Altered Enzyme Activity Research Articles

Microplastics affect ecosystem multifunctionality: Increasing evidence from soil enzyme activities

AbstractMicroplastics (MPs) as emerging contaminants have a global occurrence, including both terrestrial and marine ecosystems. Soil enzymes contribute to maintaining ecosystem multifunctionality, for example, nutrient cycling, organic material decomposition, and carbon and climate regulation. Our present review highlights the impacts of MPs on soil enzyme activities, influencing factors, and the underlying mechanisms. Increasing findings confirm that MPs can change the activities of a range of soil enzymes involved in the biogeochemical cycling of C and N. However, current results are highly controversial. The effects of MPs highly vary from significant to nonsignificant and are dependent on polymer type, biodegradability, dosage, size, shape, and aging degree of MPs, and exposure conditions. Compared to traditional MPs, biodegradable MPs generally show more pronounced effects. MPs can change soil enzyme activities via different pathways. On one hand, MPs can directly change soil enzyme structure, leading to alterations in enzyme activity. On the other hand, MPs can create unique habitats, provide carbon sources for specific functional microbes producing enzymes, and release plastic additives and pollutants disturbing the production of these enzymes. Furthermore, MPs can alter soil physicochemical and biological properties, the availability of substrates, plants and soil fauna, regulating soil enzymes and their functions. In conclusion, MPs can regulate soil enzyme activities and pose a profound impact on ecosystem multifunctionality.

Tissue Inhibitor of Metalloproteinase 3 (TIMP3) mutations increase glycolytic activity and dysregulate glutamine metabolism in RPE cells

ObjectivesMutations in Tissue Inhibitor of Metalloproteinases 3 (TIMP3) cause Sorsby's Fundus Dystrophy (SFD), a dominantly inherited, rare form of macular degeneration that results in vision loss. TIMP3 is synthesized primarily by retinal pigment epithelial (RPE) cells, which constitute the outer blood-retinal barrier. One major function of RPE is the synthesis and transport of vital nutrients, such as glucose, to the retina. Recently, metabolic dysfunction in RPE cells has emerged as an important contributing factor in retinal degenerations. We set out to determine if RPE metabolic dysfunction was contributing to SFD pathogenesis. MethodsQuantitative proteomics was conducted on RPE of mice expressing the S179C variant of TIMP3, known to be causative of SFD in humans. Proteins found to be differentially expressed (P < 0.05) were analyzed using statistical overrepresentation analysis to determine enriched pathways, processes, and protein classes using g:profiler and PANTHER Gene Ontology. We examined the effects of mutant TIMP3 on RPE metabolism using human ARPE-19 cells expressing mutant S179C TIMP3 and patient-derived induced pluripotent stem cell-derived RPE (iRPE) carrying the S204C TIMP3 mutation. RPE metabolism was directly probed using isotopic tracing coupled with GC/MS analysis. Steady state [U–13C6] glucose isotopic tracing was preliminarily conducted on S179C ARPE-19 followed by [U–13C6] glucose and [U–13C5] glutamine isotopic tracing in SFD iRPE cells. ResultsQuantitative proteomics and enrichment analysis conducted on RPE of mice expressing mutant S179C TIMP3 identified differentially expressed proteins that were enriched for metabolism-related pathways and processes. Notably these results highlighted dysregulated glycolysis and glucose metabolism. Stable isotope tracing experiments with [U–13C6] glucose demonstrated enhanced glucose utilization and glycolytic activity in S179C TIMP3 APRE-19 cells. Similarly, [U–13C6] glucose tracing in SFD iRPE revealed increased glucose contribution to glycolysis and the TCA cycle. Additionally, [U–13C5] glutamine tracing found evidence of altered malic enzyme activity. ConclusionsThis study provides important information on the dysregulation of RPE glucose metabolism in SFD and implicates a potential commonality with other retinal degenerative diseases, emphasizing RPE cellular metabolism as a therapeutic target.

Linking soil nutrients, microbial community composition, and enzyme activities to saponin content of Paris polyphylla after addition of biochar and organic fertiliser

The application of organic fertilisers and biochar has become widespread in agroforestry ecosystems to enhance the yield and quality of crops and medicinal plants. However, their specific impact on both the yield and quality of Paris polyphylla (P. polyphylla), along with the underlying mechanisms, remains unclear. In this study, we investigated the distinct effects of organic fertiliser (at concentrations of 5% and 10%) and biochar application (at levels of 2% and 4%) on P. polyphylla saponin content. This content is intricately regulated by available soil nutrients, enzyme activities, and microbial community compositions and activities. Our results clearly demonstrated a significant increase in the saponin content, including total saponin, polyphyllin I (PPI), polyphyllin II (PPII), polyphyllin VI (PPVI), and polyphyllin VII (PPVII), in P. polyphylla following the application of both biochar and organic fertiliser. Moreover, in comparison to the control group, the addition of biochar and organic fertiliser led to a considerable rise in the activity of glycosyltransferase enzyme (GTS) and cycloartenol synthase (CAS) in P. polyphylla. Additionally, it increased soil available potassium (AK) and soil organic matter (SOM) concentration, along with the activity of urease, acid phosphatase, and catalase, although biochar amendment resulted in a decrease in nitrate nitrogen (NO3−-N) concentration. Crucially, our findings revealed a positive correlation between total saponin content and the activity of CAS in P. polyphylla, soil AK, SOM concentration, and the activities of urease, acid phosphatase, and catalase. Conversely, there was a negative correlation with NO3−-N content. Furthermore, the application of organic fertiliser and biochar significantly influenced microbial community structures and specific microbial taxa. Notably, total saponin content exhibited a positive relationship with the relative abundances of Dehalococcoidia, Saccharomycetes, and Agaricomycetes taxa while showing a negative correlation with the abundance of Verrucomicrobiae. In conclusion, the observed increase in saponin content can be attributed to the modulation of specific microbial taxa in soils, as well as alterations in soil nutrients and enzyme activities resulting from the application of biochar and organic fertiliser. This study identifies a potential mechanism for enhancing saponin content in the artificial cultivation of P. polyphylla.

Tenuazonic acid-induced mycotoxicosis in an immunosuppressed mouse model and its prophylaxis with cinnamaldehyde

Patients with impaired immune systems are particularly vulnerable to infections. With the increasing number of immunocompromised patients, it becomes necessary to design studies that evaluate the effects of toxic contaminants that are a part of our daily lives. Simultaneously, the management of these toxic components also becomes essential. Therefore, the present study evaluated the possible protective role of cinnamaldehyde (Cin) against tenuazonic acid-induced mycotoxicosis in the immunosuppressed murine model. Tenuazonic acid (TeA), a toxin usually produced by Alternaria species, is a common contaminant in tomato and tomato-based products. Evaluating the potential toxicity of a hazardous chemical necessitates the use of in vitro, in vivo, and in silico methods. Here, the immunomodulatory effect of TeA was assessed in vitro using mouse splenocytes. In silico docking was carried out for the tumour markers of eight organs and TeA. The haematological, histopathological, and biochemical aspects were analysed in vivo. The sub-chronic intoxication of mice with TeA showed elevated malondialdehyde, reduced catalase, and superoxide dismutase production, along with abnormal levels of aspartate aminotransferase and alanine transaminase. The treatment with Cin prevented TeA-induced alterations of antioxidant defense enzyme activities and significantly forbade TeA-induced organ damage, showing therapeutic effects and toxicity reduction in TeA-induced mycotoxicosis.

Norgestrel causes oxidative damage to the digestive gland of the clam Mactra veneriformis

Increasingly, progestins are being detected in aquatic environments, especially in aquaculture areas, and concern about their adverse effects on aquatic organisms is growing. However, the mechanisms underlying progestin-induced oxidative stress and the antioxidant response of aquatic invertebrates to progestin exposure are unknown. Researchers recently reported that norgestrel (NGT) likely causes oxidative stress in the clam Mactra veneriformis. In this study, we assessed reactive oxygen species (ROS) levels, antioxidant enzyme activity, malonaldehyde content, ultrastructure, and DNA damage in the digestive gland of M. veneriformis exposed to 7.69 or 756.62 ng/L of NGT for 21 days. We also conducted tandem mass tag-based quantitative proteomic analysis to detect the protein response and gain insights into response mechanisms in clams exposed to NGT. We found that NGT enhanced oxidative phosphorylation via the wingless/integrated signaling pathway and triggered ROS generation. The alterations of antioxidant enzyme activities suggested that these enzymes are involved in scavenging NGT-induced ROS. NGT weakened antioxidant defense by suppressing the antioxidant synthesis-related AMP-activated protein kinase/forkhead box O and sirtuin 1/forkhead box O pathways. Additionally, cell membrane dissolution, mitochondrial cristae rupture, DNA damage, elevation of malonaldehyde content, and oxidation of lipid, protein, and glucose occurred due to compromised redox homeostasis. Our results highlight the oxidative stress, antioxidant response, and oxidative damage induced by NGT in M. veneriformis and shed light on ecological risks of progestins to aquatic invertebrates.

Effects of Capnoperitoneum on Liver Functions: A Comparison Between Biliary and Non-Biliary Laparoscopic Surgeries.

Background: Laparoscopic procedures done using capnoperitoneum causes altered enzyme activity, which is subclinical most of time hence goes undiagnosed, leading to life threatening complications in patients with compromised hepatic function. Studies on altered hepatic enzyme activity has been done on patients undergoing laparoscopic cholecystectomy and seldom on laparoscopic non biliary surgeries, which we encounter daily. Hence aim of study was to compare effects of capnoperitoneum on liver functions in biliary and non-biliary surgeries.Methods: This prospective clinical observational study was conducted after obtaining institutional ethical clearance. Study was done on 60 patients undergoing surgeries. They were divided into two groups biliary and non-biliary based on undergoing surgeries. Patients blood sample was collected preoperatively and 24 hours postoperative for accessing liver enzymes. Statistical analysis done using SPSS version 23. Shapiro- wilk, paired ‘t’and chi- square tests were used to analyse the data. P &lt; 0.05 considered statistically significant.Results: The comparative parameters liver enzymes done pre and post operatively in biliary group total bilirubin, direct bilirubin, alkaline phosphatase, total protein, albumin and in non-biliary group aspartate transaminase, alkaline phosphatase, total protein, albumin were statistically significant.Conclusion: Post operative elevation in liver enzymes was found in both biliary and non biliary surgeries but enzymes specific to liver injury was found in biliary group.

Study of The Effect of Boswellia Leaf Extract on The Activity of Cardiac Enzymes (ALP, AST, ALT, LDH) Using Spectroscopic Methods

This study investigates the impact of Boswellia carterii leaf extracts on serum enzyme activity in myocardial infarction (MI) patients. Employing a comparative analysis between 60 healthy individuals and 40 cardiac patients, we measured the serum activity of ALP, AST, ALT, and LDH enzymes. Our findings reveal elevated enzyme activity in MI patients. We explored the inhibitory effects of aqueous, alcoholic, and ethyl acetate extracts of Boswellia carterii on these enzymes, demonstrating non-competitive inhibition. The inhibition ratio of ALT, ALP, and AST post-treatment was quantitatively assessed. Statistical analysis was conducted using SPSS-26 with independent t-tests. This research highlights the potential therapeutic role of Boswellia carterii in modulating enzyme activity associated with cardiac events, suggesting avenues for novel treatments in cardiac care.

Soil water content and RubisCO activity control the carbon storage in soil under different land uses in Sanjiang Plain, China

Soil carbon storage plays a crucial role in mitigating the climate warming and is significantly impacted by the land use pattern. To better understand soil carbon stability and the underlying microbial mechanism, based on qPCR, ELISA, and fluorescence techniques, the effects of land use changes on soil microbial abundance, enzyme activity, and soil carbon storage were investigated in the complex ecosystems of cropland, forestland, and wetland along three typical river (Wolvlan river, Bielahong river, Wusuli river) basin in Sanjiang Plain, China. We hypothesised that croplands soil carbon storage is lower than forestlands and wetlands, which is regulated by soil water content, microbe and enzyme activity. Results showed that topsoil TC in wetlands (85.54 mg·g−1) was higher than those in croplands (33.46 mg·g−1) and forestlands (46.13 mg·g−1). Topsoil water content increased 73.90 % and 71.64 % in wetlands than in farmland and forestlands, respectively. Additionally, reclamation diminished topsoil carbon storage. In croplands, soil dissolved organic carbon, microbial biomass carbon, microbial biomass nitrogen, available nitrogen, bacterial abundance, and soil enzymes (i.e., RubisCO, β-glucosidase, cellobiohydrolase, 1,4-N-acetylglucosaminidase and acid phosphatase) activities were substantially lower than those in wetlands. Structural equation modeling showed that soil carbon storage was positively related to soil water content and RubisCO activity but negatively related to soil bacterial abundance. Soil water content had the largest standardised total positive effect coefficient and indirectly influenced soil carbon storage by affecting RubisCO activity. Soil depth had a greater effect on SMC, hydrolase and site had a greater effect on bacteria and fungi abundance. The results highlight that the alteration of carbon fixing enzyme activity by soil water content is a crucial mechanism for soil carbon sequestration in response to land-use change. Management strategies that conserve natural wetlands, increase soil water content and minimize land disturbance would be effective in maintaining soil carbon stocks.

Aging-Related CYP3A Functional Changes in Chinese Older Patients: New Findings from Model-Based Assessment of Amlodipine.

Aging-related alterations in hepatic enzyme activity, particularly of the CYP3A, significantly impact drug efficacy and safety in older adults, making it essential to understand how aging affects CYP function for optimal drug therapy. The exogenous probe substrate method, a minimally invasive approach to assess liver metabolic enzyme activity in vivo, is effective in studying these changes. Amlodipine being extensively metabolized (> 90%) in the liver, primarily via cytochrome P450 enzyme CYP3A was selected as a probe to investigate and quantify the factors affecting the aging-related changes of CYP3A in the Chinese older population. Amlodipine concentration data were collected from an ongoing noninterventional clinical study conducted at Peking University Third Hospital. A physiologically-based pharmacokinetic modeling approach, grounded in population pharmacokinetic (PPK) analysis, was employed to physiologically quantify the aging-related changes in CYP3A function. A total of 132 amlodipine concentrations from 69 patients were obtained from the clinical study. PPK analysis shows that frailty phenotype but not age is a significant influence and frail patients have 37% greater plasma amlodipine exposure than nonfrail patients. This difference in CYP3A function may be attributed to a 63.2% lower CYP3A relative abundance in the frail patients, compared with that in the nonfrail patients. In the context of dose selection for older adults, focusing on frailty rather than chronological age should be recognized as a more relevant approach, because frailty might more accurately reflect the individual's biological age. Our study suggested a need to shift the research focus from chronological age to biological age.

Alterations in Soil Enzyme Activities in Response to New Generation Diamides

Alterations in Soil Enzyme Activities in Response to New Generation Diamides

Long-Term High-Fat Diet Limits the Protective Effect of Spontaneous Physical Activity on Mammary Carcinogenesis.

Breast cancer is influenced by factors such as diet, a sedentary lifestyle, obesity, and postmenopausal status, which are all linked to prolonged hormonal and inflammatory exposure. Physical activity offers protection against breast cancer by modulating hormones, immune responses, and oxidative defenses. This study aimed to assess how a prolonged high-fat diet (HFD) affects the effectiveness of physical activity in preventing and managing mammary tumorigenesis. Ovariectomised C57BL/6 mice were provided with an enriched environment to induce spontaneous physical activity while being fed HFD. After 44 days (short-term, ST HFD) or 88 days (long-term, LT HFD), syngenic EO771 cells were implanted into mammary glands, and tumour growth was monitored until sacrifice. Despite similar physical activity and food intake, the LT HFD group exhibited higher visceral adipose tissue mass and reduced skeletal muscle mass. In the tumour microenvironment, the LT HFD group showed decreased NK cells and TCD8+ cells, with a trend toward increased T regulatory cells, leading to a collapse of the T8/Treg ratio. Additionally, the LT HFD group displayed decreased tumour triglyceride content and altered enzyme activities indicative of oxidative stress. Prolonged exposure to HFD was associated with tumour growth despite elevated physical activity, promoting a tolerogenic tumour microenvironment. Future studies should explore inter-organ exchanges between tumour and tissues.

Exploring current and emerging therapies for porphyrias.

Porphyrias are rare, mostly inherited disorders resulting from altered activity of specific enzymes in the haem synthesis pathway that lead to accumulation of pathway intermediates. Photocutaneous symptoms occur when excess amounts of photoreactive porphyrins circulate in the blood to the skin, whereas increases in potentially neurotoxic porphyrin precursors are associated with neurovisceral symptoms. Current therapies are suboptimal and their mechanisms are not well established. As described here, emerging therapies address underlying disease mechanisms by introducing a gene, RNA or other specific molecule with the potential to cure or slow progression of the disease. Recent progress in nanotechnology and nanoscience, particularly regarding particle design and formulation, is expanding disease targets. More secure and efficient drug delivery systems have extended our toolbox for transferring specific molecules, especially into hepatocytes, and led to proof-of-concept studies in animal models. Repurposing existing drugs as molecular chaperones or haem synthesis inhibitors is also promising. This review summarizes key examples of these emerging therapeutic approaches and their application for hepatic and erythropoietic porphyrias.

The effect of different types of microplastic and acute cadmium exposure on the Mytilus galloprovincialis (Lamarck, 1819)

Microplastic (MP) pollution is a pressing issue for both environmental health and the safety of human food sources. This study provides a comprehensive analysis of the effects of MPs on Mediterranean mussels (Mytilus galloprovincialis, Lamarck 1819), focusing on the food safety risks associated with MP and cadmium (Cd) exposure in these organisms intended for consumption. The retention of different polymer types of MPs in mussels was specifically evaluated, and the influence of Cd on MP retention across these polymers was investigated. Mussels were exposed to polystyrene (PS), polypropylene (PP), and polyethylene terephthalate (PET) MPs individually and in combination with the toxic metal Cd for a duration of 7 days. Antioxidant enzymes, oxidative stress parameters, and digestive system enzyme activities, selected as biomarkers for Cd and MPs pollution, were assessed. Furthermore, human consumption risk evaluations and limits regarding mussel intake were analysed in terms of food safety. The results suggest that exposure to Cd, MPs, or their combination induces oxidative stress, tissue damage, and neurotoxicity. Alterations in digestive enzyme activities could impact the mussels' energy acquisition from food and their capacity to conserve energy reserves. The estimated daily intake (EDI), provisional tolerable weekly intake (PTWI), target hazard quotient (THQ), and target cancer risk (TCR) levels for all groups surpassed established limits, implying a significant health risk for humans consuming these products. These results underscore the potential health risks for humans associated with consuming mussels exposed to Cd and/or MPs and provide valuable data for monitoring pollution levels and ecological risks in aquatic organisms. Additionally, our findings reveal that the retention of Cd in mussel tissues varies significantly after exposure, with combinations of PET and Cd showing lower levels of Cd accumulation compared to other groups, suggesting a differential interaction that influences Cd retention.

Altering plasma lipids and liver enzyme activities via hippocampal injections of hen Lysozyme amyloid aggregates in an Alzheimer’s disease mouse model: Insights into the therapeutic role of Bis (Indolyl) phenylmethane

Alzheimer’s disease (AD) is a prevalent form of dementia in the elderly. There is currently no effective treatment available for this disease. Diagnosis of AD typically relies on clinical manifestations and specific biomarkers. The present study investigated the impact of inducing Alzheimer’s disease (AD) in mice through the injection of lysozyme amyloids formed in the presence or absence of Bis (Indolyl) phenylmethane (BIPM) on alterations in plasma lipid profiles and liver enzyme activities. 24 adult Wistar rats were divided into control, Scopolamine, Lysozyme, BIPM groups and the blood samples were obtained from the groups for biochemical analysis. The findings of the study revealed significant changes in the plasma lipid profiles and liver enzyme markers of the Lysozyme group compared to the control group. The Lysozyme group exhibited elevated triglycerides (n = 6, P < 0.02) and LDL levels (n = 6, P < 0.02), reduced HDL (n = 6, P < 0.05) and cholesterol levels (n = 6, P < 0.02), and altered serum glutamic oxaloacetic transaminase (SGOT) level (n = 6, P < 0.05) compared to controls. While the level of serum glutamic pyruvic transaminase (SGPT) did not change significantly compared to the control. BIPM groups showed no significant changes in lipid or enzyme levels compared to controls. Overall, our research has shown that BIPM has the ability to modify the structure of HEWL aggregates, thereby improving the detrimental effects associated with AD caused by these aggregates. Analyzing lipid profiles and liver enzyme markers presents a promising avenue for targeted therapeutic approaches. These alterations observed in the plasma may potentially serve as candidate biomarkers for diagnosing this disease.

Cultivar-specific regulation of antioxidant enzyme activity and stomatal closure confer tolerance of wheat to elevated ozone: A two-year open-field study with five cultivars

Elevated concentrations of tropospheric ozone (O3) pose a significant threat to food production in many regions of the world. We conducted a two-year experiment with five winter wheat (Triticum aestivum L.) cultivars, Yangmai16 (Y16), Yangmai23 (Y23), Zhenmai12 (Z12), Yangmai29 (Y29), and Yangmai30 (Y30), to assess photosynthetic traits, lipid peroxidation, and antioxidant systems under ambient (A-O3) or elevated (E-O3; 1.5 times A-O3) O3 in a Free-Air O3Concentration Enrichment system (FACE). E-O3 accelerated leaf senescence, manifested by marked reductions in photosynthetic rate, stomatal conductance, total antioxidant capacity, and photosynthetic pigment content, accompanied by altered antioxidant enzyme activity and a significant increase in malondialdehyde content (an indicator of lipid peroxidation). Most parameters showed significant inter-cultivar differences, as well as interactions between O3 and cultivar. The response of the antioxidant system in wheat flag leaves was influenced by O3 exposure levels. The response of antioxidant enzymes at the grain filling stage and the timely closure of stomata conferred tolerance to O3. This tolerance was associated with higher antioxidant enzyme activity at the anthesis stage but was not related to the size of stomata. This study provides a crucial theoretical foundation for further breeding O3-tolerant cultivars.

Non-thermal techniques for microbiological safety, nutritional preservation, and enhanced efficiency in dairy processing

The ongoing era of adopted lifestyle among humans involves shortcuts in every aspect, and a similar trend can be observed in food processing and preservation, especially in dairy preparation. Thus, lots of non-thermal processes including high-pressure processing (HPP), ultrasound (US) treatment, pulsed electric fields (PEF), ultraviolet (UV) light and oscillating magnetic fields (OMF), etc. have been invented. By inactivating bacteria, these non-thermal processes keep food's sensory and nutritional quality while also preventing thermal degradation of food components near ambient temperatures. Non-thermal techniques can effectively preserve a food's nutraceuticals and functional potential, while simultaneously ensuring microbiological safety and maintaining the integrity of its bioactive components. During the thermal processing, several heat-labile components of milk and milk products may be lost In contrast, non-thermal processes are gentler compared to thermal treatments, making them preferred choices that avoid compromising nutritional value. It has been observed that non-thermal technology can increase processing efficiency and microstructure through constituent interactions, alteration of enzyme activity, and development of hypoallergenic products. However, in order to use thermal technologies profitably, the risk of operation, equipment cost, technological compatibility, and goal of processing the product must be thoroughly assessed prior to using these processes. Non-thermal processes can also be combined with other strategies like the addition of bio-preservatives or modified atmospheric packaging etc., to enhance the antimicrobial effects. Keywords: Non-thermal processes; Microbiological safety; Dairy processing; Bioactive components; Bioactive compounds; Enzyme activity; Nutritional quality; Bio-preservatives.

Application of poly(L-lactic acid)-based films for equilibrium modified atmosphere packaging of “Kyoho” grapes and its favorable protection for anthocyanins

Grapes were packaged by different Poly (L-lactic acid)-based packaging films (PLTL-PLEL) and stored at 5 °C for 35 days to investigate the effects of equilibrium modified atmosphere packaging on the quality of “Kyoho” grapes during storage. Changes in physiochemical quality, antioxidant content and senescence of grapes were studied. Furthermore, UPLC-Q-TOF-MS/MS was used to observe and identify key factors influencing the variation of grape anthocyanins under different atmosphere conditions. Alterations in gas components and enzyme activities significantly impacted anthocyanin levels, highlighting oxygen concentration as the primary influence on total anthocyanin levels. The PLTL-PLEL50 packaging resulted in an approximate 5.7% lower weight loss and increased soluble solids by approximately 14.4%, vitamin C, total phenols and flavonoids reaching 60.2 mg/100 g, 8.4 mg/100 g and 7.2 mg/100 g, respectively. This packaging also preserved higher anthocyanin levels, with malvidin-3-glucoside and peonidin-3-glucoside at 0.55 μg/mL and 1.62 μg/mL, respectively, on the 35th day of storage.

Joint toxic mechanism of clothianidin and prochloraz in the earthworm (Eisenia fetida)

Pesticides are typically present as combinations within soil ecosystems and have detrimental effects on untamed surroundings. However, the collective impacts and fundamental mechanisms of pesticides on soil living beings are currently inadequately assessed. In our current work, we evaluated the interactive consequences of clothianidin (CLO) and prochloraz (PRO) on earthworms (Eisenia fetida) using several toxicological tests, such as acute adverse effects, biocatalytic activity, and alterations in transcriptional activity. The findings revealed that CLO (with a 14-day LC50 value of 6.08 mg kg−1) exhibited greater toxicity compared to PRO (with a 14-day LC50 value of 79.41 mg kg−1). Moreover, the combinations of CLO and PRO had synergistic acute effects on E. fetida. Additionally, the activities of POD, CAT, and GST were significantly varied in most instances of single and mixed treatments when compared to the control. Surprisingly, the transcriptional levels of four genes (gst, sod, crt, and ann), related to oxidative load, metabolic detoxification systems, endoplasmic reticulum, and oxytocin neuropeptide, respectively, were also altered in response to single and mixture exposures, as compared to the control. Alterations in enzyme activity and gene transcriptional level could serve as early indicators for detecting co-exposure to pesticides. The findings of this research offered valuable holistic understanding regarding the toxicity of pesticide combinations on earthworms. Further research should be conducted to investigate the persistent effects of pesticide mixtures on terrestrial invertebrates in order to draw definitive conclusions about the associated risks.

Effect of Aqueous Solanum macrocarpon Leaves Extract on Hyperglycemia, Liver Enzymes, and Liver and Pancreas Histology in Alloxan-Induced Diabetes

Solanum macrocarpon (SM) is frequently used for both medicinal and dietary purposes. It has been documented to have hypoglycemic properties in diabetes management. This research delved into the effect of aqueous Solanum macrocarpon leaves extract on blood glucose levels, liver enzymes, antioxidant enzymes, and histology of the liver and pancreas in alloxan-induced diabetic rats. A total of thirty male Wistar rats, with weights ranging from 150 to 200 g, were randomly divided into six groups, each containing five rats. The normal (A) and diabetic control (B) groups received distilled water. The diabetic treated groups (C, D, E, and F) were administered 5 mg of glibenclamide, 250 mg/kg, 500 mg/kg, and 750 mg/kg of Solanum macrocarpon extract orally for a period of 14 days. Significant reversal of the altered levels of liver enzymes was noted in the results. Positive alterations in blood glucose concentration and antioxidant enzyme activity were also observed. The histological examination showed damage to the hepatic and pancreatic cells of the diabetic untreated rat group, which was mitigated in diabetic rats treated with the aqueous extract. The findings indicate that the aqueous Solanum macrocarpon leaves extract serves as a valuable source of natural antioxidants, promoting both liver function and blood glucose regulation.

The influence of the model pesticides parathion and paraoxon on human cytochrome P450 and associated oxygenases in HepaRG cells

Introduction Intentional and unintentional organophosphorus pesticide exposure is a public health concern. Organothiophosphate compounds require metabolic bioactivation by the cytochrome P450 system to their corresponding oxon analogues to act as potent inhibitors of acetylcholinesterase. It is known that interactions between cytochrome P450 and pesticides include the inhibition of major xenobiotic metabolizing cytochrome P450 enzymes and changes on the genetic level. Methods In this in vitro study, the influence of the pesticides parathion and paraoxon on human cytochrome P450 and associated oxygenases was investigated with a metabolically competent cell line (HepaRG cells). First, the viability of the cells after exposure to parathion and paraoxon was evaluated. The inhibitory effect of both pesticides on cytochrome P450 3A4, which is a pivotal enzyme in the metabolism of xenobiotics, was examined by determining the dose-response curve. Changes on the transcription level of 92 oxygenase associated genes, including those for important cytochrome P450 enzymes, were evaluated. Results The exposure of HepaRG cells to parathion and paraoxon at concentrations up to 100 µM resulted in a viability of 100 per cent. After exposure for 24 hours, pronounced inhibition of cytochrome P450 3A4 enzyme activity was shown, indicating 50 per cent effective concentrations of 1.2 µM (parathion) and 2.1 µM (paraoxon). The results revealed that cytochrome P450 involved in parathion metabolism were significantly upregulated. Discussion Relevant changes of the cytochrome P450 3A4 enzyme activity and significant alteration of genes associated with cytochrome P450 suggest an interference of pesticide exposure with numerous metabolic processes. The major limitations of the work involve the use of a single pesticide and the in vitro model as surrogate to human hepatocytes. Conclusion The data of this study might be of relevance after survival of acute, life-threatening intoxications with organophosphorus compounds, particularly for the co-administration of drugs, which are metabolized by the affected cytochrome P450.