Holistic assessment of dimethoate toxicity in Carcinus aestuarii's muscle tissues.

Dimethoate (DMT) is one of the most harmful and commonly used organophosphate pesticides in agricultural lands to control different groups of parasitic insects. However, this pesticide is considered a dangerous pollutant for aquatic organisms following its infiltration in coastal ecosystems through leaching. Yet, our investigation aimed to gain new insights into the toxicity mechanism of DMT in the muscles of the green crab Carcinus aestuarii, regarding oxidative stress, neurotransmission impairment, histological aspects, and changes in lipid composition, assessed for the first time on the green crab's muscle. Specimens of C. aestuarii were exposed to 50, 100, and 200 µg DMT L-1 for 24 h. Compared to the negative control group, the higher the DMT concentration, the lower the saturated fatty acids (SFA), and the higher the monounsaturated fatty acids (MUFA). The significant increase in polyunsaturated fatty acid n-6 (PUFA n-6) was related to the high release, mainly, of linoleic acid (LA, C18: 2n6) and arachidonic acid (ARA, C20: 4n6) levels. Biochemical biomarkers showed that DMT exposure promoted oxidative stress, highlighted by increased levels of hydrogen peroxide (H2O2), malondialdehyde (MDA), advanced oxidation protein product levels (AOPP), and protein carbonyl (PCO). Furthermore, the antioxidant defense system was activated, as demonstrated by the significant changes in the enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) levels associated with an adaptation process of C. aestuarii to cope with the DMT exposure. This pesticide significantly impairs the neurotransmission process, as evidenced by the inhibition of acetylcholinesterase (AChE) activity. Finally, several histopathological changes were revealed in DMT-treated crabs, including vacuolation, and muscle bundle loss.This research offered new insights into the toxic mechanism of DMT, pointing to the usefulness of fatty acid (FA) composition as a sensitive biomarker in littoral crabs.

Amino acid HPLC-FLD analysis of spirulina and its protective mechanism against the combination of obesity and colitis in wistar rats.

Objective: The cafeteria diet (CD), designed as an experimental diet mimicking the obesogenic diet, may contribute to the pathogenesis of inflammatory bowel diseases (IBD). This study delves into the influence of spirulina (SP) on obesity associated with colitis in Wistar rats. Methods: The amino acids composition of SP was analyzed using HPLC-FLD. Animals were equally separated into eight groups, each containing seven animals and treated daily for eight weeks as follows: Control diet (SD), cafeteria diet (CD) group, CD + SP (500 mg/kg) and SD + SP. Ulcerative colitis was provoked by rectal injection of acetic acid (AA) (3 % v/v, 5 ml/kg b.w.) on the last day of treatment in the following groups: SD + AA, SD + AA + SP, CD + AA, and CD + AA + SP. Results: Findings revealed that UC and/or CD increased the abdominal fat, weights gain, and colons. Moreover, severe colonic alteration, perturbations in the serum metabolic parameters associated with an oxidative stress state in the colonic mucosa, defined by overproduction of reactive oxygen species (ROS) and increased levels of plasma scavenging activity (PSA). Additionally, obesity exacerbated the severity of AA-induced UC promoting inflammation marked by the overexpression of pro-inflammatory cytokines. Significantly, treatment with SP provided notable protection against inflammation severity, reduced histopathological alterations, attenuated lipid peroxidation (MDA), and enhanced antioxidant enzyme activities (CAT, SOD, and GPX) along with non-enzymatic antioxidants (GSH and SH-G). Conclusions: Thus, the antioxidant effects and anti-inflammatory proprieties of SP could be attributed to its richness in amino acids, which could potentially mitigate inflammation severity in obese subjects suffering from ulcerative colitis. These results imply that SP hold promise as a therapeutic agent for managing of UC, particularly in individuals with concomitant obesity. Understanding SP's mechanisms of action may lead novel treatment strategies for inflammatory bowel diseases and hyperlipidemia in medical research.

Alteration of redox status and fatty acid profile in gills from the green crab (Carcinus aestuarii) following dimethoate exposure.

Dimethoate is a broad-spectrum organophosphate insecticide and acaricide. Through various pathways, such as runoff and drift, dimethoate can reach marine environment, and easily impact common organisms in coastal areas, close to agriculture lands, namely crustaceans. The purpose of this study was to investigate the potential effects of dimethoate exposure (50, 100, and 200 µg/l), for 1 day, on a wide range of markers of oxidative stress and neurotransmission impairment, as well as fatty acids composition and histopathological aspect in the gills of the green crab Carcinus aestuarii. A significant increase in n-3 polyunsaturated fatty acids series, namely the eicosapentaenoic acid (C20: 5n3) and its precursor alpha-linolenic acid (C 18: 3n3) in dimethoate-treated crabs was recorded. Concerning n-6 polyunsaturated fatty acids, we noted a high reduction in arachidonic acid (C20:4n-6) levels. Dimethoate exposure increased the levels of hydrogen peroxide, malondialdehyde, lipid hydroperoxides, protein carbonyl, and caused the advanced oxidation of protein products along with enzymatic and non-enzymatic antioxidant-related markers. Acetylcholinesterase activity was highly inhibited following exposure to dimethoate in a concentration-dependent manner. Finally, deleterious histopathological changes with several abnormalities were noted in exposed animals confirming our biochemical findings. The present study offered unique insights to establish a relationship between redox status and alterations in fatty acid composition, allowing a better understanding of dimethoate-triggered toxicity.

Chromatographic Analyses of Spirulina (Arthrospira platensis) and Mechanism of Its Protective Effects against Experimental Obesity and Hepatic Steatosis in Rats.

Background and Objectives: Obesity is currently a major health problem due to fatty acid accumulation and excess intake of energy, which leads to an increase in oxidative stress, particularly in the liver. The main goal of this study is to evaluate the protective effects of spirulina (SP) against cafeteria diet (CD)-induced obesity, oxidative stress, and lipotoxicity in rats. Materials and Methods: The rats were divided into four groups and received daily treatments for eight weeks as follows: control group fed a standard diet (SD 360 g/d); cafeteria diet group (CD 360 g/d); spirulina group (SP 500 mg/kg); and CD + SP group (500 mg/kg, b.w., p.o.) according to body weight (b.w.) per oral (p.o.). Results: Our results show that treatment with a CD increased the weights of the body, liver, and abdominal fat. Additionally, severe hepatic alteration, disturbances in the metabolic parameters of serum, and lipotoxicity associated with oxidative stress in response to the CD-induced obesity were observed. However, SP treatment significantly reduced the liver alteration of CD feed and lipid profile disorder associated with obesity. Conclusions: Our findings suggest that spirulina has a marked potential therapeutic effect against obesity and mitigates disturbances in liver function parameters, histological alterations, and oxidative stress status.

Marine toxin C17-SAMT causes major structural damage to vital organs in mice following subchronic toxicity trials.

C17-sphinganine analog mycotoxin (C17-SAMT) has been characterized as the contaminant responsible for the atypical toxicity reported in mussels from the Bizerte lagoon (northern Tunisia) over the past decade. C17-SAMT exhibited common symptoms of toxicity in mice, including flaccid paralysis and severe respiratory distress, followed by rapid death. To determine the potential health risks of this neurotoxin, we assessed its subchronic toxicity according to the recommendations of OCDE n° 407. The body weight and the structural changes of vital organs were recorded. Biochemical and hematological parameters were also quantified. Macroscopic observations showed that mice treated with 0.9, 9, and 90 µg/kg C17-SAMT had significantly reduced stomach weights, swollen and fragile intestines, and signs of nephritis with renal abscesses. Transaminase assays pointed out that exposure to C17-SAMT can lead to transaminitis. Above-average lactate dehydrogenase values were recorded in both the treated and satellite groups. Hematology data showed a significant reduction in red blood cell counts in high-dose-treated group. Reductions in hemoglobin and hematocrit were also recorded. Mean leukocyte counts were significantly elevated in the high-, mid-dose treated and satellite groups. At the microscopic level, we noted myocardial atrophy and hyperemia. In the lungs, we noted necrosis associated with macrophages perivascular infiltration and congestion. The kidneys showed mild inflammation and glomerular atrophy. The stomach exhibited mucosal atrophy, while a thin colon and distended small intestine were observed in high-dose-treated group. The liver was affected by vascular congestion, inflammatory infiltration, and lobular necrosis that evolved into acute hepatitis. Lesions, such as inflammatory infiltration and mild necrosis of the liver, cortical abscess with central necrosis in the kidney, and mild congestion of cardiac tissue were recorded in the satellite group.

Dysregulated PDGFR alpha expression and novel somatic mutations in colorectal cancer: association to RAS wild type status and tumor size.

BACKGROUND: Platelet derived growth factor receptor alpha (PDGFRα) has been considered as a relevant factor in tumor proliferation, angiogenesis and metastatic dissemination. It was a target of tyrosine kinase (TK) inhibitors emerged in the therapy of diverse cancers. In colorectal cancer, the commonly used therapy is anti-epithelial growth factor receptor (EGFR). However, both RAS mutated and a subgroup of RAS wild type patients resist to such therapy. The aim of this study is to investigate PDGFRα protein expression and mutational status in colorectal adenocarcinoma and their association with clinicopathological features and molecular RAS status to provide useful information for the identification of an effective biomarker that might be implicated in prognosis and treatment prediction. METHODS: Our study enrolled 103 formalin fixed paraffin-embedded (FFPE) colorectal adenocarcinoma. PDGFRα expression was investigated by immunohistochemistry (IHC). Hotspot exon 18 of PDGFRA was studied by PCR followed by Sanger sequencing and RAS status was determined by real time quantitative PCR. Thirteen normal colon tissues were used as negative controls. RESULTS: PDGFRα staining was detected in the cytoplasm of all tissues. Low expression was observed in all normal colon mucosa. In adenocarcinoma, 45% (45/100) of cases showed PDGFRα overexpression. This overexpression was significantly associated with mutations in exon 18 (P = 0.024), RAS wild type status (P < 10-3), tumor diameter (P = 0.048), whereas there was no association with tumor side (P = 0.13) and other clinicopathological features. CONCLUSION: Overexpression of PDGFRα in adenocarcinoma suggests its potential role in tumor cells growth and invasion. The association between PDGFRα overexpression in both tumor and stromal adenocarcinoma cells with RAS wild type status suggests its potential role in anti-EGFR therapy resistance and the relevance of using it as specific or adjuvant therapeutic target.