High-fat diet-induced aggravation of cardiovascular impairment in permethrin-treated Wistar rats.

This study characterized the impact of post-weaning high-fat diet (HFD) and/or permethrin (PER) treatment on heart dysfunction and fibrosis, as well as atherogenic risk, in rats by investigating interactions between HFD and PER. Our results revealed that HFD and/or PER induced remarkable cardiotoxicity by promoting cardiac injury, biomarker leakage into the plasma and altering heart rate and electrocardiogram pattern, as well as plasma ion levels. HFD and/or PER increased plasma total cholesterol, triacylglycerols, and low-density lipoprotein (LDL) cholesterol levels but significantly reduced high-density lipoprotein (HDL) cholesterol. Cardiac content of peroxidation malonaldehyde, protein carbonyls, and reactive oxygen species were remarkably elevated, while glutathione levels and superoxide dismutase, catalase and glutathione peroxidase activities were inhibited in animals receiving a HFD and/or PER. Furthermore, cardiac DNA fragmentation and upregulation of Bax and caspase-3 gene expression supported the ability of HFD and/or PER to induce apoptosis and inflammation in rat hearts. High cardiac TGF-β1 expression explained the profibrotic effects of PER either with the standard diet or HFD. Masson's Trichrome staining clearly demonstrated that HFD and PER could cause cardiac fibrosis. Additionally, increased oxidized LDL and the presence of several lipid droplets in arterial tissues highlighted the atherogenic effects of HFD and/or PER in rats. Such PER-induced cardiac and vascular dysfunctions were aggravated by and associated with a HFD, implying that obese individuals may be more vulnerable to PER exposure. Collectively, post-weaning exposure to HFD and/or PER may promote heart failure and fibrosis, demonstrating the pleiotropic effects of exposure to environmental factors early in life

Effects of feeding rate and formula fineness degree of ring die pellet mill on mechanical property, physical quality, energy requirements, and production cost of poultry diets

The effect of a machine feeding rate (FR; 1, 1.5 and 2 Mg/h) and/or three levels of selected fineness degree (FD; 3, 5 and 7 mm) on machine performance, pellet physical parameters, required energy and production cost of three main types of broilers diets were examined in this experiment. The examined broiler diets were formulated to meet the Ross 308 strain requirements. A complete factorial design (3×3×3) was used to identify the effects of studied factors on the pellet mill machine and pellet production. The obtained results indicated that the pellet mill productivity significantly (p˂0.001) improved through increased pellet mill feeding rate level. In addition, the machine pelleting efficiency was found to be significantly affected by all studied variables and their interactions. While the total power consumption of the machine showed no variations under the impact of the tested factors or with any of their combinations. Regarding the pellet physical quality indices, all broiler diets with all selected FD and lower FR had the maximum durability and bulk density levels. Furthermore, lower feeding rates were associated with higher hardness degrees. The lowest production costs were substantially correlated with high FR and intermediate FD (5 mm). Furthermore, production costs were determined to be reduced in finisher broiler diets under different feeding rates. Moreover, manufacturing costs of finisher broiler meals were observed to decrease in several feeding rates. Overall, these findings indicate the capabilities of producing high-quality pellets and reducing the needed production costs by optimizing feeding rates to 2 Mg/h and 2 mm fineness in broiler diets

Involvement of Autophagy and Oxidative Stress-Mediated DNA Hypomethylation in Transgenerational Nephrotoxicity Induced in Rats by the Mycotoxin Fumonisin B1

Fumonisin B1 (FB1), a mycotoxin produced by Fusarium verticillioides, is one of the most common pollutants in natural foods and agricultural crops. It can cause chronic and severe health issues in humans and animals. The aim of this study was to evaluate the transgenerational effects of FB1 exposure on the structure and function of the kidneys in offspring. Virgin female Wistar rats were randomly divided into three groups: group one (control) received sterile water, and groups two and three were intragastrically administered low (20 mg/kg) and high (50 mg/kg) doses of FB1, respectively, from day 6 of pregnancy until delivery. Our results showed that exposure to either dose of FB1 caused histopathological changes, such as atrophy, hypercellularity, hemorrhage, calcification, and a decrease in the glomerular diameter, in both the first and second generations. The levels of the antioxidant markers glutathione, glutathione S-transferase, and catalase significantly decreased, while malondialdehyde levels increased. Moreover, autophagy was induced, as immunofluorescence analysis revealed that LC-3 protein expression was significantly increased in both generations after exposure to either dose of FB1. However, a significant decrease in methyltransferase (DNMT3) protein expression was observed in the first generation in both treatment groups (20 mg/kg and 50 mg/kg), indicating a decrease in DNA methylation as a result of early-life exposure to FB1. Interestingly, global hypomethylation was also observed in the second generation in both treatment groups despite the fact that the mothers of these rats were not exposed to FB1. Thus, early-life exposure to FB1 induced nephrotoxicity in offspring of the first and second generations. The mechanisms of action underlying this transgenerational effect may include oxidative stress, autophagy, and DNA hypomethylation

Upregulation of Nrf2/HO-1 Signaling and Attenuation of Oxidative Stress, Inflammation, and Cell Death Mediate the Protective Effect of Apigenin against Cyclophosphamide Hepatotoxicity

Liver injury is among the adverse effects of the chemotherapeutic agent cyclophosphamide (CP). This study investigated the protective role of the flavone apigenin (API) against CP-induced liver damage, pointing to the involvement of Nrf2/HO-1 signaling. Rats were treated with API (20 and 40 mg/kg) for 15 days and received CP (150 mg/kg) on day 16. CP caused liver damage manifested by an elevation of transaminases, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH), and histological alterations, including granular vacuolation, mononuclear cell infiltration, and hydropic changes. Hepatic reactive oxygen species (ROS), malondialdehyde (MDA), and nitric oxide (NO) were increased and glutathione (GSH) and antioxidant enzymes were decreased in CP-administered rats. CP upregulated the inflammatory markers NF-κB p65, TNF-α, IL-6, and iNOS, along with the pro-apoptotic Bax and caspase-3. Pre-treatment with API ameliorated circulating transaminases, ALP, and LDH, and prevented histopathological changes in CP-intoxicated rats. API suppressed ROS, MDA, NO, NF-κB p65, iNOS, inflammatory cytokines, oxidative DNA damage, Bax, and caspase-3 in CP-intoxicated rats. In addition, API enhanced hepatic antioxidants and Bcl-2 and boosted the Nrf2 and HO-1 mRNA abundance and protein. In conclusion, API is effective in preventing CP hepatotoxicity by attenuating oxidative stress, the inflammatory response, and apoptosis. The hepatoprotective efficacy of API was associated with the upregulation of Nrf2/HO-1 signaling