Hepatoprotective activity of Lactéol® forte and quercetin dihydrate against thioacetamide-induced hepatic cirrhosis in male albino rats.

Liver cirrhosis is a silent disease in humans and is experimentally induced by many drugs and toxins as thioacetamide (TAA) in particular, which is the typical model for experimental induction of hepatic fibrosis. Thus, the objective of the present study was to elucidate the possible protective effects of lactéol® forte (LF) and quercetin dihydrate (QD) against TAA-induced hepatic damage in male albino rats. Induction of hepatotoxicity was performed by TAA injection (200 mg/kg I/P, twice/ week) in rats. LF (1 × 109 CFU/rat 5 times/week) and QD (50 mg/kg 5 times/week) treated groups were administered concurrently with TAA injection (200 mg/kg I/P, twice/ week). The experimental treatments were conducted for 12 weeks. Hepatotoxicity was evaluated biochemically by measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) in the serum and histopathologically with the scoring of histopathological changes besides histochemical assessment of collagen by Masson's trichrome and immunohistochemical analysis for α-smooth muscle actin (α-SMA), Ki67 and caspase-3 expression in liver sections. Our results indicated that LF and QD attenuated some biochemical changes and histochemical markers in TAA-mediated hepatotoxicity in rats by amelioration of biochemical markers and collagen, α-SMA, Ki67 and caspase3 Immunoexpression. Additionally, LF and QD supplementation downregulated the proliferative, necrotic, fibroblastic changes, eosinophilic intranuclear inclusions, hyaline globules and Mallory-like bodies that were detected histopathologically in the TAA group. In conclusion, LF showed better hepatic protection than QD against TAA-induced hepatotoxicity in rats by inhibiting inflammatory reactions with the improvement of some serum hepatic transaminases, histopathological picture and immunohistochemical markers.

Innovative next-generation therapies in combating multi-drug-resistant and multi-virulent Escherichia coli isolates: insights from in vitro, in vivo, and molecular docking studies.

Despite notable advances in vaccine and antimicrobial therapies, treatment failure has been increasingly reported worldwide. Of note, multi-drug-resistant (MDR) Escherichia coli (E. coli) strains have a considerable share in the evolution of this crisis. So, current practice guidelines are directed towards complementary and alternative therapies. Therefore, we evaluated the antibacterial and antivirulence activities of curcumin, thymol, and eugenol essential oils (EOs) as well as EOs-EOs and EOs-antibiotics interactions on MDR and multi-virulent E. coli isolates. Unfortunately, MDR E. coli could be isolated with a prevalence rate of 95.6% (86/90). Additionally, the majority of our isolates harbored both fimH (95.6%) and ompA (91.1%) genes, and half of them (45/90) were multi-virulent. Interestingly, all the tested EOs, especially curcumin, exhibited inhibitory activities against all MDR and multi-virulent E. coli isolates. The addition of thymol enhanced the antibacterial activities of curcumin and eugenol. Moreover, the activities of piperacillin/tazobactam and imipenem were increased by adding any one of the tested EOs. Regarding the antivirulence activities of the tested EOs, the cell surfaces of treated E. coli isolates under transmission electron microscope (TEM) were uneven. The cells appeared damaged and lost their appendages. Furthermore, EOs strongly reduced the transcription of ompA and fimH genes. The antibacterial and antivirulence activities of the used EOs were confirmed by in silico and mice protection assays. Hereby, we introduced the promising uses of curcumin, thymol, and eugenol oils as complementary and alternative therapies for combating MDR and multi-virulent E. coli isolates. KEY POINTS: • Our promising results confirmed that we were right for renewed interest of EOs. • The EOs, especially curcumin, can be used to prevent treatment failure. • We supposed a new pharmaceutical formulation of antibiotic powders dissolved in EOs.

Interactive effects of dietary quercetin nanoparticles on growth, flesh antioxidant capacity and transcription of cytokines and Aeromonas hydrophila quorum sensing orchestrating genes in Nile tilapia (Oreochromis niloticus).

Recently, the concept of incorporating natural products into nanocarriers has been intended to promote fish growth and health via modulating their stability and bioavailability. In this concern, the potential role of reformulated quercetin into nanocarriers was examined, for the first time, on Nile tilapia's performance and immunity, flesh quality and antioxidant indices and disease resistance. Five hundred fish assigned into five experimental groups with formulated diets containing quercetin nanoparticles (QT-NPs) at levels of 0, 100, 200, 300 and 400 mg/kg were challenged with Aeromonas hydrophila (A. hydrophila) after 12 weeks feeding trial. Fish final body weight gain and feed efficiency were significantly maximized in groups enriched with 300 and 400 mg/kg of QT-NPs. Significant reduction in total saturated fatty acids and an elevation in polyunsaturated fatty acids' contents were noticed in fish fed higher QT-NPs doses. The levels of Hydrogen peroxide, reactive oxygen species and malondialdehyde, the markers of meat antioxidant capacity, were reduced by higher inclusion levels of QT-NPs. Accordingly, serum activities and transcriptional levels of GSH-Px, CAT and SOD genes were increased with elevated QT-NPs levels. Immune responses mediated by upregulation of IL-10 and TGF-ß and downregulation of IL-1ß, IL-8 and TNF-α mRNA levels were found to be positively affected by QT-NPs. Dietary QT-NPs downregulated the expression of ahyI and ahyR quorum sensing genes conferring protection against A. hydrophila challenge. This study concluded that supplementation of quercetin in encapsulated nanoparticles could improve its efficacy making it as a compelling approach to improve fish performance and as a promising drug candidate against A. hydrophila virulence.

Use of fumaric acid as a feed additive in quail's nutrition: its effect on growth rate, carcass, nutrient digestibility, digestive enzymes, blood metabolites, and intestinal microbiota.

To investigate the effects of dietary fumaric acid (FUA) on performance, carcasses, nutrient digestibility, blood metabolites, digestive enzymes, and cecal microbiota in Japanese quail chicks. Three hundred unsexed Japanese quail (1-wk-old) were randomly assigned to 5 groups. Supplementation of FUA in the diet of Japanese quail chicks exhibited a significant improvement in growth performance through the different experimental periods studied compared with those receiving unsupplemented one. The digestibility of crude protein (CP) and metabolizable energy (ME) were improved with 10 and 15 g/kg FUA, respectively. Apart from lipase enzyme, birds fed 5 and 15 g/kg FUA recorded higher activity of amylase. There were no significant changes among experimental groups on the relative weights of carcass, gizzard, heart, and dressing. Dietary supplementation of FUA at different levels (P> 0.05) increased total protein (TP) and globulin (GLB) concentrations and A/G % compared with control group. A significant (P < 0.01) decrease in plasma low density lipoprotein (LDL) and total cholesterol (TC) levels and increase in high density lipoprotein (HDL) concentrations were observed in chicks fed with FUA containing diets. Immunoglobulin G (IgG) (P = 0.0026) and M (IgM) (P = 0.0007) levels were greater in groups treated with either 10 or 15 g FUA/kg diet. A significant increase in plasma Ca concentration was noticed in chicks received 15 g FUA/ kg compared with the other groups. Quail chicks received diets containing FUA at different levels exhibited reduced cecal count of coliform, E. coli, and Salmonella as compared with control group. In conclusion, supplementation of fumaric acid (especially 15 g/kg diet) in quail chick diets improved their growth, digestibility of nutrients, immune response, antioxidant status, digestive enzyme, and intestinal health.

Dietary cinnamaldehyde nanoemulsion boosts growth and transcriptomes of antioxidant and immune related genes to fight Streptococcus agalactiae infection in Nile tilapia (Oreochromis niloticus).

The present study was conducted to investigate the effects of dietary cinnamaldehyde nanoemulsion (CNE) on growth, digestive activities, antioxidant and immune responses and resistance against Streptococcus agalactiae (S. agalactiae) in Nile tilapia. Four experimental diets were formulated containing CNE at levels of 0, 100, 200 and 300 mg/kg diet for 12 weeks. At the end of the experiment, all fish were challenged by S. agalactiae. The results showed that the final body weight was increased in fish groups fed 200 and 300 mg CNE/kg diet by 18.4 and 17.2% with respect to the control group. Moreover, feed conversion ratio and digestive enzymes' activities were improved in groups fed 200 and 300 then 100 mg of dietary CNE/kg diet. Groups fed CNE exhibited a significant increase in serum immune-related parameters when compared with control group. Additionally, the hypocholesterolemic effects was achieved after CNE feeding unlike the control group in a dose dependent manner. With increasing dietary CNE levels, genes expression of cytokines and antioxidant enzymes were upregulated. Less severe adverse clinical symptoms and respectable cumulative mortalities associated with S. agalactiae infection were observed in fish fed CNE. To our knowledge, this study was the first offering a protective effect of CNE against S. agalactiae infection in Nile tilapia with a maximum down-regulation of cylE and hylB virulence genes expression noticed in group fed 300 mg of CNE/kg diet (up to 0.10 and 0.19- fold, respectively). Therefore, the present study recommended that an incorporation of CNE at level of 300 mg/kg diet for Nile tilapia could promote their growth, enhance their immunity and antioxidant status and provide protection against virulent S. agalactiae.

Dietary garlic and chitosan enhanced the antioxidant capacity, immunity, and modulated the transcription of HSP70 and Cytokine genes in Zearalenone-intoxicated European seabass.

The present study was performed to evaluate the toxic effects of feed-born zearalenone (ZEN) on antioxidative status, immunity, transcriptomic responses of European seabass, and the modulating roles of dietary garlic and/or chitosan powders. Fish (30.7 ± 0.6 g) were randomly arranged in five experimental groups (in triplicates), whereas the first group was fed on the control diet only without any supplements (control), and the second group was fed on the basal diet contaminated with ZEN (0.725 mg/kg diet). Three other groups were fed on ZEN-contaminated diets and simultaneously supplemented with garlic powder (GP) (30 g/kg diet) (ZEN + GP), chitosan powder (CH) (10 g/kg diet) (ZEN + CH), and a mixture of GP and CH (ZEN + GP + CH). Fish were fed on the experimental diets thrice a day for 4 weeks. Two-way ANOVA revealed a gradual decline in serum superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities in the ZEN group reaching their lowest levels at the 4th week. Contrariwise, malondialdehyde levels were markedly higher in the ZEN group reaching their highest values at the end of the experiment. A significant decline of total immunoglobulins (P < 0.05) was observed in the serum of the ZEN group, especially after the 4th week. Moreover, significant down-regulation of interleukin-4 (IL-4) and interleukin 1 beta (IL-1ß) genes (P < 0.05) alongside significant up-regulation of tumor necrosis factor-alpha (TNF-α) and heat shock protein 70 (HSP70) genes (P < 0.05) in the liver and anterior kidney of ZEN-intoxicated group. Interestingly, dietary supplementation with GP and CH significantly attenuated ZEN-induced oxidative stress, immunosuppression, and modulated transcriptomic responses of ZEN-exposed fish. Moreover, combined dietary supplementation of both feed additives resulted in better effects than each one alone.

Hypoxia-induced oxidative stress in high altitude population: impact of coenzyme Q10 supplementation.

OBJECTIVE: The aim of this study was to investigate the effect of coenzyme Q10 (CoQ10) supplementation on oxidative stress engendered from hypoxia in population live at high altitude. METHODS: This is an intervention study in which 50 females of volunteers population-36 of them who live at high altitude compared with the placebo group (14 from the total population that live at sea level). Blood samples were collected in -anticoagulant tubes from control and high altitude before and after CoQ10 supplementation (150 mg/day for 2, 4 and 8 weeks). Plasma was separated and used for the determination of malondialdehyde (MDA), nitric oxide (NOx), total antioxidant capacity (TAC), paraoxonase (PON1) by spectrophotometer, CoQ10 and vitamin E by high performance liquid chromatography (HPLC). RESULTS: Our results appeared that TAC, PON1, vitamin E and CoQ10 concentrations were significantly decreased in population at high altitude at base line compared to placebo group population at sea level. Whereas, administration of CoQ10 attenuated all measured parameters especially after eight weeks of administration. CONCLUSION: We concluded that coenzyme Q10 supplement at a dose of 150 mg/day has a powerful effect in oxidative stress parameters and increased antioxidant parameters included vitamin E in population with hypoxia after 4 and 8 weeks. So that supplementation positively affects oxidative stress and is recommended CoQ10 supplementation in population who live at high altitude.

Evaluating the therapeutic potential of one-carbon donors in nonalcoholic fatty liver disease.

Defect in one-carbon metabolism is one of the multiple underlying pathological pathways contributing to NAFLD pathogenesis. Hence, our study was designed to examine whether different one-carbon donors; betaine, choline, and folic acid would possess beneficial effects in NAFLD treatment. Rats were fed with high fat diet and NAFLD rats were orally treated with different doses of betaine or choline or folic acid for 28 days. All used one-carbon donors had dose-dependent ameliorating effects on NAFLD as they succeeded to reduce body and relative liver weights, serum lipids and liver enzymes. These were accompanied by decreasing hepatic fat accumulation and amending hepatic histological structure. They also improved serum and hepatic redox systems (total glutathione (tGSH), reduced GSH, oxidized GSSG, and GSH/GSSG ratio), hepatic S-adenosylmethionine/S-adenosyl homocysteine (SAM/SAH) ratio and increased hepatic global DNA methylation. There were some discrepancies in the dose and the extent of their effect, where folic acid showed the most prominent effects that could be mediated through the significant surge in hepatic SAM/SAH ratio and better efficient correction of one-carbon metabolism than the other donors. Thus, one-carbon donors can be strongly considered in NAFLD management and might influence the whole therapeutic approaches of fatty liver diseases.