Modulatory effect of thymol on the immune response and susceptibility to Aeromonas hydrophila infection in Nile tilapia fish exposed to zinc oxide nanoparticles.

Zinc oxide nanoparticles (ZnO-NPs) have many exciting properties that make their use in a continuous increase in various biomedical, industrial, and agricultural applications. This is associated with accumulation in the aquatic ecosystems and fish exposure with consequent deleterious effects. To determine the potential of thymol to counteract the immunotoxic effects of ZnO-NPs, Oreochromis niloticus was exposed to ZnO-NPs (⅕ LC50 =1.14 mg/L, for 28 days) with or without feeding a thymol-incorporated diet (1 or 2 g/kg diet). Our data demonstrated a reduction of aquaria water quality, leukopenia, and lymphopenia with a decrease in serum total protein, albumin, and globulin levels in exposed fish. At the same time, the stress indices (cortisol and glucose) were elevated in response to ZnO-NPs exposure. The exposed fish also revealed a decline in serum immunoglobulins, nitric oxide, and the activities of lysozyme and myeloperoxidase, in addition to reduced resistance to the Aeromonas hydrophila challenge. The RT-PCR analysis showed downregulation of antioxidant (SOD) superoxide dismutase and (CAT) catalase gene expression in the liver tissue with overexpression of the immune-related genes (TNF-α and IL-1ß). Importantly, we found that thymol markedly protected against ZnO-NPs-induced immunotoxicity in fish co-supplemented with thymol (1 or 2 g/kg diet) in a dose-dependent manner. Our data confirm the immunoprotective and antibacterial effects of thymol in ZnO-NPs exposed fish, supporting the potential utility of thymol as a possible immunostimulant agent.

Immunosuppressive Effects of Thallium Toxicity in Nile Tilapia Fingerlings: Elucidating the Rescue Role of Astragalus membranaceus Polysaccharides.

This study evaluated the immunotoxic effects of thallium (Tl) in Nile tilapia fingerlings and the recovery role of dietary Astragalus membranaceus polysaccharides (ASs). An 8-week experiment was designed where 180 fishes were randomly and equally assigned in triplicates into the six groups: the control group (CNT) was reared in unpolluted water and fed a commercial diet, two groups were fed a well-balanced commercial diet plus 1.5 and 3.0 g AS/kg diet (AS0.15 and AS0.30), respectively, the fourth group was exposed to a sublethal dose of Tl (41.9 µg l-1) [equal to 1/10 of 96-h lethal concentration 50 (LC50)], and the last two groups were fed 0.15 and 0.3% AS, respectively, and concurrently exposed to Tl (41.9 µg l-1) (AS0.15+Tl and AS0.30+Tl). Fish hematobiochemical parameters, serum immunity [nitric oxide, total immunoglobulin M (IgM) levels, and lysozyme activity], transcription of hepatic interferon-γ (IFN-γ), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α), and resistance to Aeromonas hydrophila (A. hydrophila) were assessed. Hematobiochemical parameters and serum immune indices were significantly decreased in the fish group exposed to sublethal Tl concentration compared to the CNT group. Furthermore, Tl exposure significantly induced overexpression of IL-1ß, TNF-α, and IFN-γ genes (4.22-, 5.45-, and 4.57-fold higher, respectively) compared to CNT values. Tl exposure also increased the cumulative mortality (%) in Nile tilapia challenged with A. hydrophila. Remarkably, the groups fed AS0.15+Tl and AS0.30+Tl significantly ameliorated all the aforementioned parameters, but did not reach CNT values. Our findings suggest the possible immunomodulating roles of dietary AS in recovering the immunotoxic effects of Tl in Nile tilapia. We can conclude that dietary AS would be useful for maintaining the immunity of Nile tilapia fingerlings.

Thiacloprid Induced Developmental Neurotoxicity via ROS-Oxidative Injury and Inflammation in Chicken Embryo: The Possible Attenuating Role of Chicoric and Rosmarinic Acids.

Insecticides are widely employed in agriculture to control pests and as major factors for enhancing crop productivity. Thiacloprid (TH) is one of the most-used insecticides worldwide. In this study, the negative impact of TH on the brain tissue of developing chicken embryo models and the modulatory effect of chicoric (CA) and rosmarinic (RA) acids were investigated. The eggs were injected in ovo with different doses of TH (0.1, 1, 10, and 100 µg/egg). TH significantly increased the oxidative damage in the brain of exposed embryos in a dose-dependent manner (p < 0.05). TH significantly elevated the oxidative stress markers; protein carbonyl, malondialdehyde content, and DNA damage (p < 0.05). Myeloperoxidase activity and nitric oxide significantly increased with overexpression of the pro-inflammatory cytokines (interferon gamma, tumor necrosis factor alpha, and interleukin-1 beta) and stress-related and apoptotic genes (NF-KB, Caspase-3) in the brain tissue on both biochemical and molecular levels (p < 0.05), while downregulating the expression of antiapoptotic Bcl-2. Co-treatment of CA and RA with TH markedly decreased the insecticide-induced toxicity with a prominent synergistic effect (p < 0.05). In conclusion, TH is suggested to be a possible neurotoxic to embryos of vertebrates including human. The study also revealed the antioxidant, anti-inflammatory, genoprotective, and antiapoptotic property of CA and RA against TH toxicity.

Astaxanthin Mitigates Thiacloprid-Induced Liver Injury and Immunotoxicity in Male Rats.

Thiacloprid (TCP) is a widely used neonicotinoid insecticide with a probable toxic hazard to animals and human beings. This hazard has intensified the demand for natural compounds to alleviate the expected toxic insults. This study aimed at determining whether astaxanthin (ASX) could mitigate the hepatotoxic effect of TCP and diminish its suppressive effect on immune responses in rats. Animals received TCP by gavage at 62.1 mg/kg (1/10th LD50) with or without ASX at 40 mg/kg for 60 days. Intoxicated rats showed modulation of serum transaminases and protein profiles. The hemagglutination antibody titer to sheep red blood cells (SRBC) and the number of plaque-forming cells in the spleen were reduced. The cell-mediated immunity and phagocytosis were suppressed, while serum interleukins IL-1ß, IL-6, and IL-10 were elevated. Additionally, malondialdehyde, nitric oxide, and 8-hydroxy-2'-deoxyguanosine levels were increased in the liver, spleen, and thymus, with depletion of glutathione and suppression of superoxide dismutase and catalase activities. The expressions of inducible nitric oxide synthase and the high mobility group box protein 1 genes were upregulated with histomorphological alterations in the aforementioned organs. Cotreatment with ASX markedly ameliorated the toxic effects of TCP, and all markers showed a regression trend towards control values. Collectively, our data suggest that the protective effects of ASX on the liver and immune system of TCP-treated animals depend upon improving the antioxidant status and relieving the inflammatory response, and thus it may be used as a promising therapeutic agent to provide superior hepato- and immunoprotection.

Astragalus membranaceus polysaccharides modulate growth, hemato-biochemical indices, hepatic antioxidants, and expression of HSP70 and apoptosis-related genes in Oreochromis niloticus exposed to sub-lethal thallium toxicity.

A 60-day experiment was performed to assess the efficacy of dietary Astragalus membranaceus polysaccharides (ASP) in attenuation of sub-lethal thallium (Tl) toxicity in Nile tilapia. Six experimental groups (in triplicates) were designed where a fish group was raised in clean water and fed basal diet and served as control (CONT), two groups were fed the basal diet supplemented with 0.15% and 0.30% ASP (ASPL and ASPH), Tl-intoxicated group exposed to 1/10 of 96-h LC50 (= 41.9 µg/L), and two other groups were fed 0.15% and 0.30% ASP and concomitantly exposed to 41.9 µg Tl/L (ASPL-Tl and ASPH-Tl). At the end of the experiment, fish behavioral responses, clinical signs, survivability, growth, whole-body composition, intestinal digestive enzymes, serum biochemical parameters, hepatic antioxidative biomarkers, and transcription of stress and apoptosis genes were assessed. Results showed that the whole-body composition, intestinal α-amylase and protease enzymes, serum AST and blood urea levels, and hepatic GSH were not significantly different among groups (P > 0.05). The Tl-intoxicated fish group was off food, had darkened skin, showed restlessness and hyperexcitability, and high mortalities. FBW, WG, SGR and FI were significantly decreased alongside increase FCR in the Tl-exposed group. Tl exposure caused significant increases (P < 0.05) in intestinal lipase enzyme and serum indices such as ALT, creatinine, total cholesterol, triglycerides, glucose, and cortisol levels. Moreover, a significant decreases in hepatic CAT and SOD enzyme activities and significant increases in hepatic MDA contents were also noticed (P < 0.05). Furthermore, Tl exposure induced significant upregulation of hepatic HSP70 and apoptosis-related genes (p53 and caspase 3). Interestingly, dietary supplementation with ASP in ASPL-Tl and ASPH-Tl groups modulated the parameters mentioned above but still not reached the CONT values. Altogether, this study suggests that ASP could be beneficial in the modulation of sub-lethal Tl toxicity effects in Nile tilapia. Additionally, we can conclude that using natural feed supplements such as ASP in aquafeed might be necessary for maintaining the overall health performances of Nile tilapia.

Immune response and susceptibility of Nile tilapia fish to Aeromonas hydrophila infection following the exposure to Bifenthrin and/or supplementation with Petroselinum crispum essential oil.

Bifenthrin (BF) is a widely used 3rd generation type I pyrethroid with a potential toxic effect in fish. Nevertheless, its effect on the immune system remains unclear. In the present study, Oreochromis niloticus was exposed to BF at 0.68 µg/L for 60 days, followed by evaluating the hematological, biochemical, and immunological responses. Additionally, the potential of parsley (Petroselinum crispum) essential oil (PEO) to ameliorate the BF-induced toxic insults was explored. Our data have shown reductions in the growth performance with alterations observed in the hematological variables, protein profile and serum biomarkers of stress. DNA oxidative damage was evidenced by elevation of serum 8-hydroxy-2-deoxyguanosine (8-OHdG) content. BF-exposed fish presented also decline in serum lysozyme activity and levels of immunoglobulins (IgG and IgM) and nitric oxide (NO), with diminished resistance to Aeromonas hydrophila challenge. Furthermore, the RT-PCR analysis showed an upregulated expression pattern of immune -related genes including interleukin 1ß (IL-1ß), interferon - γ (IFN-γ) and tumor necrosis factor - α (TNF-α) genes in the liver tissue. Dietary co-supplementation of PEO at 1 or 2 mL/kg diet with concomitant BF exposure, alleviated the adverse effects of the insecticide in a dose-dependent manner. The observations from this study demonstrate the immunomodulation by BF and provide further insight into the protective properties of PEO and strengthen its applicability as a promising feed supplement to fish.

The efficiency of pomegranate (Punica granatum) peel ethanolic extract in attenuating the vancomycin-triggered liver and kidney tissues injury in rats.

This study evaluated the potential of Punica granatum peel ethanol extract (PPEE) in attenuating the liver and kidney tissue injury induced by vancomycin (VM) treatment in rats. Fifty rats were distributed equally into five groups: control group, PPEE-administered group (100 mg/kg BW/day for 2 weeks; orally), VM-treated group (443.6 mg/kg BW, every alternate day for 2 weeks; intraperitoneally), pre-treated group, and concomitant-treated group. The biochemical response and the histopathology of the hepatic and renal tissue of the treated animals were assessed. The results showed that VM treatment induced substantial hepatotoxicity and nephrotoxicity, evidenced by a significant elevation in tissue injury and lipid oxidative (malondialdehyde) and inflammatory response (C-reactive protein) biomarkers, with lowered antioxidants and protein levels. Additionally, VM treatment induced various morphological, cytotoxic, vascular, and inflammatory perturbations as well as upregulation in the immune-expression of Caspase-3 and downregulation of BCL-2. Moreover, PPEE co-treatment was found to reduce the VM-induced toxicity by protecting the tissue against reactive oxygen species (ROS)-mediated oxidative damage, and inflammation as well as hinder the apoptotic cell death by modulating the expression of apoptosis-related proteins. Thus, we conclude that the PPEE administration showed more restoring efficacy when administered prior to VM medication.

Moringa oleifera ethanolic extract attenuates tilmicosin-induced renal damage in male rats via suppression of oxidative stress, inflammatory injury, and intermediate filament proteins mRNA expression.

Tilmicosin (Til) is a popular macrolide antibiotic, widely used in veterinary practice. The present study was designed to address the efficacy of Moringa oleifera ethanolic extract (MOE) in protecting against Tilmicosin (Til) - induced nephrotoxicity in Sprague Dawley rats. Animals were treated once with Til (75 mg/kg bw, subcutaneously), and/or MOE for 7 days (400 or 800 mg/kg bw, by oral gavage). Til-treatment was associated with significantly increased serum levels of creatinine, urea, sodium, potassium and GGT activity, as well as decreased total protein and albumin concentrations. Renal tissue hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels were elevated, while the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes were diminished. The levels of renal tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß) and the mRNA expression of intermediate filament protein encoding genes (desmin, nestin and vimentin) in the kidney were up- regulated with histopathological alterations in renal glomeruli, tubules and interstitial tissue. These toxic effects were markedly ameliorated by co-treatment of MOE with Til, in a dose dependent manner. Taken together, these results indicate that MO at 800 mg/kg protects against Til-induced renal injury, likely by its potent antioxidant and anti-inflammatory properties, which make it suitable to be used as a protective supplement with Til therapy.

Influence of Feeding Quinoa (Chenopodium quinoa) Seeds and Prickly Pear Fruit (Opuntia ficus indica) Peel on the Immune Response and Resistance to Aeromonas sobria Infection in Nile Tilapia (Oreochromis niloticus).

In recent times, nutraceuticals have been used extensively to identify promising feed additives for the improvement of the aquaculture industry through the enhancement of growth and survival rates, potentiation of the immune responses, and fortification of the resistance against infectious bacterial diseases. In this study, Nile tilapia (Oreochromis niloticus) were fed with diets supplemented with quinoa seeds (QU) or prickly pear fruit peel (PP) at the dose levels of 10% or 20% of the diet. After 45 days of the feeding trial, the fish were exposed to Aeromonas sobria (A. sobria) challenge. The pre-challenge indices indicated that both supplements mediated a significant improvement in most of the estimated parameters, including survival rate, antioxidant status, hematological and immunological indices, and hepatoprotective potential. These effects were recorded in the groups fed with high doses of the supplements (20%). The least changes were observed in the QU10-supplemented fish. In the spleen tissue, the TGF-ß gene was upregulated in the PP10-, PP20- and QU20-supplemented groups, while the expression of the IFN-γ gene remained unaffected in all the supplemented groups, except for the PP20-supplemented group, which showed an upregulation. After the challenge with A. sobria, the relative survival percentage was improved by the supplementation of PP and QU, particularly in the PP20-supplemented group, possibly via the promotion of immunological responses, hepatoprotective potency, and modulation of the studied genes. Moreover, the morphological structure of the tissues showed marked recovery. The findings suggest that Nile tilapia fed with different levels of PP peel and QU seeds, particularly at the level of 20%, enhanced the immune response in fish and improved their resistance against A. sobria infection.

The role of sulpiride in attenuating the cardiac, renal, and immune disruptions in rats receiving clozapine: mRNA expression pattern of the genes encoding Kim-1, TIMP-1, and CYP isoforms.

The present study was aimed to explore the cardio-, immuno-, and nephrotoxic effects of the antipsychotic agent clozapine (CLZ) and the alleviative potency of sulpiride (SPD) on these impairments in rats. For this purpose, 40 male rats were divided into four groups and were orally treated with saline (control), CLZ (0.5 mg/kg bw), SPD (28 mg/kg bw), or a combination of CLZ and SPD (CLZ+SPD), daily for 30 consecutive days. At necropsy, blood samples and specimens from the heart, kidneys, and spleen were collected for biochemical, molecular, and histopathological investigations. The results showed that CLZ administration was associated with significantly lower immune status indices and increased serum levels of pro-inflammatory cytokines, lactate dehydrogenase, malondialdehyde, cardiac, and renal tissues injury markers. Moreover, the mRNA expression levels of Kidney Injury Molecule-1 (Kim-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and cytochrome P450 (CYP) isoforms were markedly upregulated in CLZ-treated rats, compared to the control group. On the other hand, rats treated with SPD alone showed non-significant differences in terms of immune response indices, tissue injury markers, and mRNA expression levels of Kim-1, TIMP-1, and CYP isoforms. Finally, CLZ+SPD co-treatment significantly modulated almost all biochemical indices. Besides, Kim-1, TIMP-1, and CYP2C19 mRNA expression levels were significantly downregulated, while other CYP isoforms showed no modulation, compared with CLZ-treated group. Histopathologically, CLZ-treated rats showed severe lesions in renal, splenic, and cardiac tissues, compared with control rats, which were restored in CLZ+SPD-co-treated rats. Overall, these findings demonstrate that CLZ treatment induces significant cardiac, immune, and nephropathic alterations, which were reduced with CLZ+SPD co-treatment.

Moringa oleifera leaves ethanolic extract influences DNA damage signaling pathways to protect liver tissue from cobalt -triggered apoptosis in rats.

This study assessed the potential of Moringa oleifera leaves ethanol extract (MLEE) in attenuating the detrimental effects of cobalt dichloride (CoCl2) on rat liver. Forty rats were assigned to five equal groups: control group, MLEE-treated group, CoCl2-treated group, prophylaxis co-treated group, and therapeutic co-treated group. The levels of Co, hepatic injury markers, total antioxidant capacity (TAC), and oxidative stress biomarkers (reactive oxygen species [ROS] and protein carbonyl [PC]) were evaluated. Comet assay was used to evaluate the extent of DNA damage. Further, the expression profile of DNA-damage effector genes was assayed by real-time quantitative polymerase chain reaction (qRT-PCR) analysis. Immunohistochemical analysis of heat shock protein (HSP-70) in hepatocytes was conducted. The results showed that the exposure of CoCl2 to rats resulted in declined TAC, elevated oxidative injury, and induced DNA damage markers. Upregulation of mRNA expression of tumor suppressor protein (P53), apoptosis inducing factor (AIF), and apoptotic peptidase activating factor 1 (Apaf-1) was observed. The immunostaining density of HSP-70 expression was found to be elevated. Thus, MLEE reduced the CoCl2-induced genotoxicity by preventing CoCl2-induced generation of ROS, and protected against ROS mediated-oxidative injury and DNA damage. Moreover, the expression of DNA damage effector genes was affected. Based on these results, we conclude that MLEE is more effective when administered as a prophylactic regimen with the exposure to CoCl2.

Ethanolic Extract of Moringa oleifera Leaves Influences NF-κB Signaling Pathway to Restore Kidney Tissue from Cobalt-Mediated Oxidative Injury and Inflammation in Rats.

This study aimed to describe the protective efficacy of Moringa oleifera ethanolic extract (MOEE) against the impact of cobalt chloride (CoCl2) exposure on the rat's kidney. Fifty male rats were assigned to five equal groups: a control group, a MOEE-administered group (400 mg/kg body weight (bw), daily via gastric tube), a CoCl2-intoxicated group (300 mg/L, daily in drinking water), a protective group, and a therapeutic co-administered group that received MOEE prior to or following and concurrently with CoCl2, respectively. The antioxidant status indices (superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)), oxidative stress markers (hydrogen peroxide (H2O2), 8-hydroxy-2-deoxyguanosine (8-OHdG), and malondialdehyde (MDA)), and inflammatory response markers (nitric oxide (NO), tumor necrosis factor (TNF-α), myeloperoxidase (MPO), and C-reactive protein (CRP)) were evaluated. The expression profiles of pro-inflammatory cytokines (nuclear factor-kappa B (NF-kB) and interleukin-6 (IL-6)) were also measured by real-time quantitative polymerase chain reaction (qRT-PCR). The results showed that CoCl2 exposure was associated with significant elevations of oxidative stress and inflammatory indices with reductions in the endogenous tissue antioxidants' concentrations. Moreover, CoCl2 enhanced the activity of the NF-κB inflammatory-signaling pathway that plays a role in the associated inflammation of the kidney. MOEE ameliorated CoCl2-induced renal oxidative damage and inflammatory injury with the suppression of the mRNA expression pattern of pro-inflammatory cytokine-encoding genes. MOEE is more effective when it is administered with CoCl2 exposure as a prophylactic regimen. In conclusion, MOEE administration exhibited protective effects in counteracting CoCl2-induced renal injury in rats.

Protective potency of Astragalus polysaccharides against tilmicosin- induced cardiac injury via targeting oxidative stress and cell apoptosis-encoding pathways in rat.

Tilmicosin (Til) was purposed to be used in the treatment of a wide range of respiratory diseases in livestock. However, undesirable adverse effects, cardiac toxicity, in particular, may be associated with Til therapy. In the present study, the response of adult rats administered Til subcutaneously at different doses (10, 25, 50, 75, and 100 mg/kg b.w.; single injection) was evaluated. Astragalus polysaccharide (AP) at two doses (100 and 200 mg/kg b.w.; intraperitoneally) was investigated for its potential to counteract the cardiac influences, involving the oxidative stress-induced damage and apoptotic cell death, elicited by the Til treatment at a dose of 75 mg/kg b.w. in rats. Til induced mortalities and altered the levels of the biomarkers for the cardiac damage, particularly in the rats treated with the doses of 75 and 100 mg/kg b.w.; similarly, morphological alterations in cardiac tissue were seen at all studied doses. AP was found to cause a significant (P Ë‚ 0.05) decline in the levels of impaired cardiac injury markers (troponin, creatine phosphokinase, and creatine phosphokinase-MB), improvement in the antioxidant endpoints (total antioxidant capacity), and attenuation in the oxidative stress indices (total reactive oxygen species, 8-hydroxy-2-deoxyguanosine, lipid peroxides [malondialdehyde], and protein carbonyl), associated with a significant (P Ë‚ 0.05) modulation in the mRNA expression levels of the encoding genes (Bcl-2, Bax, caspase-3, P53, Apaf-1, and AIF), related to the intrinsic pathway of apoptotic cell death in the cardiac tissue. AP administration partially restored the morphological changes in the rat's heart. The highest protective efficacy of AP was recorded at a dose level of 200 mg/kg b.w. Taken together, these results indicated that AP is a promising cardioprotective compound capable of attenuating Til-induced cardiac impact by protecting the rat cardiac tissue from Til-induced apoptosis when administered concurrently with and after the Til injection.

Dual immunological and oxidative responses in Oreochromis niloticus fish exposed to lambda cyhalothrin and concurrently fed with Thyme powder (Thymus vulgaris L.): Stress and immune encoding gene expression.

The present study was performed to explore the immunotoxicological effects of the lambda cyhalothrin (LCH) insecticide and evaluate the efficiency of Thyme powder (TP) as a fish supplement in attenuation of LCH impact on Oreochromis niloticus (O. niloticus) fish. Fish was sampled following 30-days exposure to LCH (1/6 LC50: 0.48 µg/L) and TP (2%) supplementation, individually or in combination. The growth performance, immune status, biochemical indices, and mRNA expression pattern changes of stress and immune-encoding genes in the liver and spleen tissues, respectively, through real-time polymerase chain reaction (RT-PCR) analysis, were evaluated. The findings showed that LCH exposure caused a significant lowering in most of the estimated variables including growth performance, hematological and immunological indices. Moreover, LCH disrupted the oxidant/antioxidant status and dysregulated the expression of stress and immune-related genes, downregulating the mRNA transcript level of Immunoglobulin M heavy chain (IgM), Interferon (IFN-γ), CXC-chemokine, and Toll-like receptors (TLR-7) in the spleen. However, mRNA expression of Myxovirus resistance (Mx) gene remained unaffected. In liver tissue, the heat shock protein (HSP-70) expression was upregulated, while that of cytochrome P450 1A (CYP 1A) was downregulated. TP (2%) supplementation elicited a significant modulation in aforementioned indices; however, their levels did not attain that of the control values. Our findings concluded that LCH affects the O. niloticus immune response through the negative transcriptional influence on genes linked to immunity and induction of oxidative injury of the immune organs. Besides, dietary TP (2%) could be a proper candidate to modulate the compromised immunity in response to LCH exposure in O. niloticus aquaculture.

Protective effect of Spirulina platensis against physiological, ultrastructural and cell proliferation damage induced by furan in kidney and liver of rat.

The modulatory role of the Spirulina platensis (SP) against furan-induced (FU) hepatic and renal damage was assessed in this study. For achieving this, sixty rats were distributed into six groups: control group, SP-administered group (300 mg/kg b.wt orally for 28 days), a FU-intoxicated group (16 mg/kg b.wt, orally, daily for 28 days), protective co-treated group SP/F (administered SP 300 mg/kg b.wt, one week before, and concurrently with FU intoxication), therapeutic co-treated group FU/SP (administered SP 300 mg/kg b.wt, one week after FU intoxication for 28 days) and protective/therapeutic co-treated group SP/FU/SP (administered SP one week before and after, concurrently with FU intoxication). Subsequently, the biochemical responses and the histology of hepatic and renal tissues in treated rats were assessed. The results indicated that FU intoxication induced a significant hepato- and nephropathy represented by the elevation in the values of tissue injury biomarkers and reduction in protein levels. Histologically, a wide range of morphological, cytotoxic, inflammatory, and vascular alterations as well as downregulation in the immunoexpression of the proliferating cell nuclear antigen (PCNA) and the proliferation-associated nuclear antigen (Ki-67) were induced by FU intoxication. Oral SP administration, particularly in the protective/therapeutic co-treated group, markedly supressed the serum levels of the tissue injury biomarkers, diminished the inflammatory response, restored the cytotoxic alterations, upregulated the immunoexpression of PCNA and Ki-67, and restored the perturbed morphology of the hepatic and renal tissues. In conclusion, the obtained data demonstrated that SP co-administration elicits both protective and therapeutic potential against the FU-induced hepato- and nephropathy.

Restoring strategy of ethanolic extract of Moringa oleifera leaves against Tilmicosin-induced cardiac injury in rats: Targeting cell apoptosis-mediated pathways.

Tilmicosin (Til), an effective macrolide antibiotic, is widely used against respiratory diseases in livestock; however, its treatment is associated with cardiac tissue impairments. In this study, the ethanolic extract of Moringa oleifera (MO) leaves was investigated at two doses (400 and 800 mg/kg body weight [bw], orally) to determine its role in counteracting the effects of Til treatment (75 mg/kg bw) on the cardiac tissue in rats, exploring the oxidative stress-mediated damage and apoptosis. A high dose of MO ethanolic extract elicits considerable changes in the body weight, reduces the mortality rate, neutralizes the impaired cardiac injury markers, improves antioxidant endpoints (total antioxidant capacity, superoxide dismutase, catalase activity, and reduced glutathione level). Also it attenuates the oxidative stress indices (total reactive oxygen species, 8-hydroxy-2-deoxyguanosine, lipid peroxides [malondialdehyde], and protein carbonyl levels) that are associated with Til injection. The co-administration of MO ethanolic extract with Til considerably modulates the expression of apoptosis pathway-encoding genes (Bcl-2, caspase-3, Bax, p53, apoptosis-inducing factor, and Apaf-1), particularly in the high-dose group. Our results support that the concurrent administration of MO ethanolic extract with Til at a dose of 800 mg/kg bw increases the protective activity of the antioxidant system and delays or slows the pathological development of cardiotoxicity mediated by Til injection.

Transcriptomic profile change, immunological response and disease resistance of Oreochromis niloticus fed with conventional and Nano-Zinc oxide dietary supplements.

The present investigation was performed to evaluate the efficiency of Zinc oxide (ZnO) as a fish feed additive in immunomodulation of Oreochromis niloticus. Fish were fed on ZnO nano-particles (nZnO) and conventional (ZnO) in two concentrations (30 and 60 mg/kg diet), in addition to the control fish which was fed on Zn free diet. After 6° days, the highest survival rate was recorded in the nZnO30 -supplemented group. The total antioxidant capacity (TAC) and antioxidant enzymes were improved in different dietary Zn supplementation, obviously in the nZnO30 -supplemented group, while the lowest antioxidant status was noticed nZnO60 supplemented fish. The lipid peroxides (MDA) level was diminished upon Zn supplementation, particularly in nZnO30-supplemented group but showed a significant elevation in the nZnO60-supplemented group. Furthermore, the immune parameters examined, lysozyme activity, bactericidal activity, and IgM were significantly higher in ZnO60, and nZnO30 supplemented groups. The C-reactive protein (CRP) level showed no significant increase in response to Zn supplementation in the both forms at level of 30 mg/kg diet, but showed marked elevation in nZnO60- supplemented group. The mRNA expression profile of both interleukin 8 (IL-8), interleukin 1, beta (IL-1ß) encoding genes showed an up-regulation that was found in all Zn- supplemented groups, but more pronounced in nZnO60-supplemented group. On the other hand, the expression pattern of myxovirus resistance (Mx)-encoding gene showed no remarkable difference between the Zn- supplemented and control fish. The expression level of CXC-chemokine, toll-like receptor 7 (TLR-7), immunoglobulin M heavy chain (IgM heavy chain) and interferon gamma (IFN-γ) gene was upregulated in Zn-supplemented groups particularly in the nZnO30- supplemented group. While, the lowest expression was found in nZnO60- and ZnO30-supplemented groups. Here, Zn supplementation promoted the immune and antioxidant strength in fish mainly in nano form at the level of 30 mg/kg diet but not at 60 mg/kg diet that disrupt the immune and antioxidant status and promote inflammatory response.

Inflammatory and oxidative injury is induced in cardiac and pulmonary tissue following fipronil exposure in Japanese quail: mRNA expression of the genes encoding interleukin 6, nuclear factor kappa B, and tumor necrosis factor-alpha.

The phenylpyrazole insecticide, fipronil, isused for the eradication of insects in agriculture, which also exposes various non-target groups such as birds and animals. Our aim was to assess the cardiac and pulmonary consequences of sub-acute administration of fipronil (1∕5 LD50; 2.26 mg/kg) in the Japanese quail for fifteen days and to determine the tissue recovery over a period of 60 days. Fipronil exposure led to a significant decrease in the body weight of the treated birds. Its exposure also induced cardiac and pulmonary damage of varying degrees. Fipronil increased the lipid peroxide (LPO) and nitric oxide (NO) contents as well as indices of tissue injury in the serum of exposed birds. Furthermore, it decreased the antioxidant indices in both the organs. Most of these changes gradually reversed and the histological changes, particularly of the heart, reversed completely by day-60 of recovery. Furthermore, alterations in the mRNA gene expressions of Nuclear factor kappa B (NF-κB), Interleukin 6 (IL-6), and Tumor necrosis factor-alpha (TNF-α) were monitored by quantitative polymerase chain reaction (RT-PCR). In both the tissues, a significant up-regulation of the transcripts was recorded after fipronil administration, which was reversed during the recovery period in the heart tissue except for TNF-α, while the transcripts in the lung tissue declined non-significantly. This study showed that the exposure of Japanese quail to fipronil has a profound negative impact on heart and lung including oxidative injury and tissue inflammation. Fipronil can induce the activity of NF-κB inflammatory -signaling pathway that play a role in the associated tissue inflammation. Although most of the cardiac changes could be reversed after a recovery period of sixty days, the pulmonary changes did not reverse much.

Moringa oleifera extract attenuates the CoCl2 induced hypoxia of rat's brain: Expression pattern of HIF-1α, NF-kB, MAO and EPO.

Hypoxia-induced oxidative stress and apoptosis are the major hallmark explanations underlying brain dysfunction. Hypoxia in the current study was induced by Cobalt chloride (CoCl2) treatment in rats. The aim of this experiment was to explore the potential ameliorative potency of Moringa oleifera ethanolic extract (MO) against experimentally induced hypoxia on the structure and function of the rat's brain. Fifty male rats were allocated to five groups (10 rats each): a control group, a MO-treated group (400 mg/kg bw, orally), a CoCl2-treated group (40 mg/kg bw/day, orally), a prophylaxis group, and a therapeutic co-treated group. Oxidative stress biomarkers and monoamine neurotransmitter were evaluated in brain tissue. In addition, qRT-PCR for expression pattern of HIF-1α, EPO, CYTO, NF-kB, and MAO-A. Glial fibrillary acidic protein (GFAP), apoptotic markers (BCL-2 and caspase 3) were detected immunohistochemically in brain cells. The results revealed a significantly lower concentration of GABA, monoamine neurotransmitter in hypoxic rat's brain. Moreover, an evident up-regulation of the mRNA expression of HIF-1α, EPO, CYTO, NF-kB, and MAO-A. There was marked encephalopathy manifested by pyknotic neurons with eosinophilic cytoplasm, vacuolations and cerebral congestions in the hypoxic rat brains. Additionally, the score of neuronal expression occupied by GFAP- positive astroglia, Caspase-3 and microglial CD68 were elevated but Bcl-2 expression was found decreased in the hypoxic group than control. The endpoints of this study clearly stated that MO ethanolic extract suggestively counteracted neurotoxic impacts caused by hypoxia, particularly when it administered prior to and concurrently with CoCl2 administration.

Differential susceptibility of kidneys and livers to proliferative processes and transcriptional level of the genes encoding desmin, vimentin, connexin 43, and nestin in rats exposed to furan.

In this study, we aimed to assess the differential toxic impact, induced by furan exposure, on the liver and kidney tissues by estimating reactive oxygen species (ROS) level, total antioxidant capacity (TAC), oxidative damage, and the tissue injury markers in a male rat model. To explain such impacts, 20 rats were assigned into two groups: a control group, where rats were administered corn oil as a vehicle, and a furan-administered group, where furan was orally administered to rats at a dose of 16 mg/kg b wt/day (five days per week over eight weeks). The transcriptional levels of intermediate filament proteins (desmin, vimentin, nestin, and connexin 43) were assessed by using quantitative real-time polymerase chain reaction (PCR), and the cell proliferation markers (proliferating cell nuclear antigen [PCNA] and proliferation-associated nuclear antigen [Ki-67]) were recognized by immunohistochemical analysis. Furthermore, the ultrastructural changes of liver and kidney were monitored using electron microscopy. Our findings showed that furan exposure could induce hepatic and renal damage to different extents. Furan can increase the ROS content, oxidative damage indices, and liver tissue injury indices but not kidney injury indices. Furthermore, it decreases the TAC in the serum of exposed rats. In addition, furan exposure was associated with changes in the mRNA expression pattern of intermediate filament proteins in both kidney and liver tissues. Moreover, furan enhances the expression of PCNA and Ki-67 in the liver tissues but not in the kidney tissues. The ultrastructure evaluation revealed the incidence of glomerular podocyte degeneration and hepatocyte injury. These results conclusively demonstrate that the deleterious effects of furan are caused by promoting fibrosis and hepatocyte proliferation in liver tissues and triggering podocyte injury in the kidney tissues.