The immunosuppressive, growth-hindering, hepatotoxic, and oxidative stress and immune related-gene expressions-altering effects of gibberellic acid in Oreochromis niloticus: A mitigation trial using alpha-lipoic acid.

This study aimed to examine the effects of gibberellic acid (GBA) on growth, hemato-biochemical parameters related to liver functions, digestive enzymes, and immunological response in Oreochromis niloticus. Besides, the probable underlying mechanisms were explored by assessing antioxidant, apoptotic, and immune-related gene expression. Furthermore, the likelihood of restoration following alpha-lipoic acid (LIP) dietary supplementation was explored. The fish (average initial weight 30.75 ± 0.46) were equally classified into four groups: the control group, the LIP group (fed on a basal diet plus 600 mg/kg of LIP), the GBA group (exposed to 150 mg GBA/L), and the GBA + LIP group (exposed to 150 mg GBA/L and fed a diet containing LIP and GBA) for 60 days. The study findings showed that LIP supplementation significantly reduced GBA's harmful effects on survival rate, growth, feed intake, digestive enzymes, and antioxidant balance. Moreover, the GBA exposure significantly increased liver enzymes, stress markers, cholesterol, and triglyceride levels, all of which were effectively mitigated by the supplementation of LIP. Additionally, LIP addition to fish diets significantly minimized the histopathological alterations in the livers of GBA-treated fish, including fatty change, sharply clear cytoplasm with nuclear displacement to the cell periphery, single-cell necrosis, vascular congestion, and intralobular hemorrhages. The GBA-induced reduction in lysozyme activity, complement C3, and nitric oxide levels, together with the downregulation of antioxidant genes (cat and sod), was significantly restored by dietary LIP. Meanwhile, adding LIP to the GBA-exposed fish diets significantly corrected the aberrant expression of hsp70, caspase- 3, P53, pcna, tnf-a, and il-1ß in O. niloticus liver. Conclusively, dietary LIP supplementation could mitigate the harmful effects of GBA exposure on fish growth and performance, physiological conditions, innate immunity, antioxidant capability, inflammatory response, and cell apoptosis.

Using Azadirachta indica protein hydrolysate as a plant protein in Nile tilapia (Oreochromis niloticus) diet: Effects on the growth, economic efficiency, antioxidant-immune response and resistance to Streptococcus agalactiae.

A feeding trial for 90 days was conducted on Nile tilapia (Oreochromis niloticus) (average weight: 25.50 ± 0.05 g) to evaluate the effect of dietary inclusion of Azadirachta indica seed protein hydrolysate (AIPH). The evaluation included the impact on the growth metrics, economic efficiency, antioxidant potential, hemato-biochemical indices, immune response, and histological architectures. A total of 250 fish were randomly distributed in five treatments (n = 50) and received diets included with five levels of AIPH (%): 0 (control diet, AIPH0), 2 (AIPH2), 4 (AIPH4), 6 (AIPH6) or 8 (AIPH8), where AIPH partially replace fish meal by 0, 8.7%, 17.4%, 26.1%, and 34.8%, respectively. After the feeding trial, a pathogenic bacterium (Streptococcus agalactiae, 1.5 × 108 CFU/mL) was intraperitoneally injected into the fish and the survival rate was recorded. The results elucidated that AIPH-included diets significantly (p < 0.05) enhanced the growth indices (final body weight, total feed intake, total body weight gain, and specific growth rate) and intestinal morpho-metrics (villous width, length, muscular coat thickness, and goblet cells count) in comparison to the control diet, with the AIPH8 diet recording the highest values. Dietary AIPH inclusion significantly improved (p < 0.05) the economic efficacy indicated by reduced feed cost/kg gain and increased performance index. The fish fed on the AIPH diets had noticeably significantly higher (p < 0.05) protein profile variables (total proteins and globulin) and antioxidant capabilities (superoxide dismutase and total antioxidant capacity) than the AIPH0 group. The dietary inclusion of AIPH significantly (p < 0.05) boosted the haematological parameters (haemoglobin, packed cell volume %, and counts of red blood cells and white blood cells) and immune indices (serum bactericidal activity %, antiprotease activity, and immunoglobulin M level) in a concentration-dependent manner. The blood glucose and malondialdehyde levels were significantly (p < 0.05) lowered by dietary AIPH (2%-8%). The albumin level and hepatorenal functioning parameters (aspartate aminotransferase, alanine aminotransferase, and creatinine) were not significantly (p > 0.05) altered by AIPH diets. Additionally, AIPH diets did not adversely alter the histology of the hepatic, renal or splenic tissues with moderately activated melano-macrophage centres. The mortality rate among S. agalactiae-infected fish declined as dietary AIPH levels rose, where the highest survival rate (86.67%) was found in the AIPH8 group (p < 0.05). Based on the broken line regression model, our study suggests using dietary AIPH at the optimal level of 6%. Overall, dietary AIPH inclusion enhanced the growth rate, economic efficiency, health status, and resistance of Nile tilapia to the S. agalactiae challenge. These beneficial impacts can help the aquaculture sector to be more sustainable.

The palliative effect of mulberry leaf and olive leaf ethanolic extracts on hepatic CYP2E1 and caspase-3 immunoexpression and oxidative damage induced by paracetamol in male rats.

This study investigated the possible protective role of mulberry leaf (MLE) and olive leaf (OLE) ethanolic extracts against paracetamol (PTL)-induced liver injury in rats compared to silymarin as a reference drug. Initially, MLE and OLE were characterized using gas chromatography-mass spectrometry (GC/MS). Then, forty male Sprague Dawley rats were divided into five groups: the negative control group orally received distilled water for 35 days, the PTL-treated group (PTG) received 500 mg PTL/kg b. wt. for 7 days, the MLE-treated group (MLTG) received 400 mg MLE/kg b. wt., the OLE-treated group (OLTG) received 400 mg OLE/kg b. wt., and the silymarin-treated group (STG) received 100 mg silymarin/kg b. wt. The last three groups received the treatment for 28 days, then PTL for 7 days. The GC-MS characterization revealed that MLE comprised 19 constituents dominated by ethyl linoleate, phytol, hexadecanoic acid, ethyl ester, and squalene. Moreover, OLE comprised 30 components, and the major components were 11-eicosenoic acid, oleic acid, phytol, and à-tetralone. MLE and OLE significantly corrected the PTL-induced normocytic normochromic anemia, leukocytosis, hypercholesterolemia, and hypoproteinemia. Moreover, the MLE and OLE pretreatment considerably suppressed the PTL-induced increment in serum levels of hepatic enzymes, including alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase. Furthermore, the PTL-induced depletion in antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, and catalase, and the rise in hepatic malondialdehyde content were significantly reversed by the MLE and OLE pretreatment. Besides, MLE and OLE pretreatment significantly protected the hepatic tissue against PTL-induced DNA damage, pathological perturbations, and increased caspase 3 and CYP2E1 immunoexpression. Of note, OLTG showed better enhancement of most indices rather than MLTG. Conclusively, these findings imply that OLE, with its antioxidant and antiapoptotic capabilities, is superior to MLE in protecting against PTL-induced liver injury.

Chitosan-Ocimum basilicum nanocomposite as a dietary additive in Oreochromis niloticus: Effects on immune-antioxidant response, head kidney gene expression, intestinal architecture, and growth.

Several studies have looked into the use of basil, Ocimum basilicum (L.) in aquaculture as a dietary additive; however, more research is needed to see the possibility of it's including in nanocarriers in aquafeeds. An experiment was undertaken to highlight the efficacy chitosan-Ocimum basilicum nanocomposite (COBN), for the first time, on Nile tilapia (Oreochromis niloticus) growth, stress and antioxidant status, immune-related parameters, and gene expression. For 60 days, fish (average weight: 23.55 ± 0.08 g) were fed diets provided with different concentrations of COBN (g/kg): 0 g [COBN0], 1 g [COBN1], 2 g [COBN2], and 3 g [COBN3], where COBN0 was kept as control diet. Following the trial, the fish were challenged with pathogenic bacteria (Aeromonas sobria) and yeast (Candida albicans) infection. In comparison to the control (COBN0), a notable increase in growth parameters (weight gain, feed intake, and specific growth rate) and intestinal morphometric indices (average intestinal goblet cells count, villous width, and length) in all COBN groups was observed, where COBN2 and COBN3 groups had the highest values. The COBN diets significantly (p < 0.05) declined levels of serum triglycerides, glucose, cholesterol, and hepatic malondialdehyde. Moreover, the higher levels of serum biochemical biomarkers (growth hormone, total protein, globulin, and albumin), immunological parameters (phagocytic activity%, nitric oxide, and lysozyme), and hepatic antioxidant parameters (superoxide dismutase, total antioxidant capacity, and glutathione peroxidase) were obvious in the COBN2 and COBN3 groups followed by COBN1. The immune-antioxidant genes (TNF-α, IL-10, IL-1ß, TGF-ß, GPx, and SOD) were found to be considerably up-regulated in all COBN groups (COBN2 and COBN3 followed by COBN1). Fifteen days post-challenge with A. sobria and C. albicans, the highest survival rate was recorded in the COBN2 group (83.33 and 91.67%) followed by the COBN3 group (75 and 83.33%), respectively. The findings showed that a dietary intervention with COBN can promote growth, intestinal architecture, immunity, and antioxidant markers as well as protect O. niloticus against A. sobria and C. albicans infection. As a result, the COBN at a dose of 2 g/kg could be used as a food additive for the sustainable aquaculture industry.

Boldenone Undecylenate-Mediated Hepatorenal Impairment by Oxidative Damage and Dysregulation of Heat Shock Protein 90 and Androgen Receptors Expressions: Vitamin C Preventive Role.

Boldenone Undecylenate (BLD) is a synthetic derivative of testosterone and a widely used anabolic androgenic steroid. The health risk of BLD use as a pharmaceutical or dietary supplement is still underestimated and under-reported. Vitamin C (VC) has been recognized as an antioxidant with prominent hepatorenal protective effects. This study investigated the possible preventive activity of VC against BLD-induced hepatorenal damage. Forty adult male Wistar rats were classified into five groups: control, vehicle control, VC (orally given 120 mg/kg b. wt./day), BLD (intramuscularly injected 5 mg/kg b. wt./week), and BLD + VC-treated groups. The experiment continued for eight weeks. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. Serum contents of total protein (TP), albumin (ALB), globulin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and very-low-density lipoprotein-cholesterol (VLDL-C) were also assayed. Urea, creatinine, and uric acid levels were determined together with sodium and potassium electrolytes measuring. Moreover, oxidative stress indicators including reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GSR) as well as malondialdehyde (MDA) levels were measured in both hepatic and renal tissues. Corresponding histological examination of renal and hepatic tissues was conducted. Besides, immunohistochemical evaluations for androgen receptors protein (AR) and heat shock protein 90 (Hsp 90) expressions were performed. BLD caused significant rises in serum ALT, AST, TP, ALB, TC, TG, LDL-C, VLDL-C, urea, creatinine, uric acid, potassium, and MDA levels. Further, BLD-injected rats showed significant declines in the serum levels of HDL-C, sodium, GSH, GPx, GST, and GSR. Besides, distinct histopathological perturbations were detected in renal and hepatic tissues of BLD-injected rats. AR and Hsp 90 immunoexpression were increased in hepatic and renal tissues. In contrast, VC significantly reversed the BLD-induced hepatorenal damage in co-treated rats but not ameliorated AR protein overexpression. VC could be an efficient preventive supplement for mitigating BLD-induced hepatorenal damage, possibly via controlling oxidative stress events.

Adsorptivity of mercury on magnetite nano-particles and their influences on growth, economical, hemato-biochemical, histological parameters and bioaccumulation in Nile tilapia (Oreochromis niloticus).

Among toxic pollutants, Mercury (Hg) is a toxic heavy metal that induces harmful impacts on aquatic ecosystems directly and human being's health indirectly. This study confirmed the in vitro magnetic potential of magnetite Nano-Particles (Fe3O4 NPs) against waterborne Hg exposure-induced toxicity in Nile tilapia (Oreochromis niloticus). We further evaluate the safety profile of Fe3O4 NPs on fish growth, hemato-biochemical, histological parameters, bioaccumulation in muscles, and economy. Magnetite nanoparticles were characterized, adsorption loading to Hg ions was investigated, and testing different concentrations of Fe3O4 NPs (0.2, 0.4, 0.6, 0.8, and 1.0 mg/L) was applied to determine the highest concentration of adsorption. An in vivo experiment includes 120 fish with an average weight of 26.2 ± 0.26 g were randomly divided into 4 equal groups, each group had three replicates (n = 30 fish/group; 10 fish/ replicate). All groups were fed on a reference basal diet and the experiment was conducted for 30 days. The first group (G1) was allocated as a control. The second group (G2) received 1.0 mg/L aqueous suspension of Fe3O4 NPs. The third group (G3) was exposed to an aqueous solution of Hg ions at a concentration of 0.025 mg/L. Meanwhile, the fourth group (G4) acquired an aqueous suspension composed of a mixture of Hg ions and Fe3O4 NPs as previously mentioned. Throughout the exposure period, the clinical signs, symptoms, and mortalities were recorded. The Hg ions-exposed group induced the following consequences; reduced appetite resulting in reduced growth and less economic efficiency; microcytic hypochromic anemia, leukocytosis, lymphopenia, and neutrophilia; sharp and clear depletion in the immune indicators including lysozymes activity, immunoglobulin M (IgM), and Myeloperoxidase activities (MPO); significant higher levels of ALT, AST, urea, creatinine, and Superoxide dismutase (SOD); histological alterations of gill, hepatic and muscular tissues with strong expression of apoptotic marker (caspase 3); and a higher accumulation of Hg ions in the muscles. Surprisingly, Fe3O4 NPs-supplemented groups exhibited strong adsorption capacity against the Hg ions and mostly removed the Hg ions accumulation in the muscles. Also, the hematological, biochemical, and histological parameters were recovered. Thus, in order to assess the antitoxic role of Fe3O4 NPs against Hg and their safety on O. niloticus, and fill the gap of the research, the current context was investigated to evaluate the promising role of Fe3O4 NPs to prevent Hg-exposure-induced toxicity and protection of fish health, which ascertains essentiality for sustainable development of nanotechnology in the aquatic environment.

Di(2-ethylhexyl) adipate plasticizer triggers hepatic, brain, and cardiac injury in rats: Mitigating effect of Peganum harmala oil.

Di(2-ethylhexyl) adipate (DEHA) is a widely used plasticizer and prevalent environmental contaminant. In this study, DEHA concentrations in the milk, cheese, and butter samples wrapped with food-grade commercial polyethylene films and stored at 4 °C for 30 days were detected using gas chromatographic analysis. Also, the effects of exposure to a high dose of DEHA for a long duration on the liver, brain, and heart of Wistar rats were assessed. Besides, the possible beneficial effect of Peganum harmala oil (PGO), in relieving DEHA induced adverse effects was explored. For this purpose, four groups (8 rats/group) were orally given physiological saline, PGO (320 mg/kg bwt), DEHA (2000 mg/kg bwt), or PGO + DEHA for 60 days. The results revealed that the DEHA concentrations in the tested dairy products were ordered as follows: (butter > cheese > milk). Notably, the detected levels in butter were higher than the specific migration limit in foods. DEHA induced a significant increase in the serum levels of glucose, alanine transaminase, aspartate transaminase, acetylcholine esterase, creatine kinase-myocardium bound, malondialdehyde, tumor necrosis factor-α, and interleukin-1ß. But, significant hypoproteinemia, hypoalbuminemia, hypoglobulinemia, and hypocholesterolemia were evident following DEHA exposure. A significant reduction in the serum level of superoxide dismutase, reduced glutathione, and brain-derived neurotrophic factor was recorded. Besides, a significant downregulation in hepatic CYP2E1, brain glial fibrillary acidic protein, and cardiac troponin I gene expression was noticed. Moreover, DEHA exposure induced a significant decrease in Bcl-2 immunolabeling, but Caspase-3 immunoexpression was increased. On the contrary, PGO significantly recused DEHA injurious impacts. Therefore, PGO could represent a promising agent for preventing DEHA-induced hepatotoxicity, neurotoxicity, and cardiotoxicity.

The protective efficacy of vitamin E and cod liver oil against cisplatin-induced acute kidney injury in rats.

Cisplatin (CP) is a highly effective chemotherapeutic agent against neoplasms, but its clinical utility is limited due to the side effects of its dose-dependent nephrotoxicity. Vitamin E (Vit E) and cod liver oil (CLO) are natural substances with chemoprotective effects. The present study was conducted to evaluate the protective effects of Vit E and/or CLO for CP-induced acute kidney injury (AKI) in rats. This study involved 40 mature male Wistar albino rats that were equally allocated into eight groups: Veh, Vit E, CLO, Vit E + CLO, CP, Vit E + CP, CLO + CP, and Vit E + CLO + CP. The co-administration of Vit E and CLO significantly ameliorated CP-induced elevations in serum creatinine (Cr), blood urea nitrogen (BUN), interleukin 1 beta (IL-1ß), and interleukin- 6 (IL-6). Further, rats that received Vit E and/or CLO showed significant decrease in malondialdehyde (MDA) and increases in superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels in renal tissues, compared to CP-intoxicated rats. Additionally, the treatment restored the normal histological architecture (except for few cast formations) and upregulated the immunostaining area% of aquaporin 3 (AQP3) and downregulated the immunostaining area% of Bcl2 associated X protein (BAX) and inducible nitric oxide synthase (iNOS). The observed effects were stronger in the combination treatment group. The obtained data revealed that Vit E and CLO co-administration protects against the CP-induced AKI more than monotherapy with Vit E or CLO.

Saussurea lappa Ethanolic Extract Attenuates Triamcinolone Acetonide-Induced Pulmonary and Splenic Tissue Damage in Rats via Modulation of Oxidative Stress, Inflammation, and Apoptosis.

Background: In this era, worldwide interest has been directed towards using natural antioxidants to guard against drug side effects. Saussurea lappa is a famous medicinal plant with many biologically active compounds. Triamcinolone acetonide (TA) is an extensively used glucocorticoid. Hence, this study explored, for the first time, the possible beneficial effects of S. lappa ethanolic extract on TA-induced oxidative damage in the lung and spleen of rats. Methods: Five experimental groups were used: control group, S. lappa-treated group (600 mg/kg/day, orally), TA-treated group (40 mg/kg/twice/week I/P), S. lappa + TA co-treated group, and S. lappa/TA prophylactic group. Results: TA exposure significantly induced leukocytosis and neutrophilia. In addition, TA significantly reduced the levels of C-reactive protein, interleukin-12, tumor necrosis factor α, and immunoglobulins. Lung Caspase-3 overexpression and splenic CD8+ downregulation were also noted in the TA group. TA treatment significantly increased malondialdehyde concentration but reduced superoxide dismutase and glutathione peroxidase activities. S. lappa counteracted the TA oxidative and apoptotic effects. The best results were recorded in the prophylactic group. Conclusions: S. lappa has a remarkable protective effect via its anti-inflammatory, anti-apoptotic, and antioxidant capacity. Thus, it could be a candidate as a natural antioxidant to face glucocorticoid's harmful side effects.

The palliative role of Eruca sativa leaves dietary supplementation against oxidative stress, immunosuppression, and growth retardation in temperature-stressed Oreochromis niloticus.

This study was conducted to investigate the effects of dietary dried Rocket Leaves meal (DRLM) supplementation on growth performance, immune response, and antioxidant capacity of Oreochromis niloticus reared under different water temperature. For this purpose, five hundred and forty apparently healthy O. niloticus were allocated into nine groups fed three DRLM-supplemented diets (0,1, and 3%) and reared at three water temperature (18, 24, and 32°C) in a 3 × 3 total randomized factorial design. The results revealed that exposure of fish to low (18°C) or high (32°C) temperatures for 30 days evoked significant growth retardation, depleted antioxidant enzymes activities (Catalase; CAT and super oxide dismutase; SOD), lipid peroxidation (malondialdehyde; MDA), immunosuppression, altered cortisol level compared to those reared at 24°C. Moreover, a marked down-regulation of oxidative stress related genes with up-regulation of interleukin 1ß gene were apparent. In contrast, DRLM incorporation, particularly at 3%, in heat or cold stressed fish diets significantly enhanced growth, restored IgM and lysozymes levels, and SOD and CAT activities. Also, both the MDA and cortisol levels were significantly depressed. Furthermore, both antioxidant and immune-related genes expression were significantly corrected. Conclusively, 3% DRLM dietary supplementation in tilapia diet could be a promising strategy to alleviate the temperature stress-induced negative impacts on fish health and performance.