SGLT2 inhibitor as a potential therapeutic approach in hyperthyroidism-induced cardiopulmonary injury in rats.

Hyperthyroidism-induced cardiac disease is an evolving health, economic, and social problem affecting well-being. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2-I) have been proven to be cardio-protective when administered in cases of heart failure. This study intended to investigate the potential therapeutic effect of SGLT2-I on hyperthyroidism-related cardiopulmonary injury, targeting the possible underlying mechanisms. The impact of the SGLT2-I, dapagliflozin (DAPA), (1 mg/kg/day, p.o) on LT4 (0.3 mg/kg/day, i.p)-induced cardiopulmonary injury was investigated in rats. The body weight, ECG, and serum hormones were evaluated. Also, redox balance, DNA fragmentation, inflammatory cytokines, and PCR quantification in heart and lung tissues were employed to investigate the effect of DAPA in experimentally induced hyperthyroid rats along with histological and immunohistochemical examination. Coadministration of DAPA with LT4 effectively restored all serum biomarkers to nearly average levels, improved ECG findings, and reinstated the redox balance. Also, DAPA could improve DNA fragmentation, elevate mtTFA, and lessen TNF-α and IGF-1 gene expression in both organs of treated animals. Furthermore, DAPA markedly improved the necro-inflammatory and fibrotic cardiopulmonary histological alterations and reduced the tissue immunohistochemical expression of TNF-α and caspase-3. Although further clinical and deep molecular studies are required before transposing to humans, our study emphasized DAPA's potential to relieve hyperthyroidism-induced cardiopulmonary injury in rats through its antioxidant, anti-inflammatory, and anti-apoptotic effects, as well as via antagonizing the sympathetic over activity.

An animal study on the effectiveness of platelet-rich plasma as a direct pulp capping agent.

Direct pulp capping (DPC) is a conservative approach for preserving tooth vitality without requiring more invasive procedures by enhancing pulp healing and mineralized tissue barrier formation. We investigated the effectiveness of Platelet Rich Plasma (PRP) vs. Mineral Trioxide Aggregate (MTA) as a DPC agent. Forty-two teeth from three mongrel dogs were divided into two equal groups. After three months, the animals were sacrificed to evaluate teeth radiographically using cone-beam computerized tomography, histopathologically, and real-time PCR for dentin sialophosphoprotein (DSPP), matrix extracellular phosphoglycoprotein (MEPE), and nestin (NES) mRNA expression. Radiographically, hard tissue formation was evident in both groups without significant differences (p = 0.440). Histopathologic findings confirmed the dentin bridge formation in both groups; however, such mineralized tissues were homogenous without cellular inclusions in the PRP group, while was osteodentin type in the MTA group. There was no significant difference in dentin bridge thickness between the PRP-capped and MTA-capped teeth (p = 0.732). The PRP group had significantly higher DSPP, MEPE, and NES mRNA gene expression than the MTA group (p < 0.05). In conclusion, PRP enables mineralized tissue formation following DPC similar to MTA, and could generate better cellular dentinogenic responses and restore dentin with homogenous architecture than MTA, making PRP a promising alternative DPC agent.

Potential chemopreventive effects of Broccoli extract supplementation against 7, 12 dimethyl Benz(a)anthracene (DMBA) -induced toxicity in female rats.

Dietary components have recently received rapidly expanding attention for their potential to halt or reverse the development of many oxidative stress-mediated diseases after exposure to environmental toxicants. 7, 12 dimethylbenz(a)anthracene (DMBA) is one of the most common environmental pollutants. The present study aimed to evaluate the chemo-preventive effects of broccoli as a nutritional component against DMBA intoxication in rats. A daily dose of aqueous (1 ml/rat) and methanolic (150 mg/kg) broccoli extracts, respectively, was given to 50-day-old female rats for 26 successive weeks after carcinogen intoxication with a single dose of 20 mg/ml of DMBA. DMBA intoxication resulted in a redox imbalance (a decreased GSH level and an increased MDA level) and increased DNA fragmentation in the liver, kidney, and brain. Besides, it affected the level of expression of the bcl2 gene in the liver, kidney, and brain tissue but didn't affect cfos gene expression accompanied by histopathological changes. The aqueous and methanolic broccoli extract supplements ameliorated the adverse effects by increasing the level of GSH, decreasing the MDA level, and reducing DNA fragmentation. Besides, broccoli extracts decreased the expression of bcl2 in the liver and brain and up-regulated bcl2 expression in the kidney, accompanied by lowering NF-κß 65 expression in the liver and brain and γ-catenin expression in the liver and kidney. In conclusion, broccoli as a dietary component had a strong chemoprotective effect against oxidative stress, DNA damage, and genotoxicity induced by DMBA intoxication in rats.

Neem leaf powder (Azadirachta indica) mitigates oxidative stress and pathological alterations triggered by lead toxicity in Nile tilapia (Oreochromis niloticus).

This study investigated the clinical and pathological symptoms of waterborne lead toxicity in wild Nile tilapia collected from a lead-contaminated area (the Mariotteya Canal: Pb = 0.6 ± 0.21 mg L-1) and a farmed fish after 2 weeks of experimental exposure to lead acetate (5-10 mg L-1) in addition to evaluating the efficacy of neem leaf powder (NLP) treatment in mitigating symptoms of lead toxicity. A total of 150 fish (20 ± 2 g) were alienated into five groups (30 fish/group with three replicates). G1 was assigned as a negative control without any treatments. Groups (2-5) were exposed to lead acetate for 2 weeks at a concentration of 5 mg L-1 (G2 and G3) or 10 mg L-1 (G4 and G5). During the lead exposure period, all groups were reared under the same conditions, while G3 and G5 were treated with 1 g L-1 NLP. Lead toxicity induced DNA fragmentation and lipid peroxidation and decreased the level of glutathione and expression of heme synthesis enzyme delta aminolaevulinic acid dehydratase (ALA-D) in wild tilapia, G2, and G4. NLP could alleviate the oxidative stress stimulated by lead in G3 and showed an insignificant effect in G5. The pathological findings, including epithelial hyperplasia in the gills, edema in the gills and muscles, degeneration and necrosis in the liver and muscle, and leukocytic infiltration in all organs, were directly correlated with lead concentration. Thus, the aqueous application of NLP at 1 g L-1 reduced oxidative stress and lowered the pathological alterations induced by lead toxicity.

Circulating miR-146b and miR-27b are efficient biomarkers for early diagnosis of Equidae osteoarthritis.

One of the most orthopedic problems seen in the equine is osteoarthritis (OA). The present study tracks some biochemical, epigenetic, and transcriptomic factors along different stages of monoiodoacetate (MIA) induced OA in donkeys in serum and synovial fluid. The aim of the study was the detection of sensitive noninvasive early biomarkers. OA was induced by a single intra-articular injection of 25 mg of MIA into the left radiocarpal joint of nine donkeys. Serum and synovial samples were taken at zero-day and different intervals for assessment of total GAGs and CS levels as well as miR-146b, miR-27b, TRAF-6, and COL10A1 gene expression. The results showed that the total GAGs and CS levels increased in different stages of OA. The level of expression of both miR-146b and miR-27b were upregulated as OA progressed and then downregulated at late stages. TRAF-6 gene was upregulated at the late stage while synovial fluid COL10A1 was over-expressed at the early stage of OA and then decreased at the late stages (P < 0.05). In conclusion, both miR-146b and miR-27b together with COL10A1 could be used as promising noninvasive biomarkers for the very early diagnosis of OA.

Histopathological, biochemical and molecular studies on a model of systemic autoimmune disease induced by sodium silicate in non-genetically prone rats.

Sodium silicate (Na2SiO3) is an inorganic silica salt used in many products. Few studies reported autoimmune diseases (AIDs) due to Na2SiO3 exposure. This study investigates the role of Na2SiO3 exposure by different routes and doses in AID development in rats. We assigned 40 female rats to four groups: G1 control group, G2 rats were subcutaneously injected with 5 mg Na2SiO3 suspension, and G3 and G4 rats were orally administered 5 mg and 7 mg Na2SiO3 suspension, respectively. Na2SiO3 was administered weekly for 20 weeks. Serum anti-nuclear antibodies (ANA) detection, histopathology of kidney, brain, lung, liver, and heart, oxidative stress biomarkers (MDA and GSH) in tissues, Matrix metalloproteinase activity in serum, TNF-α, and Bcl-2 expression in tissues were performed. ANA was significantly increased in silicate groups, especially G2. Creatinine was significantly increased in silicate groups. Histopathology revealed vasculitis and fibrinoid degeneration of blood vessels, a picture of immune-mediated glomerulonephritis in the kidneys, and chronic interstitial pneumonia with medial hypertrophy of pulmonary blood vessels. The activity of gelatinases (MMP-2 and MMP-9) and collagenase (MMP-13), which play role in inflammation, remodeling, and immune complex degradation, were significantly increased in the silicate-exposed groups. Bcl-2 was significantly decreased, indicating apoptosis. Therefore, oral administration and subcutaneous injection of Na2SiO3 induced immune-mediated glomerulonephritis with elevated ANA levels and overexpression of TNF-α in rats.

Selenium nanoparticles impart robust neuroprotection against deltamethrin-induced neurotoxicity in male rats by reversing behavioral alterations, oxidative damage, apoptosis, and neuronal loss.

This study investigated the neuroprotective role of selenium nanoparticles (SeNPs) on deltamethrin-induced neurotoxicity in rats. A total of 32 adult male Wister rats were allocated into the following four groups: 1) control, 2) deltamethrin (0.6 mg/kg), 3) SeNPs (0.5 mg/kg), and 4) deltamethrin + SeNPs. All agents were administered orally three times per week for 2 months. Locomotor behavior, anxiety-like behavior, biochemical parameters, including brain oxidative damage biomarkers (Malondialdehyde (MDA) and reduced glutathione (GSH)), brain acetylcholinesterase (AChE), and brain genotoxicity were evaluated. The gene expression levels of IGF-1 and Bcl2 were also determined. Moreover, a brain histopathological examination associated with the immunohistochemical determination of Bax in brain tissue was performed. Deltamethrin-intoxicated rats showed a reduction in the locomotor activity associated with a highly anxious state. They also displayed a disturbance in the brain redox state with a decrease in the brain AChE levels and a high DNA fragmentation percentage. Furthermore, they showed a decrement in the immunohistochemical GFAP levels as well as IGF-1 and Bcl2 gene expression levels with an increase in the immunohistochemical Bax levels. All these changes were confirmed by brain histopathology. Interestingly, SeNPs ameliorated all these changes and restored the normal brain architecture. In conclusion. SeNPs possess a potent medicinal activity due to their antioxidant and anti-inflammatory activity. Therefore, SeNPs can be a potential agent in ameliorating deltamethrin-induced neurotoxicity.

Sesamol protects against aluminum oxide nanoparticles-induced hepatorenal toxicity in rats via modulation of oxidative stress, inflammation, apoptosis, and DNA damage.

Aluminum oxide nanoparticles (Al2 O3 -NPs) are exceedingly used in various industrial and commercial applications, providing growing concerns about their potential adverse impacts on animals and human health. Therefore, the present study was conducted to evaluate the potential protective effect of sesamol (SML) against the induced hepatorenal toxicity of Al2 O3 -NPs. Forty male rats were randomly assigned into four groups and treated orally for 28 consecutive days. Control group received distilled water. SML group received SML (100 mg/kg bw). Al2 O3 -NPs group received Al2 O3 -NPs (100 mg/kg bw). SML + Al2 O3 -NPs group received SML 2 h prior to Al2 O3 -NPs. The results revealed that Al2 O3 -NPs significantly increased serum alanine aminotransferase and aspartate aminotransferase activities and serum urea and creatinine levels. Moreover, Al2 O3 -NPs induced a significant elevation in malondialdehyde level with significant reduction in reduced glutathione content and catalase and superoxide dismutase activities, together with a marked increase of 8-hydroxy-2-desoxyguanosine level in the hepatic and renal tissues. Also, up-regulations of glutathione-S-transferase, tumor necrosis factor-alpha, and caspase-3 mRNA gene expressions were recorded in the liver and kidneys. Additionally, Al2 O3 -NPs induced multifocal areas of necrosis in hepatic parenchyma with glomerular mesangial cell proliferation and glomerular sclerosis in kidney tissues. Conversely, concomitant treatment with sesamol mitigated Al2 O3 -induced hepatorenal toxicity evidenced by improvement of liver and kidney functions that correlated with regulation of oxidant/antioxidant status, inflammatory, and apoptotic biomarkers and reduction of DNA and tissues damages. In conclusion, sesamol could exert a promising protective role against hepatorenal toxicity of Al2 O3 -NPs, possibly via its antioxidant, anti-inflammatory and anti-apoptotic properties.

The efficiency of intrauterine infusion of platelet-rich plasma in the treatment of acute endometritis as assessed by endoscopic, Doppler, oxidative, immunohistochemical, and gene expression alterations in jennies.

This study used autologous platelet-rich plasma (PRP) to treat acute endometritis in jennies with follow-up for alterations in uterine hemodynamics, endoscopic, immunohistochemistry, oxidant/antioxidant imbalance, pro-inflammatory regulatory molecules, and transmembrane mucin expressions. Ten jennies suffering from endometritis (acute type; n = 10) were included in the study. PRP was prepared from each animal and two intrauterine infusions one week apart were administrated. Examination and follow-up were done physically, ultrasonographically, endoscopically and samples were taken for histopathology, immunohistochemistry, and bacteriological examination. Blood and uterine fluid samples were taken to estimate biochemical and oxidative stress alterations. Expression of TRAF6 and MUC1 genes was investigated in uterine fluid, at days -1 (day of diagnosis establishment), 7, 14, and 21. Uterine bacteriological examination showed a decrease in bacterial isolates after PRP treatment. The uterine thickness and uterine vascular perfusion as illustrated by color Doppler ultrasonography were significantly decreased in jennies treated by PRP. Uterine spectral wave pattern showed a significant linear increase in pulsatility index only. Three weeks after first PRP treatment, white light endoscopic examination revealed normal uterine body mucosa and uterine horn folds. A high nuclear factor (NF-κB) expression was seen in the mononuclear cells. A significant reduction in oxidative stress biomarkers in both serum and uterine fluid was recorded after PRP treatment. The TRAF-1 gene expression significantly decreased gradually after intrauterine PRP infusion. The MUC-1 gene expression significantly decreased gradually after intrauterine PRP infusion. Both genes were within normal levels by week 3. Endometritis in jennies is associated with an oxidative process, alterations in serum biochemical parameters, Doppler indices, endoscopic appearance, high NF-κB expression, and upregulation of TRAF-1 and MUC-1 expressions. Two intrauterine infusions of autologous PRP restored normal endometrial appearance after acute endometritis.

Histopathological, Immunohistochemical, And Molecular Alterations In Brain Tissue And Submandibular Salivary Gland Of Atrazine-Induced Toxicity In Male Rats.

Atrazine (ATZ) is herbicide that has been widely used for different crops. This extensive use has resulted in severe deleterious effects in different species. In this work, we investigated the potentially harmful effect of atrazine herbicide on the brain and submandibular salivary gland. Our investigation was carried out on 20 adult male albino rats that were equally divided into two groups. The first group received distilled water as control, while the second group received ATZ at 200 mg/kg body weight/ day via stomach gavage for 30 successive days of the experiment; the oral LD50 for ATZ is 3090 mg/kg. Our findings revealed the ability of ATZ to cause damage to the cerebrum, hippocampus, and submandibular salivary gland. This damage resulted from the induced oxidative stress, which was indicated by a significant elevation in malondialdehyde (MDA) concentration, DNA fragmentation, tumor necrotic factor-alpha (TNF-α) expression, with a significant decrease in reduced glutathione (GSH) level and reduction of B cell lymphoma 2 (BCL2), dopamine receptor D1 (Drd1), cAMP-responsive element-binding protein 1 (Creb1) genes expression after ATZ exposure. Moreover, degeneration of cells, cytoplasmic vacuolation, congestion of blood vessels, a strong immune reaction to caspase 3, and negligible immune expression of a glial fibrillary acidic protein (GFAP) were also noticed in the ATZ-treated group. We concluded that ATZ induces oxidative stress and has a toxic and apoptotic effects on the cerebrum, hippocampus, and salivary gland of adult male albino rats.

Oxidative stress, apoptosis and histopathological alterations in brain stem and diencephalon induced by subacute exposure to fipronil in albino rats.

Fipronil (FIP) is a highly effective insecticide that has been used in agriculture and veterinary medicine. Its neurotoxic effect to insects and to non-target organisms, after nonintentional exposure, was reported. Many studies were conducted to evaluate FIP effects on mammals. However, slight is known about its effect on the brain stem and diencephalon. The current study was designed to investigate the ability of FIP to induce oxidative stress as a molecular mechanism of FIP neurotoxicity that resulted in apoptosis and neural tissue reactivity in these regions. Ten adult male rats received 10 mg/kg of FIP technical grade by oral gavage, daily for 45 days. Brain stem and diencephalon were processed to examine oxidative stress-induced macromolecular alteration (MDA, PCC and DNA fragmentation). Also, the histopathological assessment and immunoreactivity for caspase-3 (active form), iNOS and GFAP were performed on the thalamus, hypothalamus and medulla oblongata. Our results revealed that FIP significantly raised MDA, PCC and DNA fragmentation (p ≤ 0.05). In addition, significantly increased immunoreactivity to GFAP, iNOS and caspase-3 (active form) in the FIP-treated group was noticed (p ≤ 0.05). Moreover, alterations in the histoarchitecture of the neural tissue of these regions were observed. We conclude that FIP can induce oxidative stress, leading to apoptosis and tissue reaction in brain stem and diencephalon.

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

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

Fipronil induced oxidative stress in neural tissue of albino rat with subsequent apoptosis and tissue reactivity.

Fipronil (FIP) insecticide is extensively used in agriculture, public health and veterinary medicine. Although it is considered as a neurotoxin to insects (target organisms) and exhibits neurological signs upon vertebrates (non-target organisms) exposure, slight is known about its potential neurotoxic effects and its molecular mechanisms on vertebrates. The current study is designed to assess oxidative stress as a molecular mechanism of FIP neurotoxicity subordinated with apoptosis and neural tissue reactivity. Ten adult male albino rats received 10 mg/kg body weight fipronil technical grade by oral gavage daily for 45 days (subacute exposure). Brain neural tissue regions (hippocampus, cerebellum and caudate putamen) were processed to examine oxidative stress induced cellular macromolecular alterations as MDA, PCC and DNA fragmentation. Besides, TNF-α and Bcl-2 gene expression and immunoreactivity for caspase-3 (active form), iNOS and GFAP were evaluated. Also, histopathological assessment was conducted. We found that FIP significantly raised MDA, PCC and DNA fragmentation (p ≤ 0.05). Also, it significantly upregulated TNF-α and non-significantly down-regulated Bcl-2 gene expression (p ≤ 0.05). Further, significant increased immunoreactivity to GFAP, iNOS and caspase-3 (active form) in these brain neural tissue regions in FIP treated group was noticed (p ≤ 0.05). Histopathological findings, including alterations in the histological architecture and neuronal degeneration, were also observed in these brain regions of FIP treated group. In conclusion, we suggest the ability of FIP to induce oxidative stress mediated macromolecular alterations, leading to apoptosis and tissue reaction in these brain regions which showed variable susceptibility to FIP toxic effects.

Intra-iliac bone marrow injection as a novel alternative to intra-tibial inoculation in rat model.

BACKGROUND: Intra-bone marrow injection (IBMI) in rats is adopted in many studies for stem cell and hematopoietic cell transplantation. IBMI in the tibia or the femur results in severe distress to the animal. Therefore, this study aims to evaluate intra-iliac injections as an alternative approach for IBMI. METHODS: Twenty-seven Sprague Dawley rats were assigned into 3 groups, 9 rats each, for 4 weeks. The control group rats were not injected. Tibia group rats were injected intra-tibial and the iliac group rats were injected intra-iliac with saline. Behavioral, radiological, histopathological, and stress evaluation was performed. Total bilirubin, cortisol, and insulin-like growth factor-1 (IGF1) were measured. RESULTS: Behavioral measurements revealed deviation compared to control, in both injected groups, on the 1st and 2nd week. By the 3rd week, it was equivalent to control in the iliac group only. Bilirubin and cortisol levels were increased by intra-tibial injection compared to intra-iliac injection. The IGF-1 gene expression increased compared to control at 1st and 2nd weeks in intra-iliac injection and decreased by intra-tibial injection at 2nd week. The thickness of the iliac crest was not different from the control group, whereas there were significant differences between the control and tibia groups. Healing of the iliac crest was faster compared to the tibia. In the 3rd week, the tibia showed fibrosis at the site of injection whereas the iliac crest showed complete bone reconstruction. CONCLUSION: Intra-iliac injections exert less distress on animals, and by 3 weeks, they regained their normal activity in comparison to intra-tibial injections.

Neuroprotective effect of sesamol against aluminum nanoparticle-induced toxicity in rats.

Alumina nanoparticles (ALNPs) are widely used causing neurobehavioral impairment in intoxicated animals and humans. Sesamol (SML) emerged as a natural phytochemical with potent antioxidant and anti-inflammatory properties. However, no study has directly tested the potential of SML to protect against AlNP-induced detrimental effects on the brain. AlNPs (100 mg/kg) were orally administered to rats by gavage with or without oral sesamol (100 mg/kg) for 28 days. In AlNP-intoxicated group, the brain AChE activity was elevated. The concentrations of MDA and 8-OHdG were increased suggesting lipid peroxidation and oxidative DNA damage. GSH depletion with inhibited activities of CAT and SOD were demonstrated. Serum levels of IL-1ß and IL-6 were elevated. The expressions of GST, TNF-α, and caspase-3 genes in the brain were upregulated. Histopathologically, AlNPs induced hemorrhages, edema, neuronal necrosis, and/or apoptosis in medulla oblongata. The cerebellum showed loss of Purkinje cells, and the cerebrum showed perivascular edema, neuronal degeneration, necrosis, and neuronal apoptosis. However, concomitant administration of SML with AlNPs significantly ameliorated the toxic effects on the brain, reflecting antioxidant, anti-inflammatory, and anti-apoptotic effects of SML. Considering these results, sesamol could be a promising phytochemical with neuroprotective activity against AlNP-induced neurotoxicity.

Corneal Ulcer in Dogs and Cats: Novel Clinical Application of Regenerative Therapy Using Subconjunctival Injection of Autologous Platelet-Rich Plasma.

Background: Corneal ulcer could be a major source of distress in small animals, with many contributing agents. In recent years, few studies evaluated the efficacy of platelet-rich plasma (PRP) in healing corneal ulcers. Aim: This study aimed to assess the ability of subconjunctival injection of autologous PRP in the treatment of corneal ulcers in dogs and cats as well as estimate the expression of matrix metalloproteinase (MMP)-2, MMP-9, and oxidative stress biomarkers in these patients. Methods: A total number of 28 animals (16 cats and 12 dogs) were enrolled in this study. Each animal was subjected to clinical, neurologic, and ophthalmic examinations where the type of ulcer was documented. Tear samples were collected for evaluation of oxidative biomarkers and MMPs; conjunctival swabs were taken to identify the involved organism. PRP was prepared from each animal and given as subconjunctival injection; numbers of injections were done according to case response. Clinical follow-up was done and documented for each case. Results: In cat patients, female and Persian cats were most affected; unilateral and superficial ulcers were most recorded. In male dogs, unilateral, and superficial ulcers were most recorded. FHV-1 was most identified in cats, while Staphylococcus aureus was most identified in dogs. Numbers of injections needed to achieve healing were recorded, with 50% of dogs needing two injections with 1-week intervals and 50% of cats needed three injections with 1-week intervals. Alterations in both oxidative biomarkers and MMPs were recorded in affected animals. Conclusion: The use of autologous PRP as a subconjunctival injection in treating corneal ulcers in dogs and cats is effective. The number of injections is the case and corneal ulcer type-dependent. Clinical Significance: Autologous PRP as a subconjunctival injection in treating corneal ulcer is a relatively cheap, safe method and can be done in the clinical setting.

Epidemiological and genetic characteristics of asymptomatic canine leishmaniasis and implications for human Leishmania infections in Egypt.

Leishmaniasis is a neglected zoonotic disease that poses significant veterinary and public health risks in developing countries. Dogs act as a reservoir host for leishmaniasis transmitted to humans. A total of 108 human cases of cutaneous leishmaniasis (CL) were identified in the Al-Houd Al-Marsoud Hospital in Cairo, Egypt, during 2018. Blood samples and skin biopsies were collected for further examination. Blood samples from 96 asymptomatic dogs were collected. All samples were subjected to molecular and phylogenetic analysis. Quantitative RT-PCR was used to measure the expression of genes related to mTOR signalling and inflammation in blood and tissue samples. The distribution pattern of human cases pointed to an endemic focus in North Sinai (66.67%). The prevalence of asymptomatic canine leishmaniasis was 66.60%. Histopathological examination of human skin lesions revealed a severe granulomatous inflammatory reaction, necrosis and ulceration. Moreover, leishmanial amastigotes could be detected in human tissue samples. Phylogenetic analysis revealed 100% identity of human isolates to Leishmania tropica (MN453682), and dog isolates to Leishmania infantum (MN453673), with 94.9% similarity between the two isolates. Gene expression related to mTOR signalling and inflammation in both species' samples confirmed a significant alteration of EIF4EBP1, CCR4 and INF-γ expression compared with control groups. In Egypt, increased incidence of asymptomatic carrier dogs acting as a significant reservoir host for Leishmania poses a public health hazard. Findings warrant further epidemiological investigation of CL in Egypt, as well as additional study of parasite differentiation and gene regulation.

Ameliorative effects of jojoba oil on fipronil-induced hepatorenal- and neuro-toxicity: the antioxidant status and apoptotic markers expression in rats.

Jojoba (Simmondsia chinensis) is an economically important plant due to its high oil content in the seeds. Fipronil is an extensively used phenylpyrazole insecticide. The present investigation aimed to assess the possible ameliorative effect of jojoba oil on fipronil induced toxicity in rats. Animals orally received the insecticide dissolved in corn oil by stomach tube at 1/10th LD50 for 28 days. Fipronil induced hepatorenal toxic effects evidenced by elevated serum ALT, AST, ALP, and LDH activities, and urea and creatinine levels, with histomorphological changes in the liver and kidney. Brain GABA was elevated with histopathological alterations in the brain tissue. Oxidative stress was demonstrated in liver, brain, and kidney as indicated by elevated MDA and NO levels with reduction in GSH level and activities of SOD and CAT. In addition, caspase-3 gene expression was enhanced, while Bcl2 gene expression was downregulated in the three organs. Increased DNA fragmentation was recorded in the liver and kidney. Cotreatment of jojoba oil with fipronil ameliorated the toxic effects of fipronil on various organs with improvement of the antioxidant status, the rate of apoptosis and the histopathological alterations. In conclusion, jojoba oil provided significant protection against fipronil induced hepatorenal- and neuro-toxicity, by its antioxidant and antiapoptic effects, making it a possible beneficial protective of natural origin.

COL2A1 and Caspase-3 as Promising Biomarkers for Osteoarthritis Prognosis in an Equus asinus Model.

Osteoarthritis (OA) is one of the most degenerative joint diseases in both human and veterinary medicine. The objective of the present study was the early diagnosis of OA in donkeys using a reliable grading of the disease based on clinical, chemical, and molecular alterations. OA was induced by intra-articular injection of 25 mg monoiodoacetate (MIA) as a single dose into the left radiocarpal joint of nine donkeys. Animals were clinically evaluated through the assessment of lameness score, radiographic, and ultrasonographic findings for seven months. Synovial fluid and cartilage samples were collected from both normal and diseased joints for the assessment of matrix metalloproteinases (MMPs) activity, COL2A1 protein expression level, and histopathological and immunohistochemical analysis of Caspase-3. Animals showed the highest lameness score post-induction after one week then decreased gradually with the progression of radiographical and ultrasonographic changes. MMP activity and COL2A1 and Caspase-3 expression increased, accompanied by articular cartilage degeneration and loss of proteoglycan. OA was successfully graded in Egyptian donkeys, with the promising use of COL2A1and Caspase-3 for prognosis. However, MMPs failed to discriminate between early and late grades of OA.