of GAPDH and greatly reduced cellular ATP levels. Chloroacetic acid, diHAAs, and triHAAs were weaker inhibitors of GAPDH and some increased the levels of cellular ATP. HAAs also affected PDC activity, with most HAAs activating PDC. The primary finding of this work is that mono- versus multi-HAAs address different molecular targets, and the results are generally consistent with a model in which monoHAAs activate the PDC through GAPDH inhibition-mediated disruption in cellular metabolites, including altering ATP-to-ADP and NADH-to-NAD ratios. The monoHAA-mediated reduction in cellular metabolites results in accelerated PDC activity by way of metabolite-ratio-dependent PDC regulation. DiHAAs and triHAAs are weaker inhibitors of GAPDH, but many also increase cellular ATP levels, and we suggest that they increase PDC activity by inhibiting pyruvate dehydrogenase kinase

Impact of seasonal variation on the growth dynamics of the marine catfish, Arius maculatus (Siluriformes: Ariidae) collected from Karachi fish harbour

Overfishing is the main cause of fish stock exploitation in the marine environment. In the current study growth dynamics of the marine catfish, Arius maculatus collected from Karachi Fish Harbour were studied. The relationship between total length and weight (W=aLb) was significantly linear (p3) in the monsoons season while in the pre- and post-monsoon the growth was reported as significantly negative allometric (b<3). The negative allometric growth shows that the fish are unable to maintain their shape in the specific season. It is suggested to stop the fishing activities for marine catfishes during the spawning and oral incubation period in pre-monsoon especially from February to mid-April to ensure sustainable fishing with a better growth dynamic.University of Karachi (Pakistan)Depto. de Biodiversidad, Ecología y EvoluciónFac. de Ciencias BiológicasTRUEpu