Pulmonary damage induction upon Acrylic amide exposure via activating miRNA-223-3p and miRNA-325-3p inflammasome/pyroptosis and fibrosis signaling pathway: New mechanistic approaches of A green-synthesized extract.

Exposure to acrylic amide (AD) has garnered worldwide attention due to its potential adverse health effects, prompting calls from the World Health Organization for intensified research into associated risks. Despite this, the relationship between oral acrylic amide (acrylamide) (AD) exposure and pulmonary dysfunction remains poorly understood. Our study aimed to investigate the correlation between internal oral exposure to AD and the decline in lung function, while exploring potential mediating factors such as tissue inflammation, oxidative stress, pyroptosis, and apoptosis. Additionally, we aimed to evaluate the potential protective effect of zinc oxide nanoparticles green-synthesized moringa extract (ZNO-MONPs) (10 mg/kg b.wt) against ACR toxicity and conducted comprehensive miRNA expression profiling to uncover novel targets and mechanisms of AD toxicity (miRNA 223-3 P and miRNA 325-3 P). Furthermore, we employed computational techniques to predict the interactions between acrylic amide and/or MO-extract components and tissue proteins. Using a rat model, we exposed animals to oral acrylamide (20 mg/kg b.wt for 2 months). Our findings revealed that AD significantly downregulated the expression of miRNA 223-3 P and miRNA 325-3 P, targeting NLRP-3 & GSDMD, respectively, indicating the induction of pyroptosis in pulmonary tissue via an inflammasome activating pathway. Moreover, AD exposure resulted in lipid peroxidative damage and reduced levels of GPX, CAT, GSH, and GSSG. Notably, AD exposure upregulated apoptotic, pyroptotic, and inflammatory genes, accompanied by histopathological damage in lung tissue. Immunohistochemical and immunofluorescence techniques detected elevated levels of indicative harmful proteins including vimentin and 4HNE. Conversely, concurrent administration of ZNO-MONPs with AD significantly elevated the expression of miRNA 223-3 P and miRNA 325-3 P, protecting against oxidative stress, apoptosis, pyroptosis, inflammation, and fibrosis in rat lungs. In conclusion, our study highlights the efficacy of ZNO-MONPs NPs in protecting pulmonary tissue against the detrimental impacts of foodborne toxin AD.

Comparable bio-evaluation of curcumin and chitosan-encapsulated curcumin nanoparticles against the reprotoxic potential of fenpropathrin pyrethroid in rats: Genomic and morphometric prospectives.

This study delves into the intricate exploration of potential toxic effects resulting from subchronic exposure to fenpropathrin (FNP) on the reproductive system of male SD rats. Adding to the novelty, our study undertakes a pioneering comparison of the effects of curcumin (CUR) and curcumin-encapsulated chitosan nanoparticles (CS.CUR.NPs) on these toxic effects. The study involved a cohort of sixty male SD rats (six groups): vehicle control, CUR, Cs.CUR.NPs, FNP, and two combination groups (FNP with CUR or Cs.CUR.NPs). The synthesized Cs.CUR.NPs nanoparticles underwent meticulous characterization using Fourier Infrared spectroscopy (FT-IR) and transmission electron microscopy (TEM). The findings revealed that FNP caused oxidative stress, sperm abnormalities, reduced motility and sperm count FNP decreased serum LH, FSH, 17-ß estradiol, and testosterone levels. FNP downregulated the mRNA expression of the spermatogenesis and steroidogenesis-related genes, While, downregulated hypothalamic KISS-1 and KISS-1r expression. Histopathological alterations were assessed and scored. Surprisingly, the treatment with CUR and Cs.CUR.NPs exhibited remarkable restorative effects on semen quality, sex hormone levels, antioxidant capacity, and mRNA expression of the targeted genes. Notably, Cs.CUR.NPs displayed superior properties when compared to CUR. Nevertheless, further research is imperative to evaluate their efficacy across various bodily tissues.

Restorative effects of gallic acid against sub-chronic hepatic toxicity of co-exposure to zinc oxide nanoparticles and arsenic trioxide in male rats.

Background and objectives: This study aimed to assess the effect of zinc oxide nanoparticles (ZNPs) and/or arsenic trioxide (ATO) exposure on the liver of adult male Sprague Dawley rats. Moreover, the probable ameliorative impact of gallic acid (GA) against ZNPs and ATO-induced hepatotoxicity and the possible underlying mechanisms were evaluated. Methods: Sixty male Sprague Dawley rats were distributed into six groups. The 1st and 2nd groups were orally given distilled water (1 ml/kg) and 20 mg GA/kg b. wt, respectively. The 3rd and 4th groups were orally given 100 mg ZNPs/kg b. wt and 8 mg ATO/kg b. wt, respectively. The 5th group was co-administered ZNPs and ATO at the doses mentioned above. The last one was co-administered ZNPs, ATO, and GA at the earlier described doses. All tested compounds were orally given once a day for 60 successive days. Then, serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total, direct, indirect bilirubin, triglycerides, total cholesterol, HDL, VLDL, and LDL were estimated. The hepatic content of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) was evaluated. Moreover, Bcl-2 and Bax's reactive proteins were immunohistochemically detected, and Zn and As residual patterns in hepatic tissues were assessed. Results: ZNPs, ATO, and ZNPs+ATO-exposed rats showed significantly (P < 0.001) elevated serum AST (219%, 233%, and 333%), ALT (300%, 400%, and 475%), ALP (169%, 205%, and 294%), and total bilirubin (42%, 68%, and 109%) compared to the control ones. On the other hand, a significantly (P < 0.001) declined SOD (58%, 49%, and 43%) and GPx (70%, 63%, and 56%) but increased MDA (133%, 150%, and 224%) was recorded in the hepatic tissues of ZNPs, ATO, and ZNPs+ATO exposed rats, respectively, relative to the control rats. Moreover, the hepatic tissues of the ZNPs, ATO, and ZNPs+ATO exposed rats showed a significant (P < 0.001) decrease in Bcl-2 (28%, 33%, and 23%) but elevation in Bax (217%, 267%, and 236%) immunoreactivities compared to the control rats. These findings were consistent with the microscopic alterations in the hepatic architecture and accumulation of Zn and As. Furthermore, a notable hyperlipidemic condition was recorded following ZNPs and/or ATO exposure. On the contrary, GA notably reduced hepatic enzymes compared to ZNPs+ATO-exposed rats. Additionally, GA markedly improved ZNPs+ATO-afforded liver tissue damage and apoptotic events. Conclusion: Overall, GA oral dosing significantly mitigated the negative effects of ZNPs and ATO on the liver by improving the antioxidant defense system and controlling apoptotic changes.

Stabilization of glutathione redox dynamics and CYP2E1 by green synthesized Moringa oleifera-mediated zinc oxide nanoparticles against acrylamide induced hepatotoxicity in rat model: Morphometric and molecular perspectives.

The terrible reality is that acrylamide (AA) is a common food contaminant found in a wide variety of commonly consumed foods. This research involves the advancement of a more dependable technique for the bio-fabrication of zinc oxide nanoparticles (ZNPs) through the green method using Moringa Oleifera extract (MO-ZNPs) as an efficient chelating agent for acrylamide (AA). The effects of AA on glutathione redox dynamics, liver function, lipid profile, and zinc residues in Sprague Dawley rats are investigated. Finally, the microarchitecture and immunohistochemical staining of Caspase-3 and CYP2E1 were determined in the liver tissue of rats. Four separate groups, including control, MO-ZNPs (10 mg/kg b. wt), AA (20 mg/kg b. wt), and AA + MO-ZNPs for 60 days. The results revealed a suppressed activity of glutathione redox enzymes (GSH, GPX,and GSR) on both molecular and biochemical levels. Also, AA caused elevated liver enzymes, hepatosomatic index, and immunohistochemical staining of caspase-3 and CYP2E1 expression. MO-ZNPs co-treatment, on the other hand, stabilized glutathione-related enzyme gene expression, normalized hepatocellular enzyme levels, and restored hepatic tissue microarchitectures. It could be assumed that MO-ZNPs is a promising hepatoprotective molecule for alleviating AA-induced hepatotoxicity. We witnessed changes in glutathione redox dynamics to be restorative. Glutathione and cytochrome P450 2E1 play crucial roles in AA detoxification, so maintaining a healthy glutathione redox cycle is necessary for disposing of AA toxicity.

The impact of long-term oral exposure to low doses of acrylamide on the hematological indicators, immune functions, and splenic tissue architecture in rats.

There is a global increase in daily dietary intake of acrylamide (ACR) owing to its presence in various foods. However, several toxicological issues are still unclear, particularly after oral exposure to low doses for long durations. As a result, the objective of this research was to investigate the effects of giving male Wistar rats two dosages of ACR (1 or 2 mg/kg b.wt.) via oral gavage once a day for 90 days on blood components, immune markers, and splenic tissue. The results revealed that leukopenia, lymphocytopenia, eosinophilia, and thrombocytopenia were all found to be ACR dose-dependent. In addition, ACR-treated rats had considerably higher IgG and IgM levels. Following ACR exposure, phagocytic activity, lysozyme, and nitric oxide levels were significantly reduced. In ACR-exposed rats, there was a significant reduction in lymphocyte proliferation but an increase in LDH activity. Both splenic tissue and bone marrow showed a variety of degenerative changes. There was a significant increase in CD4+ and CD8+ immunolabeling. Rats exposed to ACR at both levels showed a significant rise in comet variables. Overall, our findings suggested that long-term exposure to ACR could cause hematological disorders, DNA damage, and disturbances of immune functions.

Chitosan-Stabilized Selenium Nanoparticles and Metformin Synergistically Rescue Testicular Oxidative Damage and Steroidogenesis-Related Genes Dysregulation in High-Fat Diet/Streptozotocin-Induced Diabetic Rats.

BACKGROUND: this study examined the metformin (MF) and/or chitosan stabilized selenium nanoparticles (CH-SeNPs) efficacy to alleviate the male reproductive function impairment in a high-fat diet feed with low-dose streptozotocin (HFD/STZ) induced type 2 diabetes mellitus (T2DM) diabetic rat model. METHODS: control non-diabetic, HFD/STZ diabetic, HFD/STZ+MF, HFD/STZ+CH-SeNPs, and HFD/STZ+MF+CH-SeNPs rat groups were used. After 60 days, semen evaluation, hormonal assay, enzymatic antioxidant, lipid peroxidation, testis histopathology, and the steroidogenesis-related genes mRNA expressions were assessed. RESULTS: in the HFD/STZ diabetic rats, sperm count and motility, male sexual hormones, and testicular antioxidant enzymes were significantly reduced. However, sperm abnormalities and testicular malondialdehyde were significantly incremented. The steroidogenesis-related genes, including steroidogenic acute regulatory protein (StAr), cytochrome11A1 (CYP11A1), cytochrome17A1 (CYP17A1), and hydroxysteroid 17-beta dehydrogenase 3 (HSD17B3), and the mitochondrial biogenesis related genes, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGCα) and sirtuin (SIRT), were significantly downregulated in the HFD/STZ diabetic rats. However, CYP19A1mRNA expression was significantly upregulated. In contrast, MF and/or CH-SeNPs oral dosing significantly rescued the T2DM-induced sperm abnormalities, reduced sperm motility, diminished sexual hormones level, testicular oxidative damage, and steroidogenesis-related genes dysregulation. In the MF and CH-SeNP co-treated group, many of the estimated parameters differ considerably from single MF or CH-SeNPs treated groups. CONCLUSIONS: the MF and CH-SeNPs combined treatment could efficiently limit the diabetic complications largely than monotherapeutic approach and they could be considered a hopeful treatment option in the T2DM.

Antimicrobial and antioxidant properties of chitosan and its derivatives and their applications: A review.

In this era, there is a global concern in the use of bioactive molecules such as chitosan in the field of antimicrobial and antioxidant benefits. Because of its biodegradability, biological compatibility, antimicrobial, antioxidants activity, and high safety, chitosan could be used in a large number of applications. It could exist in many forms, such as fibers, gels, films, sponges, nanoparticles, and beads. The different biological activities of chitosan and its products are extensively investigated to broaden the application fields in several areas. Chitosan's natural properties depend strongly on water and other solvent solubility. Consequently, the chitosan oligosaccharides with a low polymerization degree are getting significant attention in the pharmaceutical and medical applications because they have lower viscosity and higher water solubility than chitosan. The objective of this review article is to put the antioxidant and antimicrobial properties of chitosan and its derivatives under the spotlight. The impacts of chitosan on physicochemical parameters like molecular weight and deacetylation degree on its bioactivities are also identified. Additionally, other applications of chitosan and its derivatives, including wound healing products, wastewater treatment, and cosmetics, have also been highlighted.

Melamine and curcumin enriched diets modulate the haemato-immune response, growth performance, oxidative stress, disease resistance, and cytokine production in oreochromis niloticus.

Currently, feed adulteration and contamination with melamine (MEL) are considered one of the serious issues in the aquatic industry. With the limited studies of MEL exposure alone in fish, its adverse impacts on fish cannot be evaluated well. Accordingly, this study aimed to investigate the effects of MEL containing diets on the immune response, disease resistance to Aeromonas hydrophila, growth performance, chemical composition, immune-related genes expression, and histopathology of both spleen and head kidneys. Also, the efficacy of curcumin (CUR) dietary supplementation to alleviate MEL negative impacts were evaluated. A total of 180 apparently healthy Oreochromis niloticus (O. niloticus) were divided into four groups with three replicates fed the basal diet only, basal diet fortified with 200 mg/kg CUR, basal diet containing 1 % MEL, or a basal diet containing CUR + MEL. The results displayed that MEL significantly reduced growth performance indices and body crude lipid contents. Anemic, leukopenic, lymphocytopenic, heterocytopenic, esonipenic, hypoproteinemic and hypoalbuminic conditions were apparent. Moreover, depleted immune and antioxidant indicators including lysozyme activity, nitric oxide, immunoglobulin M, complement 3, glutathione peroxidase, and superoxide dismutase enzyme activity were recorded. Also, MEL reduced the disease resistance of O. niloticus to bacterial infection. Furthermore, MEL induced downregulation of mRNA levels of interleukin 1ß and tumor necrosis factor α in the spleen together with obvious pathological perturbations in both spleen and head kidneys. The CUR addition resulted in a significant enhancement in most indices. These results may conclude that MEL could alter both innate and adaptive immune responses via the negative transcriptional effect on immune-related genes together with the oxidative damage of the immune organs. Furthermore, CUR dietary supplements could be advantageous for mitigating MEL negative impacts, thus offering a favorable aquafeed additive for O. niloticus.

Spirulina platensis attenuates furan reprotoxicity by regulating oxidative stress, inflammation, and apoptosis in testis of rats.

Furan is a common food contaminant and environmental pollutant. Spirulina platensis (SP) is a blue-green algae extensively used as therapeutic and health supplements. This study aimed to explore the probable beneficial role of SP against the influence of furan on reproductive system of male rats. Adult male rats were divided into control, vehicle control, SP (300 mg/kg bwt/ day, 7 days), furan (16 mg/kg bwt/ day,30 day), SP/furan, furan/SP and furan+SP groups. Hematology, sperm count, sperm morphology, serum testosterone (TES), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol (E2) levels, reduced glutathione (GSH), malondialdehyde (MDA), testicular enzymes, and pro inflammatory cytokines were estimated. In addition, histopathology of testis and seminal vesicles and apoptosis were evaluated. Anaemia, leukocytosis, and reduced gonadosomatic index were observed in the furan treated group. TES, LH, FSH, E2, and GSH were significantly decreased following furan treatment. MDA, testicular enzymes, and pro inflammatory cytokines were significantly incremented in testis of furan treated rats. Furan induced apoptic changes in testis. SP significantly counteracted furan reprotoxic impacts, particularly at co-exposure. Conclusively, these findings verified that SP could be candidate therapy against furan reprotoxic impacts.