Total Glutathione Research Articles

Effect of pycnogenol on ischemia/reperfusion-induced oxidative and inflammatory damage in the ovaries of rats

Purpose: To investigate the protective effect of pycnogenol (PYC) against ischemia/reperfusion (I/R) ovarian damage induced by experimental ovarian torsion in rats using biochemical and histopathological methods.
 Methods: Four groups of rats (n = 6) were randomly assigned and designated as follows – SG: sham group, PCG: pycnogenol (40 mg/kg) group, IRG: ovarian ischemia-reperfusion group, and PIR: pycnogenol (40 mg/kg) + ovarian ischemia-reperfusion group. In IRG and PYC treatment groups, ischemia was induced in the right ovary for two hours with vascular clips. The ovary was reperfused for two hours after ischemia was induced. Then, the levels of malondialdehyde (MDA), total glutathione (tGSH), nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) in the ovarian tissues of rats were examined. Ovarian tissues were also examined histopathologically and follicle counts were performed.
 Results: Histopathological examination revealed that the developing follicles in ovary of I/R-induced group showed both morphological and cellular degeneration and vascular pathology. The PYC treatment group showed less ovarian damage, edema and vascular pathology than I/R-induced group (p < 0.05). The MDA, NF-κB, TNF-α and IL-1β levels in I/R-induced group were significantly higher than in SG and tGSH levels were significantly reduced by I/R damage (p < 0.05). Pycnogenol treatment reversed these biochemical indices as well as I/R-induced histopathological changes.
 Conclusion: Pycnogenol has a protective effect in rat ovaries by alleviating I/R-induced changes in biochemical parameters and histological disruptions. Further studies, including those in humans, to determine the effect of PYC on ovarian injuries would be required.

Sanguinarine chloride induces ferroptosis by regulating ROS/BACH1/HMOX1 signaling pathway in prostate cancer

BackgroundSanguinarine chloride (S.C) is a benzophenanthrine alkaloid derived from the root of sanguinaria canadensis and other poppy-fumaria species. Studies have reported that S.C exhibits antioxidant, anti-inflammatory, proapoptotic, and growth inhibitory effects, which contribute to its anti-cancer properties. Recent studies suggested that the antitumor effect of S.C through inducing ferroptosis in some cancers. Nevertheless, the precise mechanism underlying the regulation of ferroptosis by S.C remains poorly understood.MethodsA small molecule library was constructed based on FDA and CFDA approved small molecular drugs. CCK-8 assay was applied to evaluate the effects of the small molecule compound on tumor cell viability. Prostate cancer cells were treated with S.C and then the cell viability and migration ability were assessed using CCK8, colony formation and wound healing assay. Reactive oxygen species (ROS) and iron accumulation were quantified through flow cytometry analysis. The levels of malondialdehyde (MDA) and total glutathione (GSH) were measured using commercially available kits. RNA-seq analysis was performed to identify differentially expressed genes (DEGs) among the treatment groups. Western blotting and qPCR were utilized to investigate the expression of relevant proteins and genes. In vivo experiments employed a xenograft mice model to evaluate the anti-cancer efficacy of S.C.ResultsOur study demonstrated that S.C effectively inhibited the viability of various prostate cancer cells. Notably, S.C exhibited the ability to enhance the cytotoxicity of docetaxel in DU145 cells. We found that S.C-induced cell death partially relied on the induction of ferroptosis, which was mediated through up-regulation of HMOX1 protein. Additionally, our investigation revealed that S.C treatment decreased the stability of BACH1 protein, which contributed to HMOX1expression. We further identified that S.C-induced ROS caused BACH1 instability by suppressing USP47expression. Moreover, In DU145 xenograft model, we found S.C significantly inhibited prostate cancer growth, highlighting its potential as a therapeutic strategy. Collectively, these findings provide evidence that S.C could induce regulated cell death (RCD) in prostate cancer cells and effectively inhibit tumor growth via triggering ferroptosis. This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting ROS/USP47/BACH1/HMOX1 axis.ConclusionThis study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting the ROS/USP47/BACH1/HMOX1 axis. These findings offer novel insights into the underlying mechanism by which S.C inhibits the progression of prostate cancer. Furthermore, leveraging the potential of S.C in targeting ferroptosis may present a new therapeutic opportunity for prostate cancer. This study found that S.C induces ferroptosis by targeting the ROS/USP47/BACH1/HMOX1 axis in prostate cancer cells.Graphical

Comparison of the oxidative stress status of children with ITP in two therapies using methylprednisolone and methylprednisolone along with IVIG

Background: Idiopathic thrombocytopenic purpura (ITP) is a rare and autoimmune disorder determined by an abnormal reduction in the number of platelets. The current study aims to evaluate the oxidative stress status of children with ITP in two treatment methods using methylprednisolone and methylprednisolone with intravenous immunoglobulin (IVIG).
 Materials and Methods: This retrospective study was conducted on 60 children with ITP who referred to Baghaei Hospital in Ahvaz in 2021. All the ITP children were equally divided into two groups, 30 receiving methylprednisolone and 30 receiving methylprednisolone and IVIG. The sampling of the patients’ blood was done in two stages before and after the start of treatment. Then, malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant status (TAS), total oxidative status (TOS), catalase (CAT) and glutathione were measured according to the instructions in the commercial kit. The analyses were performed using SPSS software version 23. P value < 0.05 was significant.
 Results: The number of platelets after treatment in methylprednisolone and methylprednisolone+ IVIG groups was 133.44 ± 18.93 and 158.76 ± 34.76 (×103/µL), respectively. Itas significantly increased compared to that before the treatment (P = 0.04). The amount of TAC in the group receiving methylprednisolone + IVIG and the methylprednisolone group was 1.64 ± 0.18 and 1.26 ± 0.53 nm, respectively; there was a remarkable difference between the two groups (P = 0.001). Also, SOD, CAT and glutathione in the methylprednisolone + IVIG group were remarkably higher than those in the methylprednisolone group (P < 0.05). Finally, the levels of TOS were lower in the methylprednisolone + IVIG group (19.74 ± 9.93 μmol) than in the methylprednisolone group (26.65 ± 10.64 μmol) (P = 0.01).
 Conclusion: A combination of IVIG and methylprednisolone was found to have a greater effect on improving antioxidant status and decreasing the oxidative stress indices of ITP children.

Effects of puerarin as a feed additive on the laying performance, egg quality, endocrine hormones, antioxidant capacity, and intestinal morphology of aged laying hens

The aim of this study was to investigate the effects of puerarin (Pue), a phytoestrogen, on the production performance, egg quality, endocrine hormones, antioxidant capacity, and intestinal morphology in aged laying hens. A total of 180 Hy-Line Brown hens aged 480 d were randomly divided into 4 groups (n = 45 per group) and fed 0, 200, 400, and 800 mg/kg of Pue (Con, L-Pue, M-Pue, and H-Pue, respectively) during a 42-d experiment. Compared with the Con treatment, supplementation with H-Pue improved laying performance and egg quality by significantly increasing egg production, average egg weight, albumen height, yolk weight, and Haugh unit (P < 0.05) while decreasing the feed conversion ratio (P < 0.05). A diet supplemented with H-Pue significantly decreasing serum total triglycerides, total cholesterol, and low-density lipoprotein cholesterol, alanine aminotransferase (P < 0.05), and significantly increasing serum levels of follicle-stimulating hormone, luteinizing hormone and progesterone (P < 0.05). Antioxidant activity was improved by significantly increasing the activity of total antioxidant capacity, glutathione peroxidase and catalase but decreasing malondialdehyde levels in serum, jejunum, and ileum (P < 0.05), and superoxide dismutase activity exhibited a significantly increase in the jejunum and ileum (P < 0.05). Villus height and the ratio of villus height to crypt depth (P < 0.05) were significantly increased in the jejunum and ileum. In the jejunal and ileal mucosa, the three treatment groups increased the mRNA expression levels of Claudin-1 and Claudin-2 compared with Con (P < 0.05), and no significant effect was observed on the expression of Occludin and ZO-1. The results showed that dietary supplementation with Pue could improve the laying performance, egg quality, antioxidant capacity, hormonal profile, and intestinal morphology of aged laying hens.

Alkaloidal Extracts from Avicennia africana P. Beauv. (Avicenniaceae) Leaf: An Antiplasmodial, Antioxidant, and Erythrocyte Viable.

The emergence of drug-resistant parasites impedes disease management and eradication efforts. Hence, a reinvigorated attempt to search for potent lead compounds in the mangroves is imperative. This study evaluates in vitro antiplasmodial activity, antioxidant properties, and cytotoxicity of A. africana leaf alkaloidal extracts. The A. africana leaves were macerated with 70% ethanol to obtain a total crude extract. Dichloromethane and chloroform-isopropanol (3 : 1, v/v) were used to extract the crude alkaloids and quaternary alkaloids from the total crude. The antiplasmodial activities of the alkaloidal extracts were performed against 3D7 P. falciparum chloroquine-sensitive clone via the SYBR Green I fluorescence assay with artesunate serving as the reference drug. The alkaloidal extracts were further evaluated for antioxidant properties via the total antioxidant capacity (TAC), the total glutathione concentration (GSH), the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, and the ferric-reducing antioxidant power (FRAP) methods. The cytotoxic activity of the alkaloidal extracts was tested on erythrocytes using a 3-(4,5-dimethylthiazol-2-yl)-5-diphenyltetrazolium bromide-MTT assay with little modification. The phytocompounds in the alkaloidal extracts were identified via gas chromatography-mass spectrometry (GC-MS) techniques. The total crude extract showed good antiplasmodial activity (IC50 = 11.890 µg/mL). The crude and quaternary alkaloidal extracts demonstrated promising antiplasmodial effects with IC50 values of 6.217 and 6.285 µg/mL, respectively. The total crude and alkaloidal extracts showed good antioxidant properties with negligible cytotoxicity on erythrocytes with good selectivity indices. The GC-MS spectral analysis of crude alkaloidal extracts gave indole and isoquinoline alkaloids and several other compounds. Dexrazoxane was found to be the main compound predicted, with an 86% peak area in the quaternary alkaloidal extract. The crude and quaternary alkaloidal extracts exhibited antiplasmodial activities and ability to inhibit oxidative stress with negligible toxicity on erythrocytes. This may be good characteristics to avoid oxidative stress related to Plasmodium infection in the treatment of malaria.

Effects of benidipine, paracetamol, and their combination on postoperative and normal tissue pain thresholds.

Introduction: In clinical practice, inadequate pain inhibition leads to increased morbidity and mortality. Increased intracellular calcium, oxidants, and proinflammatory cytokines are known to play a role in the pathogenesis of postoperative pain. Therefore, we investigated the analgesic effects of benidipine, paracetamol, and benidipine-paracetamol combination (BPC) on postoperative and normal pain thresholds in rats. Material and methods: Sixty-four male albino Wistar rats weighing 285-295g were used. The without-incision rats were divided into 4 subgroups: healthy control, benidipine alone, paracetamol alone, and BPC. The scalpel-incision rats were divided into 4 subgroups: scalpel incision, scalpel incision + benidipine, scalpel incision + paracetamol, and scalpel incision + BPC. Paw pain thresholds of rats were measured using a Basile algesimeter. Biochemical analyses were performed on the paw tissues of 6 rats randomly taken from the experimental groups, each containing 8 rats. Rats were sacrificed immediately after the measurements. After the pain threshold tests were finished, the paw tissues were removed and malondialdehyde (MDA), total glutathione (tGSH), cyclooxygenase (COX), and interleukin-6 (IL-6) levels were measured. Results: There was no significant difference between the groups in paw pain threshold and measured biochemical parameters in rats without incision. The decrease in the pain threshold of the incised paw was also best prevented by BPC, followed by benidipine and then paracetamol. Furthermore, increases in scalpel-incised paw tissue MDA, COX-2, and IL-6 levels and the decrease in tGSH were significantly suppressed by benidipine and BPC, while paracetamol could only significantly inhibit the increase in IL-6 production. Conclusion: The combination of the L-type Ca2+ channel blocker benidipine and paracetamol (BPC) may provide potent analgesia. Our experimental results support that BPC may be useful in the treatment of severe pain that cannot be adequately inhibited by paracetamol.

Regulatory network of ferroptosis and autophagy by targeting oxidative stress defense using sulfasalazine in triple-negative breast cancer

AimsThe cellular defense system against oxidative stress is important for the survival ability and sensitization in chemotherapy; however, the regulatory mechanisms remain unknown in triple-negative breast cancer (TNBC) cells. This study aimed to investigate the relationship between ferroptosis and autophagy by targeting the defense of oxidative stress through the cystine transporter (xCT) using sulfasalazine (SASP), which is a widely employed xCT inhibitor. Main methodsWe analyzed the cell death process of SASP in human TNBC cells, and examined the effects of SASP on tumor progression by using xenograft mouse model. Key findingsTNBC cells demonstrated a high defense capacity against reactive oxidative species through xCT. SASP significantly attenuated oxidative stress resistance in MDA-MB-231, which is a generally used model cell as TNBC, through decreased glutathione levels, causing a marked iron-dependent ferroptotic cell death induction. Moreover, autophagy was required to trigger efficient SASP-induced ferroptosis at the early stage of cell death. Tamoxifen, which is currently in clinical use as the gold standard for endocrine therapy of estrogen receptor-positive breast cancer, was a beneficial tool as an autophagy regulator under ferroptotic cell death by SASP. Additionally, SASP suppressed tumor growth and metastasis progression through total glutathione reduction in the primary tumor, indicating high anticancer activity against TNBC without liver injury in vivo. SignificanceWe revealed that SASP can efficiently induce ferroptosis associated with autophagy and that an understanding of the mechanism of cell death regulation by SASP is a promising new strategy for TNBC therapy and drug repositioning.

The role of mitochondrial bioenergy and system glutathione in deficiency of Coenzyme Q and Complex I

Cytokine Coenzyme Q10 (CoQ10) is an insoluble coenzyme that is a component of the electron transport chain and is involved in oxidative phosphorylation in mitochondria. By a decrease in CoQ10, the energy requirements of the cell are not fully covered: cell division slows down, and the processes of tissue renewal and regeneration are disrupted. In our work, we used a model of mice CoQ9 Knockin (R239X). In homozygous mutant mice, a strong decrease in CoQ7 protein and the accumulation of dimethoxyubiquinone are observed. An impairment of hydrogen sulfide metabolism was previously identified as a significant pathomechanism of primary Coenzyme Q deficiency. The experimental results showed that the disruption of sulfide and glutathione metabolism in Coq9R239X mice is directly dependent on CoQ levels. Therefore, changes in dietary sulfur-containing amino acids do not alter sulfide metabolism and the glutathione system in Coq9R239X mice. As our experiments have shown, an increase in total glutathione is observed only in symptomatic brain tissue. It can be assumed that this is due to oxidative stress in the symptomatic brain tissue, which is often found with mitochondrial dysfunction.

Protective Effect of Ramipril Against Oxidant and Proinflammatory Cytokine Damage Induced by Ischemia-Reperfusion in Ovarian Tissue in Rats

It is known that the increase in oxidants and proinflammatory cytokines, as well as the decrease in antioxidants, play a role in ovarian ischemia-reperfusion (I/R) injury. The antioxidant and anti-inflammatory properties of ramipril have been studied in various diseases. This study aims to investigate the effect of ramipril on I/R-induced ovarian damage in rats. Rats were divided into healthy (HG), sham (SG), ovary I/R (OIR), and ramipril + ovary I/R (ROIR) groups (n = 6/each group). One hour before the surgical procedures, ROIR was given 2 mg/kg ramipril. The lower abdomen of the SG, OIR, and ROIR was surgically opened. Right ovarian tissues of OIR and ROIR were subjected to 2 hours of ischemia and 6 hours of reperfusion. Then, all animals were euthanized, and their right ovaries were removed. Ovarian tissues were examined for oxidants (malondialdehyde), antioxidants (total glutathione, superoxide dismutase, and catalase), and proinflammatory cytokines (nuclear factor kappa-B, tumor necrosis factor-alpha, interleukin 1 beta, and interleukin-6) analysis was performed. Tissues were examined histopathologically. The ovarian tissue of the OIR, which underwent the I/R procedure, exhibited a significant increase in oxidant and proinflammatory cytokine levels, along with a decrease in antioxidant levels (P < .001). Ramipril suppressed the I/R-induced increase in oxidants and pro-inflammatory cytokines and the decrease in antioxidants (P < .001). Ramipril also attenuated I/R-induced histopathological damage in ovarian tissue (P < .05). Ramipril treatment may be a treatment strategy to protect ovarian tissue against oxidative and inflammatory damage of I/R.

Effect of Dietary Puerarin Supplementation on Growth Performance, Immune Response, Antioxidant Capacity, and Intestinal Morphology in Domestic Pigeons (Columba livia).

Puerarin is an isoflavone extracted from Gegen (Pueraria lobata) and has been widely utilized to treat various human diseases; however, information regarding its benefits in animal production is limited. In this study, we aimed to investigate the influence of dietary puerarin supplementation on growth performance, immune organ index, immunoglobulin profile, antioxidant capacity, and intestinal morphology in pigeons. In total, 375 healthy 28-day-old White King pigeons were randomly divided into five groups, each consisting of five replicates and 15 pigeons per replicate. Each group was administered one of five dietary treatments: the basal diet, or the basal diet supplemented with 40, 80, 120, or 160 mg/kg puerarin. Treatment duration was 30 days following a 7-day acclimation period. Puerarin treatment did not significantly alter the growth performance of pigeons but afforded a significant linear enhancement in the thymus index (P < 0.05). Additionally, puerarin supplementation significantly increased serum immunoglobulin A and immunoglobulin M levels in pigeons in a linear manner (P < 0.05). Similarly, puerarin significantly and linearly increased the activities of total antioxidant capacity, superoxide dismutase, glutathione, and catalase in the serum and liver, and decreased the malondialdehyde content (P < 0.05). Moreover, the villus height (VH), crypt depth (CD), and VH/CD ratio of the small intestine (including the duodenum, jejunum, and ileum) increased linearly upon puerarin supplementation (P < 0.05). Collectively, these results indicate that puerarin supplementation could improve the immune response, antioxidant capacity, and intestinal morphology of pigeons.

Regulation of colon injury and improvement of exercise performance in exhausted running mice by Lactobacillus pentosus CQZC02.

In this study, strenuous forced exercise caused intestinal damage and reduced the exercise capacity of mice. However, the antioxidant and anti-inflammatory properties of Lactobacillus pentosus CQZC02 (LPCQZC02) were found to improve both the intestinal barrier and exercise function in mice. The effectiveness of LPCQZC02 was confirmed through various methods, including kit detection, pathological observation, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and intestinal flora analysis. The findings demonstrated that LPCQZC02 could control colonic index, lessen colonic enlargement caused by intense exercise, and extend the running duration of mice. Serum levels of total superoxide dismutase (T-SOD), glutathione (GSH), and interleukin-10 (IL-10) were elevated, whereas those of malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were reduced. The findings of the mRNA expression analysis revealed that in the colons of mice who remarkably exercised, LPCQZC02 could increase the expression levels of zonula occludens-1 (ZO-1), occludin-1, and claudin-1 genes. Additionally, in skeletal muscle tissue, it could downregulate TNF-α expression level and upregulate copper/zinc superoxide dismutase (Cu/Zn-SOD) and manganese superoxide dismutase (Mn-SOD) expression levels. Furthermore, LPCQZC02 could both reduce and promote beneficial bacteria in the intestines of mice undergoing intense exercise. In conclusion, LPCQZC02 emerged as a functional probiotic and demonstrated a notable advantage over sulfasalazine, a medication for intestinal conditions, in mitigating oxidative inflammation, repairing intestinal barrier damage, and enhancing motor function in mice subjected to strenuous exercise.

The effect of melatonin on capecitabine-induced hepatic and renal toxicity in rats.

Capecitabine (CAPE), an antimetabolite chemotherapy, can induce hepatic and renal toxicity. Melatonin (MEL), a neurohormone, possesses antioxidant, anti-apoptotic and anti-inflammatory effects. This study investigated the impact of MEL on capecitabine-induced hepatic and renal toxicity. Twenty-five male Wistar rats were categorized into five groups for the study. The groups included a control group, MEL10 group (rats receiving daily intraperitoneal injections of 5mg/kg MEL), CAPE 500 group (rats receiving weekly intraperitoneal injections of 500mg/kg CAPE), CAPE + MEL five group, and CAPE + MEL 10 group. All groups were treated for a duration of 6 weeks. Various hematological, serological, biochemical, and histopathological assessments were conducted to evaluate the objective of the study. The administration of CAPE led to significant liver and kidney toxicity, as evidenced by elevated levels of malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), as well as serological markers including AST, ALT, ALP, BUN, and creatinine. CAPE exposure also resulted in a reduction in total antioxidant capacity (TAC) and glutathione peroxidase (GPx) levels. Histological examination revealed hyperemia in both liver and kidney tissues exposed to CAPE. However, treatment with MEL demonstrated positive effects. MEL administration alleviated oxidative stress, reduced levels of liver enzymes, BUN, and creatinine, and ameliorated histopathological degenerations. MEL also increased GPx and TAC levels. Moreover, MEL treatment aided in restoring the body weight that was lost due to CAPE exposure. Our findings indicated that the administration of MEL in rats significantly enhanced the hepatic and renal toxicity induced by CAPE.

Oxalis corniculata and Ficus religiosa mitigates rotenone-induced Parkinson’s disease in Swiss Albino mice: Mechanistic insights and therapeutic potential

Parkinson’s disease (PD) is a neurodegenerative disorder distinguished by the presence of progressive deterioration of the nervous system and is prevalent among the elderly population. The pathological hallmark of PD involves the accumulation of the protein alpha-synuclein and neuronal inflammation, which leads to the degeneration of dopaminergic (DAergic) neurons. In the present study, neuroprotective effect of combinational extract of Ficus religiosa (F. religiosa) and Oxalis corniculata (O. corniculata) L. in a mouse PD model. By giving Rotenone (ROT) on alternate days subcutaneously for 21 days, a disease model was generated. Extracts were administered individually as well as in combination orally 1 hour before ROT (1.5 mg/kg, s.c.) administration. On day 22nd, after sacrificing of animals neurochemical assays [total protein content (TPC), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), nitrite (NO)], neurotransmitter analysis, and histology of the brain were performed. Results of the study showed a significant increase in the level of TPC, CAT, SOD, GSH, and dopamine in substantia nigra and a significant reduction of MDA, NO, and glutamate after administration of F. religiosa and O. corniculata in combination (200 + 500 mg/kg, p.o.) in a ROT induced model. This study demonstrated that a combination of F. religiosa and O. corniculata improved motor symptoms and reduced dopaminergic neuron death in mice challenged with ROT.

Use of Lactoferrin Supplement as an Efficient Antioxidant to Ameliorate the Effects of Mercury-induced Oxidative Stress in Male Wistar Rats

Background: The present study was carried out to test the antioxidant activity of lactoferrin as a dietary supplement to alleviate the effects of oxidative stress induced by mercury toxicity. Hematological and biochemical assays were employed to evaluate the ameliorating effects of lactoferrin. Methods: Sixty male Wistar rats were allotted randomly and equally into three groups; animals in Group 1 served as untreated control, animals in Group 2 were administered orally with mercuric chloride (HgCl2) at the dose of 6 mg/kg bw/day, and animals in Group 3 were administered with HgCl2 at the same dose and orally dosed with lactoferrin (400 mg/kg bw/day). Hematological indices (erythrocytic and total leukocytic counts, hemoglobin concentration%, and packed cell volume, (PCV%), and biochemical parameters (serum and homogenates of liver and kidney tissues) were assessed in all animals. Serum and tissue homogenate levels of total thiols, glutathione (GSH), catalase, and total antioxidant capacity (TAC) represented the antioxidant markers. The oxidation markers were represented by H2O2 and malondialdehyde (MDA). Results: Compared to the untreated control group, animals in Group 2 (administered with HgCl2) exhibited significantly increased levels of serum enzymes (alanine transferase (ALT), aspertate transferase (AST), and alkaline phosphatase), urea, blood urea nitrogen, creatinine, H2O2, and MDA. These animals showed significantly decreased levels of erythrocytic and total leukocytic counts, hemoglobin concentration, PCV%, total proteins, total thiols, GSH, catalase, and TAC. The hematological and biochemical changes were comparatively reversed toward the control levels in animals of Group 3 (administered with HgCl2 and orally dosed with lactoferrin). The reversed levels of hematological and biochemical parameters were significantly different compared to Group 2. Conclusions: Based on the encountered amelioration of the assayed hematological and biochemical parameters in animals treated with HgCl2 and given lactoferrin, it could be concluded that lactoferrin as a dietary supplement might function as an efficient antioxidant to alleviate the oxidative stress induced by mercury toxicity.

The Dietary Lipid Requirement for Ovarian Maturation and Health in Female Giant River Prawn, Macrobrachium rosenbergii Broodstock

The dietary lipid level is closely associated with ovarian maturation of broodstock. However, optimal lipid requirements during broodstock gonad development for aquatic animals remain limited. In order to assess the impact of dietary lipid levels (6%, 8%, 10%, 12%, and 14% lipid, denoted as L6%, L8%, L10%, L12%, and L14%) on the ovarian maturation, antioxidant status, and messenger RNA (mRNA) expression of genes involved in the lipid metabolism of Macrobrachium rosenbergii broodstock (initial weight 10.53 ± 1.97 g), this study carried out an 8‐week feeding experiment. The findings showed that while there was no significant difference in the survival rate across the groups (p &gt; 0.05), the weight gain observed in prawns fed the 8% lipid‐level diet was significantly higher than those fed other diets (p &lt; 0.05). The hepatosomatic index and the gonadosomatic index showed a significant increase with the rise in dietary lipid level (p &lt; 0.05). More ovaries from M. rosenbergii broodstock reached stages Ⅲ and Ⅳ after being supplemented with dietary lipid levels between 8% and 14%. Serum glucose content did not show any significant difference among all groups (p &gt; 0.05), but serum triglyceride and total cholesterol content increased followed by a decreasing trend with increasing levels of dietary lipids, both peaking in the prawns fed a 10% lipid‐level diet. Furthermore, the progesterone (PROG) and 17β‐estradiol (E2) content of prawns fed the 10% and 12% lipid‐level diets were significantly higher compared to other groups (p &lt; 0.05). Based on serum E2 and PROG content, the optimal lipid level needed for maximal ovarian maturation was determined to be 11.79% and 10.88%, respectively. Moreover, there were more endogenous vitellogenic oocytes in prawns fed 8% and 10% lipid‐level diets, with a more compact arrangement compared to the less tightly arranged structure of the ovarian tissue in prawns fed other diets. With the increase in dietary lipid levels, there was a significant increase in the activity of superoxide dismutase. The activities of total antioxidant capacity and glutathione peroxidase initially increased and then decreased significantly, peaking at prawns fed 8% and 10% lipid‐level diets, respectively (p &lt; 0.05). The malondialdehyde content reached its lowest point in prawns fed a diet containing 10% lipid. In addition, the mRNA expressions of hepatopancreatic diacylglycerol acyltransferase and acetyl‐CoA carboxylase showed the highest values in prawns fed a 10% lipid diet. Conversely, there was a significant decrease in the mRNA expression of carnitine palmitoyltransferase‐1a in the hepatopancreatic as dietary lipid levels increased. The highest mRNA expression of fatty acid‐binding proteins was observed in prawns fed an 8% lipid diet. In conclusion, dietary lipid levels ranging from 8% to 11.79% are beneficial for ovarian maturation and health of M. rosenbergii broodstock.

Impacts of enzymes and probiotic in improving the utilization of sieved olive pulp meal in growing rabbit diets

Objective: This research assesses the utilization of sieved olive pulp (SOP) in the diet of growing rabbits through the use of an exogenous enzyme or dry yeast as a pretreatment. Materials and Methods: One hundred sixty-eight male V-Line rabbits aged 5 weeks (weighing 550 ± 25 gm) were randomly divided into seven groups with eight replicates each as follows: the control group was fed a basal diet without supplementation; while the other six groups were fed basal diets containing 20% and 25% of SOP and supplemented with 0.1 gm/kg Econase (E), 0.5 gm/kg dry yeast (Y), and a combination of both. The experiment lasted for 8 weeks. Results: The results indicated that supplementation of E, Y, and EY into rabbit diets containing SOP improved live body weight, body weight gain, feed conversion ratio, and nutrient digestibil¬ity. A higher dressing percentage was observed in the groups fed a 20% and 25% SOP diet sup¬plemented with EY (p &lt; 0.05). The treated groups showed an increase in total protein, albumin, globulin, A/G ratio, total antioxidant capacity, superoxide dismutase, and glutathione peroxidase (p &lt; 0.05), while there was a significant decrease in triglycerides, total cholesterol, and malondi¬aldehyde levels (p &lt; 0.05) compared to the control. Rabbit groups fed an SOP diet supplemented with E, Y, or EY demonstrated higher (p &lt; 0.05) economic efficiency compared to the control. Conclusion: Supplementing the diet of rabbits containing SOP with exogenous enzymes and/or dry yeast enhances the nutritional value of SOP while improving rabbit performance, nutrient digestibility, and antioxidant status.

The effect of dietary eugenol nano-emulsion supplementation on growth performance, serum metabolites, redox homeostasis, immunity, and pro-inflammatory responses of growing rabbits under heat stress.

Heat stress (HS) is a main abiotic stress factor for the health and welfare of animals. Recently, the use of nano-emulsion essential oils exhibited a promising approach to mitigate the detrimental impacts of abiotic and biotic stresses, ultimately contributing to the global aim of sustainable livestock production. The current study was piloted to assess the impact of eugenol nano-emulsion (EUGN) supplementation on growth performance, serum metabolites, redox homeostasis, immune response, and pro-inflammatory reactions in growing rabbits exposed to HS. A total of 100 male weaning rabbits aged 35 days were divided into 4 treatments. Rabbits were fed the diet with EUGN at different concentrations: 0 (control group; EUGN0), 50 (EUGN50), 100 (EUGN100), and 150 (EUGN150) mg/kg diet for 8 weeks under summer conditions. Dietary EUGN levels significantly improved (p < 0.05) the body weight, body weight gain, carcass weights, and improved feed conversion ratio of rabbits. EUGN supplementation significantly increased Hb, platelets, and red blood cells , while the mean corpuscular hemoglobin and eosinophils were significantly decreased compared to the control one. Compared with EUGN0 stressed rabbits, all EUGN-experimental groups had a reduction in levels of total glycerides (p < 0.01), uric acid, total bilirubin, direct bilirubin, and gamma-glutamyl transpeptidase (p < 0.01). Total antioxidant capacity and glutathione peroxidase were significantly improved by EUGN treatment when compared to the control one (p < 0.01), while the EUGN100 exhibited the greatest levels of catalase. Lipid peroxidation (malondialdehyde) was significantly decreased in EUGN-treated groups. All pro-inflammatory cytokines serum interleukin 4, Interleukin 1β, and tumor necrosis factor alpha were considerably decreased after dietary EUGN supplementation (p < 0.05). The serum concentrations of immunoglobulins (IgG and IgM) were significantly improved in rabbits of the EUGN150 group. This study shows that EUGN can be used as a novel feed additive to enhance the growth performance, immune variables, and antioxidants, and reduce the inflammatory response of growing rabbits exposed to thermal stress.

Pickle water ameliorates castor oil-induced diarrhea in mice by regulating the homeostasis of the gut microbiota and intestinal mucosal barrier.

Diarrhea is a common clinical condition that can potentially be fatal. Current treatment options often have side effects, such as constipation and vomiting, and there remains a need for more effective therapies. Pickled vegetables, a famous traditional food in China, have been suggested in clinical studies to alleviate diarrhea in children, particularly through the use of pickle water (PW). However, the pharmacological effects and mechanisms of PW on intestinal health remain unclear. This study aimed to explore the protective effects of PW on castor oil-induced diarrhea in ICR mice and to investigate its potential mechanisms. To evaluate the antidiarrheal effects of PW, we used a castor oil-induced diarrhea model in ICR mice. Various indices were measured to assess the severity of diarrhea. After euthanizing the mice, oxidative stress markers in the ileum were assessed using biochemical methods, and the expression of tight junction-related proteins in the ileum was analyzed using Western blot. Additionally, 16S rRNA high-throughput sequencing was used to evaluate the diversity and composition of the intestinal flora. The results showed that PW supplementation reduced body weight without significantly affecting organ index and liver function in the castor oil-induced diarrhea mice. PW also effectively reduced the dilution rate, diarrhea index, average loose stool grade, propelling distance of carbon powder, and intestinal propulsive rate while improving the pathological abnormality in the ileum. Furthermore, PW enhanced the activities of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX), and catalase (CAT) while reducing malonaldehyde (MDA) levels. PW also increased the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin in the ileum. Additionally, the analysis of 16S rDNA revealed that PW increased both α and β diversity, improved the composition of the intestinal flora, and restored it to a normal level. Collectively, dietary PW administration ameliorates Castor oil-induced diarrhea by restoring tight junctions between intestinal mucosal cells, suppressing oxidative stress, and regulating the composition of intestinal flora. These findings suggest that PW may be a promising strategy for managing diarrhea.

Metodologias para indicar estresse causado por jejum em poedeiras comerciais

ABSTRACT: Plasma corticosterone concentration (CORT), heterophil:lymphocyte ratio (H:L), catalase activity (CAT), total glutathione concentration (GSH), and thiobarbituric acid reactive substance levels (TBARS) were evaluated in 48 Hy-Line Brown laying hens, at 79 weeks of age, after being fasted for 10 consecutive days. Blood was collected on days zero, two, four, six, eight, and 10 of fasting, and a completely randomized design was adopted, with eight replicates on each day of collection, with each bird being an experimental unit. The time of maximum stress was determined for each method, using the polynomial regression analysis. The Pearson correlation analysis was also performed to determine whether the methods were interchangeable. CORT and GSH concentrations indicated that the time of maximum stress occurred at 4.3 days of fasting, whereas, the H:L and CAT activity indicated that the time of maximum stress occurred at 10 days of fasting. The malondialdehyde concentration detected by the TBARS method was highest at day zero and lowest at day 5.5 of fasting, but this method was not a reliable measure of stress. The low Pearson correlation coefficients observed among the methods made it impossible to designate only one of the tested methods as a replacement for the others, to measure the stress in laying hens during fasting.

Biochemical and Histopathological Evaluation of Systemic and Ocular Toxicity of Favipiravir in Rats

Purpose: Favipiravir used against COVID-19 is an antiviral drug that causes adverse reactions such as hyperuricemia, liver damage and hematopoetic toxicity. The aim of the study was to investigate the systemic and ocular side-effects of favipiravir in rats, for the first time. Materials and Methods: A total of 18 albino male Wistar rats were used in the study. The rats were divided into 3 groups as the healthy group (HG), the group given 50 mg/kg/day favipiravir (FAV50), and the group given 200 mg/kg/day favipiravir (FAV200). These doses were given to the experimental groups for one week. At the end of the experiment histopathological examinations were performed on the conjunctiva and sclera of the eye. In addition, malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) levels were measured in blood samples taken from rats. Results: Compared to HG, the MDA (1.37 ± 0.61 vs 4.82 ± 1.40 µmol/ml), IL-1β (2.52 ± 1.14 vs 6.67 ± 1.99 pg/ml) and TNF-α levels (3.28 ± 1.42 vs 8.53 ± 3.06 pg/ml) of the FAV200 group were higher. The levels of tGSH (7.58 ± 1.98 vs 2.50 ± 0.98 nmol/ml) and SOD (13.63 ± 3.43 vs 3.81 ± 1.43 U/ml) the FAV200 group were lower than the HG (p < 0.05, for all). The degree of damage to the cornea and sclera of the FAV200 group was quite high according to HG (p < 0.001). Conclusion: Favipiravir can cause damage to rat conjunctiva and sclera by increasing oxidant stress and inflammation at high dose.