Protocatechuic acid reverses myocardial infarction mediated by ß-adrenergic agonist via regulation of Nrf2/HO-1 pathway, inflammatory, apoptotic, and fibrotic events.

Myocardial infarction (MI) is an instant ischemic death of cardiomyocytes that remains a major global cause of mortalities. MI is accompanied by oxidative, inflammatory, apoptotic, and fibrotic insults. Protocatechuic acid (PCA) is a polyphenolic compound with various potent biological activities. In this study, we explored the possible cardioprotective role of PCA against isoproterenol (ISO)-mediated MI. Rats were either injected with ISO (85 mg/kg, subcutaneously) or pretreated with PCA (100 or 200 mg/kg, orally). PCA supplementation markedly normalized ISO-induced disturbed cardiac function markers (creatine kinase-MB, lactate dehydrogenase, and troponin T). Notably, PCA administration exerted remarkable increases in glutathione and its derived enzymes, superoxide dismutase, and catalase, as well as decreases in malondialdehyde and nitric oxide levels in the injured cardiac tissue. The molecular findings validated the augmented cellular antioxidative capacity by PCA via increasing the gene expressions of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1. The cardioprotective efficacy of PCA extended to suppress cardiac inflammation as demonstrated by the decreased levels of tumor necrosis factor-alpha, interleukin-1 beta, and nuclear factor kappa B. Additionally, PCA prevented cardiomyocyte loss and fibrosis by decreasing Bax, caspase-3, transforming growth factor-ß1 and matrix metalloproteinase-9, and enhancing B-cell lymphoma 2 and tissue inhibitors of metalloproteinase-3. The cardiac histological screening further confirmed the PCA's protective action. The obtained data recommend PCA as an alternative therapeutic agent to attenuate the molecular, biochemical, and histological alterations associated with MI development.

Apigenin protects from hepatorenal damage caused by lead acetate in rats.

Exposure to lead (Pb) is associated with serious health problems including hepatorenal toxicity. Apigenin is a natural-sourced flavonoid with promising antioxidant and anti-inflammatory effects. In this research, we investigated the potential protective role of apigenin against lead acetate (PbAc)-induced hepatorenal damage. Thus, this experiment studied the exposure of male Wistar Albino rats to apigenin and/or PbAc and their effects in comparison to the control rats. Apigenin administration decreased the levels of Pb and prevented the histopathological deformations in liver and kidney tissues following PbAc exposure. This was confirmed by the normalized levels of liver and kidney function markers. Additionally, apigenin inhibited significantly oxidative reactions through upregulating Nrf2 and HO-1, and activating their downstreamed antioxidants accompanied by a marked depletion of pro-oxidants. Moreover, apigenin decreased the elevated pro-inflammatory cytokines and inhibited cell loss in liver and kidney tissues in response to PbAc intoxication in both tissues. The obtained results demonstrated that apigenin could be used to attenuate the molecular, biochemical, and histological alterations associated with Pb exposure due to its potent antioxidant, anti-inflammatory, and antiapoptotic effects.

Neuroprotective efficacy of the bacterial metabolite, prodigiosin, against aluminium chloride-induced neurochemical alternations associated with Alzheimer's disease murine model: Involvement of Nrf2/HO-1/NF-κB signaling.

Prodigiosin (PDG) is a bacterial metabolite with numerous biological and pharmaceutical properties. Exposure to aluminium is considered a root etiological factor in the pathological progress of Alzheimer's disease (AD). Here, in this investigation, we explored the neuroprotective potential of PDG against aluminium chloride (AlCl3 )-mediated AD-like neurological alterations in rats. For this purpose, rats were gavaged either AlCl3 (100 mg/kg), PDG (300 mg/kg), or both for 42 days. As a result of the analyzes performed on the hippocampal tissue, it was observed that AlCl3 induced biochemical, molecular, and histopathological changes like those related to AD. PDG pre-treatment significantly decreased acetylcholinesterase activity and restored the levels of brain-derived neurotrophic factor, monoamines (dopamine, norepinephrine, and serotonin), and transmembrane protein (Na+ /K+ -ATPase). Furthermore, PDG boosted the hippocampal antioxidant capacity, as shown by the increased superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione contents. These findings were accompanied by decreases in malondialdehyde and nitric oxide levels. The antioxidant effect may promote the upregulation of the expression of antioxidant genes (Nrf2 and HO-1). Moreover, PDG exerted notable anti-inflammatory effects via the lessening of interleukin-1 beta, tumor necrosis factor-alpha, cyclooxygenase-2, nuclear factor kappa B, and decreases in the gene expression of inducible nitric oxide synthase. In addition, noteworthy decreases in pro-apoptotic (Bax and caspase-3) levels and increases in anti-apoptotic (Bcl-2) biomarkers suggested an anti-apoptotic effect of PDG. In support, the hippocampal histological examination validated the aforementioned changes. To summarize, the promising neuromodulatory, antioxidative, anti-inflammatory, and anti-apoptotic activities of PDG establish it as a potent therapeutic option for AD.

Oleuropein protects against lipopolysaccharide-induced sepsis and alleviates inflammatory responses in mice.

Sepsis results from a major systemic inflammatory response and can induce disorders in multiple organs. The present study evaluated the potential protective effects of oleuropein (OLE) against hyperinflammatory responses during lipopolysaccharide (LPS)-induced sepsis in mice. Sixty male Balb/c mice were randomly categorized into five groups of 12 animals each: control, intraperitoneally injected with OLE (50 mg/kg), injected with LPS (10 mg/kg, intraperitoneal), and two groups administered OLE (25 and 50 mg/kg) for 3 days prior to LPS injection. Twenty-four hours after lipopolysaccharide injection, the animals were sacrificed. Serum, liver, and kidney tissue samples were collected for biochemical analyses, histopathological examinations, and investigation of inflammation-related gene expression. OLE pretreatment significantly reduced liver damage parameters (alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase) and kidney damage parameters (blood urea nitrogen, creatinine, and kidney injury molecule-1) in the septic mice. OLE pretreatment ameliorated LPS-induced liver and kidney histological changes. OLE significantly mitigated the increased levels of malondialdehyde in the liver and kidneys and reduced levels of reduced glutathione induced by LPS. LPS injection also resulted in increased expression of the proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) and inflammation-related genes (Nos2, Hmgb1, Mpo, Cd46, Map2k4, and Map2k7) in the hepatic and renal tissues. OLE reduced these expressions to ameliorate the inflammatory response. Moreover, OLE pretreatment enhanced the survival rate of septic mice. In conclusion, OLE alleviated the inflammatory response to protect against LPS-induced sepsis in mice.

Nephroprotective effect of Pleurotus ostreatus extract against cadmium chloride toxicity in rats.

Cadmium, present in the environment, accumulates in different organs of animals and humans, and has deleterious effects on the kidney. In this study, we investigated the protective effects of the methanolic extract of Pleurotus ostreatus in comparison with silymarin on renal function in cadmium-intoxicated rats for five days. Rats intraperitoneally injected with cadmium chloride (1 mg/kg). These rats were treated with either P. ostreatus extract (200 mg/kg) or silymarin to investigate the protective effects of the extract. Cadmium treatment induced significant histopathological impairments and increased cadmium levels, DNA fragmentation, and renal oxidative stress. However, treatment with P. ostreatus extract or silymarin improved the pathology, reduced the level of cadmium in renal tissue, and restored DNA fragmentation. In addition, a significant reduction in lipid peroxidation and reactive oxygen species levels, and a significant increase in the levels of glutathione and catalase activity were observed. Thus, protective effects of P. ostreatus extract to its components. Chromatographic analysis of the P. ostreatus confirmed the presence of five phenolics (gallic acid, chlorogenic acid, catechin, propyl gallate, and cinnamic acid) that exhibit strong antioxidant properties as free radical scavengers. Therefore, our findings demonstrate that treatment with P. ostreatus extract protects against cadmium-induced nephrotoxicity in female rats.

Neurochemical alterations following the exposure to di-n-butyl phthalate in rats.

Due to its ability to cross blood brain barrier and placenta, dibutyl phthalate (di-n-butyl phthalate, DBP) is expected to cause severe side effects to the central nervous system of animals and humans. A little data is available about the potential DBP neurotoxicity; therefore, this work was designed to investigate the brain tissue injury induced by DBP exposure. Forty Wister albino rats were allocated randomly into 4 groups (10 rats each). Group 1 served as control and the rats administered with physiological saline (0.9% NaCl) orally for 12 weeks. Groups 2, 3 and 4 were orally treated with DPB (100, 250 and 500 mg/kg) respectively for 12 weeks. DBP-intoxicated rats showed a disturbance in the oxidative status in cerebral cortex, striatum and brainstem, as represented by the elevated oxidants [malondialdehyde (MDA), nitric oxide (NO), 8-hydroxy-2-deoxyguanosine (8-OHdG)] and the decreased antioxidant molecules [reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR)]. DBP also enhanced a pro-inflammatory state through increasing the release of tumor necrosis factor- α (TNF-α) and interleukin-1ß (IL-1ß). The increase of these cytokines was associated with the increase of pro-apoptotic proteins [Bcl-2 associated X protein (Bax) and caspase-3] and the decrease of the anti-apoptotic protein, B cell lymphoma 2 (Bcl-2). In addition, the levels of norepinephrine (NE), dopamine (DA) and acetylcholine esterase (AChE) activity were decreased. This was accompanied by the alterations in the major excitatory and inhibitory amino acids neurotransmitters levels. The present findings indicated that DBP could exert its neuronal damage through oxidative stress, DNA oxidation, neuroinflammation, activation of apoptotic proteins and altering the monoaminergic, cholinergic and amino acids transmission.

Soursop fruit extract mitigates scopolamine-induced amnesia and oxidative stress via activating cholinergic and Nrf2/HO-1 pathways.

Current therapeutic interventions for memory loss are inadequate and are associated with numerous adverse effects. There is an urgent need for new alternative agents for the treatment of memory loss and related disorders. Here, we investigated the potential neuroprotective role of soursop fruit extract (SSFE) in scopolamine (SCO)-induced amnesia and oxidative damage in the hippocampus of rats. Thirty-five rats were randomly allocated into 5 groups: control, SCO, SSFE, SCO, SSFE+SCO and N-acetylcysteine (NAC) + SCO. SCO-treatment increased acetylcholine esterase activity and decreased hippocampal levels of acetylcholine, serotonin, dopamine, norepinephrine, and histamine. The level of ATP increased. SCO-treated rats showed a disturbance in oxidative status, which was evident through the increase in malondialdehyde, and nitrites/nitrates and a decrease in cellular antioxidant molecules including glutathione, superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. A disturbance was also observed via downregulation of the nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 defense pathways. SCO-treatment enhances a neuroinflammatory state, as indicated by the release of tumor necrosis factor- α and interleukin-1ß and increased inducible nitric oxide synthase and mRNA expression. SCO-treatment decreased the expression of the anti-apoptotic protein, B cell lymphoma 2 and increased the expression of the pro-apoptotic protein, Bcl-2 associated X protein, caspase-3 and cytochrome c in hippocampal neurons. SSFE pretreatment markedly ameliorated hippocampal changes. Our findings revealed that SSFE exerts its potential anti-amnestic effect mainly through the activation of the cholinergic system and Nrf2/HO-1 pathway.

Asiatic acid rescues intestinal tissue by suppressing molecular, biochemical, and histopathological changes associated with the development of ulcerative colitis.

Asiatic acid (AA) is a polyphenolic compound with potent antioxidative and anti-inflammatory activities that make it a potential choice to attenuate inflammation and oxidative insults associated with ulcerative colitis (UC). Hence, the present study aimed to evaluate if AA can attenuate molecular, biochemical, and histological alterations in the acetic acid-induced UC model in rats. To perform the study, five groups were applied, including the control, acetic acid-induced UC, UC-treated with 40 mg/kg aminosalicylate (5-ASA), UC-treated with 20 mg/kg AA, and UC-treated with 40 mg/kg AA. Levels of different markers of inflammation, oxidative stress, and apoptosis were studied along with histological approaches. The induction of UC increased the levels of lipid peroxidation (LPO) and nitric oxide (NO). Additionally, the nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant proteins [catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR)] were down-regulated in the colon tissue. Moreover, the inflammatory mediators [myeloperoxidase (MPO), monocyte chemotactic protein 1 (MCP1), prostaglandin E2 (PGE2), nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß)] were increased in the colon tissue after the induction of UC. Notably, an apoptotic response was developed, as demonstrated by the increased caspase-3 and Bax and decreased Bcl2. Interestingly, AA administration at both doses lessened the molecular, biochemical, and histopathological changes following the induction in the colon tissue of UC. In conclusion, AA could improve the antioxidative status and attenuate the inflammatory and apoptotic challenges associated with UC.

Molecular detection and characterization of Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi infections in dromedary camels (Camelus dromedaries) in Egypt.

Introduction: Few studies have investigated the occurrence of microeukaryotic gut parasites in dromedary camels in Egypt, and the majority of these investigations are based on microscopic analysis of fecal material. Methods: Herein, we assessed the occurrence, molecular diversity, and zoonotic potential of protozoan (Cryptosporidium spp. and Giardia duodenalis) and microsporidian (Enterocytozoon bieneusi) pathogens in individual fecal samples (n = 102) of dromedary camels with (n = 26) and without (n = 76) diarrhea from Aswan Governorate, Upper Egypt. Other factors possibly associated with an increased risk of infection (geographical origin, sex, age, and physical condition) were also analyzed. The SSU rRNA or ITS genes were targeted by molecular (PCR and Sanger sequencing) techniques for pathogen detection and species identification. Results and discussion: The most abundant species detected was G. duodenalis (3.9%, 4/102; 95% CI: 1.1-9.7), followed by Cryptosporidium spp. (2.9%, 3/102; 95% CI: 0.6-8.4). All samples tested negative for the presence of E. bieneusi. Sequence analysis data confirmed the presence of zoonotic C. parvum (66.7%, 2/3) and cattle-adapted C. bovis (33.3%, 1/3). These Cryptosporidium isolates, as well as the four Giardia-positive isolates, were unable to be amplified at adequate genotyping markers (Cryptosporidium: gp60; Giardia: gdh, bg, and tpi). Camels younger than 2 years old were significantly more likely to harbor Cryptosporidium infections. This connection was not statistically significant, although two of the three cryptosporidiosis cases were detected in camels with diarrhea. The spread of G. duodenalis infections was unaffected by any risk variables studied. This is the first report of C. parvum and C. bovis in Egyptian camels. The finding of zoonotic C. parvum has public health implications since camels may function as sources of oocyst pollution in the environment and potentially infect livestock and humans. Although preliminary, this study provides useful baseline data on the epidemiology of diarrhea-causing microeukaryotic parasites in Egypt. Further research is required to confirm and expand our findings in other animal populations and geographical regions of the country.

Corrigendum: Melatonin ameliorates serobiochemical alterations and restores the cardio-nephro diabetic vascular and cellular alterations in streptozotocin-induced diabetic rats.

[This corrects the article DOI: 10.3389/fvets.2023.1089733.].

Melatonin downregulates the increased hepatic alpha-fetoprotein expression and restores pancreatic beta cells in a streptozotocin-induced diabetic rat model: a clinical, biochemical, immunohistochemical, and descriptive histopathological study.

Background: Diabetes mellitus (DM) is a chronic metabolic disorder. Hepatopathy is one of the serious effects of DM Melatonin (MT) is a potent endogenous antioxidant that can control insulin output. However, little information is available about the potential association between melatonin and hepatic alpha-fetoprotein expression in diabetes. Objective: This study was conducted to assess the influence of MT on diabetes-related hepatic injuries and to determine how ß-cells of the pancreas in diabetic rats respond to MT administration. Materials and methods: Forty rats were assigned to four groups at random (ten animals per group). Group I served as a normal control group. Group II was induced with DM, and a single dose of freshly prepared streptozotocin (45 mg/kg body weight) was intraperitoneally injected. In Group III, rats received 10 mg/kg/day of intraperitoneal melatonin (IP MT) intraperitoneally over a period of 4 weeks. In Group IV (DM + MT), following the induction of diabetes, rats received MT (the same as in Group III). Fasting blood sugar, glycosylated hemoglobin (HbA1c), and serum insulin levels were assessed at the end of the experimental period. Serum liver function tests were performed. The pancreas and liver were examined histopathologically and immunohistochemically for insulin and alpha-fetoprotein (AFP) antibodies, respectively. Results: MT was found to significantly modulate the raised blood glucose, HbA1c, and insulin levels induced by diabetes, as well as the decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, MT attenuated diabetic degenerative changes in the pancreas and the hepatic histological structure, increased the ß-cell percentage area, and decreased AFP expression in the liver tissue. It attenuated diabetes-induced hepatic injury by restoring pancreatic ß-cells; its antioxidant effect also reduced hepatocyte injury. Conclusion: Collectively, the present study confirmed the potential benefits of MT in downregulating the increased hepatic alpha-fetoprotein expression and in restoring pancreatic ß-cells in a streptozotocin-induced diabetic rat model, suggesting its promising role in the treatment of diabetes.

Protective effect of quercetin against 5-fluorouracil-induced cardiac impairments through activating Nrf2 and inhibiting NF-κB and caspase-3 activities.

5-Fluorouracil (5-FU) is a chemotherapy used to treat many types of cancer. Cardiotoxicity is one of the common drawbacks of 5-FU therapy. Quercetin (Qu) is a bioflavonoid with striking biological activities. This research aimed to assess the ameliorative effect of Qu against 5-FU-mediated cardiotoxicity. Thirty-five rats were allocated into five groups: control group (normal saline), 5-FU group (30 mg/kg, intraperitoneally), Qu group (50 mg/kg, oral), 25 mg/kg Qu+5-FU group, and 50 mg/kg Qu+5-FU. The experimental animals were received the above-mentioned drugs for 21 days. Results showed that 5-FU significantly elevated creatine kinase, lactate dehydrogenase, serum cholesterol and triglyceride, and upregulated troponin and renin mRNA expression. Additionally, cardiac oxidant/antioxidant imbalance was evident in elevated oxidants (malondialdehyde and nitric oxide) and depleted antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione). 5-FU also downregulated the gene expression of nuclear factor erythroid 2-related factor 2. Furthermore, 5-FU significantly increased cardiac pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and upregulated gene expression of nuclear factor kappa-B. 5-FU significantly enhanced cardiac apoptosis through upregulating caspase-3 expression and downregulating B-cell lymphoma 2. Immunohistochemical and histopathological examinations verified the above-mentioned findings. However, all these changes were significantly ameliorated in Qu pre-administered rats. Conclusively, Qu counteracted 5-FU-mediated cardiotoxicity through potent antioxidant, anti-inflammatory, and anti-apoptotic effects.

Thymoquinone counteracts oxidative and inflammatory machinery in carrageenan-induced murine paw edema model.

Thymoquinone (TQ) is an active constituent in Nigella sativa (black cumin) and is extensively reported for its distinguished antioxidant and anti-inflammatory bioactivities. Despite the local protective response of acute inflammation, it contributes to the development of various disease conditions such as cell death, organ damage, or carcinogenesis. Hence, in this study, the effects of orally administered TQ (50 mg/kg and 100 mg/kg) for 14 days against edema development, oxidative stress, and inflammation were investigated in paw edema induced by carrageenan in mice. Indomethacin (10 mg/kg) was used as a reference drug. The results revealed that TQ reduced the paw edema volume in a time-dependent manner, attenuated acetic acid-provoked writhing movements, and reduced xylene-triggered ear edema. Hematological findings revealed marked normalization of altered counts of WBCs, and platelets. Furthermore, paw tissue levels of malondialdehyde and nitric oxide showed marked decreases together with increases in nuclear factor erythroid 2-related factor 2, glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase after TQ administration. Additionally, TQ decreased pro-inflammatory mediators, such as interleukin-1 beta, tumor necrosis factor-alpha, interleukin-6, monocyte chemoattractant protein-1, C-reactive protein, myeloperoxidase, and nuclear factor kappa-B in the inflamed paw tissue. Moreover, appreciable decreases were recorded in cyclooxygenase-2 and its product prostaglandin E2 and the immune reaction of tumor necrosis factor-alpha in TQ-treated mice. Histopathological findings further validated the potential antiedematous, anti-inflammatory power of TQ in inflamed tissues. Conclusively, the results encourage the potent application of TQ to subside acute inflammatory events because of its striking antioxidant and anti-inflammatory properties in inflamed paw tissue.

Melatonin ameliorates serobiochemical alterations and restores the cardio-nephro diabetic vascular and cellular alterations in streptozotocin-induced diabetic rats.

Melatonin possesses a wide range of pharmacological activities, including antidiabetic properties. Diabetes mellitus (DM) induces several physiopathological changes in body organs, which could be observed lately after systemic failure. In the current study, we aimed to investigate the serobiochemical changes and the histopathological picture in the diabetic heart and the kidney early before chronic complications and highlight the association between hyperglycemia, glomerular alterations, and cardiovascular changes. In addition, the role of melatonin in the treatment of cardio-nephro diabetic vascular and cellular adverse changes in streptozotocin-induced diabetic rats was also studied. A total of 40 mature Wistar albino rats were distributed into five groups; (1) control untreated rats, (2) diabetic mellitus untreated (DM) rats, in which DM was induced by the injection of streptozotocin (STZ), (3) control melatonin-treated (MLT), (4) melatonin-treated diabetic (DM + MLT) rats, in which melatonin was injected (10 mg/kg/day, i.p.) for 4 weeks, and (5) insulin-treated diabetic (DM + INS) rats. The serum biochemical analysis of diabetic STZ rats showed a significant (P < 0.05) increase in the concentrations of blood glucose, total oxidative capacity (TOC), CK-MB, endothelin-1, myoglobin, H-FABP, ALT, AST, urea, and creatinine as compared to control rats. In contrast, there was a significant (P < 0.05) decrease in serum concentration of insulin, total antioxidative capacity (TAC), total nitric oxide (TNO), and total protein level in DM rats vs. the control rats. Significant improvement in the serobiochemical parameters was noticed in both (DM + MLT) and (DM + INS) groups as compared with (DM) rats. The histological examination of the DM group revealed a disorder of myofibers, cardiomyocyte nuclei, and an increase in connective tissue deposits in between cardiac tissues. Severe congestion and dilation of blood capillaries between cardiac muscle fibers were also observed. The nephropathic changes in DM rats revealed various deteriorations in glomeruli and renal tubular cells of the same group. In addition, vascular alterations in the arcuate artery at the corticomedullary junction and interstitial congestion take place. Melatonin administration repaired all these histopathological alterations to near-control levels. The study concluded that melatonin could be an effective therapeutic molecule for restoring serobiochemical and tissue histopathological alterations during diabetes mellitus.

Silver Nanoparticles Enhance Oxidative Stress, Inflammation, and Apoptosis in Liver and Kidney Tissues: Potential Protective Role of Thymoquinone.

Silver nanoparticles (AgNPs) are the most common nanomaterials in consumer products. Therefore, it has been crucial to control AgNPs toxicological effects to improve their safety and increase the outcome of their applications. This work investigated the possible protective effect of thymoquinone (TQ) against AgNPs-induced hepatic and renal cytotoxicity in rats. Serum markers of liver and kidney functions as well as liver and kidney oxidative stress status, pro-inflammatory cytokines, apoptosis markers, and histopathology were assessed. TQ reversed AgNPs-induced elevation in serum liver and kidney function markers, including aspartate transaminase, alanine transaminase, urea, and creatinine. Moreover, TQ co-administration with AgNPs alleviates hepatic and renal oxidative insults by decreasing MDA and NO levels with a significant increase in the activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione recycling enzymes peroxidase and reductase) compared to AgNPs-treated rats. Besides, TQ upregulated hepatic and renal Nrf2 gene expression in AgNPs-intoxicated rats. Furthermore, TQ co-administration decreased the hepatic and renal pro-inflammatory mediators represented by IL-1ß, TNF-α, TGF-ß, and NF-κB levels. Besides, TQ co-administration decreased apoptotic protein (Bax) levels and increased the anti-apoptotic protein (Bcl-2) levels. These findings were confirmed by the histopathological examination of hepatic and renal tissues. Our data affirmed the protective effect of TQ against AgNPs cytotoxicity and proposed a possible mechanism of TQ antioxidant, anti-inflammatory, and anti-apoptotic effects. Consequently, we could conclude that using TQ might control AgNPs toxicological effects, improve their safety, and increase the outcome of their applications.

Therapeutic antischizophrenic activity of prodigiosin and selenium co-supplementation against amphetamine hydrochloride-induced behavioural changes and oxidative, inflammatory, and apoptotic challenges in rats.

Schizophrenia (SCZ), a multifactorial neuropsychiatric disorder, is treated with inefficient antipsychotics and linked to poor treatment outcomes. This study, therefore, investigated the combined administration of prodigiosin (PDG) and selenium (Na2SeO3) against SCZ induced by amphetamine (AMPH) in rats. Animals were allocated into four groups corresponding to their respective 7-day treatments: control, AMPH (2 mg/kg), PDG (300 mg/kg) + Na2SeO3 (2 mg/kg), and AMPH + PDG + Na2SeO3. The model group exhibited biochemical, molecular, and histopathological changes similar to those of the SCZ group. Contrastingly, co-administration of PDG and Na2SeO3 significantly increased the time for social interaction and decreased AChE and dopamine. It also downregulated the gene expression of NMDAR1 and restored neurotrophin (BDNF and NGF) levels. Further, PDG combined with Na2SeO3 improved the antioxidant defence of the hippocampus by boosting the activities of SOD, CAT, GPx, and GR. These findings were accompanied by an increased GSH, alongside decreased MDA and NO levels. Furthermore, schizophrenic rats having received PDG and Na2SeO3 displayed markedly lower IL-1ß and TNF-α levels compared to the model group. Interestingly, remarkable declines in the Bax (pro-apoptotic) and increases in Bcl-2 (anti-apoptotic) levels were observed in the SCZ group that received PDG and Na2SeO3. The hippocampal histological examination confirmed these changes. Collectively, these findings show that the co-administration of PDG and Na2SeO3 may have a promising therapeutic effect for SCZ. This is mediated by mechanisms related to the modulation of cholinergic, dopaminergic, and glutaric neurotransmission and neurotrophic factors, alongside the suppression of oxidative damage, neuroinflammation, and apoptosis machinery.

Modulation of inflammatory, oxidative, and apoptotic stresses mediates the renoprotective effect of daidzein against glycerol-induced acute kidney injury in rats.

Acute kidney injury (AKI) is a life-threatening complication that accompanies rhabdomyolysis. Daidzein is a dietary isoflavone that has various biological activities. This study examined the therapeutic potential of daidzein and the underlying mechanisms against AKI induced by glycerol in male rats. Animals were injected once with glycerol (50%, 10 ml/kg, intramuscular) for induction of AKI and pre-treated orally with daidzein (25, 50, and 100 mg/kg) for 2 weeks. Biochemical, histopathological, immunohistopathological, and molecular parameters were assessed to evaluate the effect of daidzein. The results revealed that the model group displayed remarkable functional, molecular, and structural changes in the kidney. However, pre-administration of daidzein markedly decreased the kidney relative weight as well as the levels of urea, creatinine, K, P, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C. Further, daidzein lessened the rhabdomyolysis-related markers [lactate dehydrogenase (LDH) and creatine kinase (CK)]. Notably, the enhancement of the antioxidant biomarkers [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and reduced glutathione (GSH) is accompanied by a decrease in malondialdehyde (MDA) and nitric oxide (NO) levels. Moreover, upregulated gene expression levels of nuclear factor erythroid 2-related factor 2 (Nfe212) and hemeoxygenase-1 (Hmox1) were exerted by daidzein administration. Rats who received daidzein displayed markedly lower interleukin-1ß (IL-1ß), tumor nuclear factor-α (TNF-α), myleoperoxidase (MPO), and nuclear factor kappa B (NF-κB) levels together with higher interleukin-10 (IL-10) related to the model group. Remarkably, significant declines were noticed in the pro-apoptotic (Bax and caspase-3) and rises in antiapoptotic (Bcl-2) levels in the group that received daidzein. The renal histological screening validated the aforementioned biochemical and molecular alterations. Our findings support daidzein as a potential therapeutic approach against AKI-induced renal injury via suppression of muscle degradation, oxidative damage, cytokine release, and apoptosis.

First Report of Isolation and Molecular Characterization of Felid Herpesvirus-1 from Symptomatic Domestic Cats in Egypt.

Feline herpesvirus 1 (FHV-1) is one of the main causes of upper respiratory tract infection in cats. Despite its veterinary importance, no previous studies investigated the occurrence of this virus in Egypt. In the present work, a total number of one hundred forty (N = 140) conjunctival and/or oropharyngeal swabs were collected from symptomatic cats during veterinary clinic visits located in two Egyptian provinces. Virus isolation was performed in the Chorioallantoic membranes (CAMs) of 12-days-old SPF eggs. Interestingly, the embryos showed stunting growth and abnormal feathering and infected CAMs showed edematous thickening and cloudiness with characteristic white opaque pock lesions. Polymerase chain reaction (PCR) amplification of the thymidine kinase gene (TK) was successful in 16/140 (11.4%) of the suspected cases. Two of the amplified genes were sequenced and the TK gene sequences of the FHV-1 isolates were highly similar to other reference strains in the GenBank database. Given the above information, the present study represents the first report of feline herpesvirus type 1 (FHV-1) in domestic cats in Egypt. Further studies on the causes of upper respiratory tract infections in cats as well as vaccine efficacy are needed.

In vitro investigation of the antiviral activity of propolis and chitosan nanoparticles against the genotype VII Newcastle disease virus.

The Newcastle disease virus (NDV) is considered a serious threat to global poultry production. Despite the availability of vaccines, it remains a major devastating epidemic responsible for great economic losses. The development of novel virus-controlling strategies is therefore an urgent need. The present study investigated for the first time the antiviral efficacy of propolis and chitosan nanoparticles against two NDV isolates, MW881875 and MW881876, recovered from vaccinated commercial broiler farms in KafrEl Sheikh Governorate, Egypt. The polygenetic analysis focused on the F and M genes, with one isolate having a 97% identity with the genotype VII NDV Israeli strain. On the other hand, the identified isolates showed high genetic variation and only 76% identity with the LaSota vaccine (genotype II). More interestingly, the cell cytotoxic concentrations of chitosan, propolis, and a propolis-chitosan mixture against Vero cells were 327.41 ± 12.63, 109.48 ± 8.36, and 231.78 ± 11.46 µg/ml, respectively. The median tissue culture infectious dose (TCID50) assay demonstrated that the nanoparticles have antiviral effects after NDV exposure resulting in significant decrease in viral titer (TCID50) by 2, 2.66, and 2.5 log10 at 62 µg/ml of chitosan, 13 µg/ml of propolis, and 30 µg/ml of the propolis-chitosan mixture, respectively, compared with the control TCID50 value of 4 log10. Taken together, the results provide novel insights into the potentially promising roles of propolis and chitosan as novel, safe, and effective antiviral agents against NDV.

Apigenin attenuates molecular, biochemical, and histopathological changes associated with renal impairments induced by gentamicin exposure in rats.

Gentamicin (GM) is an aminoglycoside antibiotic used to treat bacterial infections. However, its application is accompanied by renal impairments. Apigenin is a flavonoid found in many edible plants with potent therapeutic values. This study was designed to elucidate the therapeutic effects of apigenin on GM-induced nephrotoxicity. Animals were injected orally with three different doses of apigenin (5 mg kg-1 day-1, 10 mg kg-1 day-1, and 20 mg kg-1 day-1). Apigenin administration abolished the alterations in the kidney index and serum levels of kidney-specific functions markers, namely blood urea nitrogen and creatinine, and KIM-1, NGAL, and cystatin C following GM exposure. Additionally, apigenin increased levels of enzymatic (glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase) and non-enzymatic antioxidant proteins (reduced glutathione) and decreased levels of lipid peroxide, nitric oxide, and downregulated nitric oxide synthase-2 in the kidney tissue following GM administration. At the molecular scope, apigenin administration was found to upregulate the mRNA expression of Nfe2l2 and Hmox1 in the kidney tissue. Moreover, apigenin administration suppressed renal inflammation and apoptosis by decreasing levels of interleukin-1ß, tumor necrosis factor-alpha, nuclear factor kappa-B, Bax, and caspase-3, while increasing B-cell lymphoma-2 compared with those in GM-administered group. The recorded data suggests that apigenin treatment could be used to alleviate renal impairments associated with GM administration.