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5-fluorouracil (5-FU) is a widely used chemotherapeutic drug, but its hepatotoxicity challenges its clinical use. Thus, searching for a hepatoprotective agent is highly required to prevent the accompanied hepatic hazards. The current study aimed to investigate the potential benefit and mechanisms of action of rupatadine (RU), a Platelet-activating factor (PAF) antagonist, in the prevention of 5-FU-related hepatotoxicity in rats. Hepatotoxicity was developed in male albino rats by a single 5-FU (150 mg/kg) intra-peritoneal injection on the 7th day of the experiment. RU (3 mg/kg/day) was orally administrated to the rodents for 10 days. Hepatic toxicity was assessed by measuring both liver and body weights, serum alanine aminotransferase and aspartate aminotransferase (ALT and AST), hepatic oxidative stress parameters (malondialdehyde (MDA), nitric oxide levels (NOx), reduced glutathione (GSH), superoxide dismutase (SOD)), and heme oxygenase-1 (HO-1). Inflammatory markers expressions (inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNFα), interleukins; IL-1B, IL-6), the apoptotic marker (caspase-3), and PAF were measured in the hepatic tissue. 5-FU-induced hepatotoxicity was proved by the biochemical along with histopathological assessments. RU ameliorated 5-FU-induced liver damage as proved by the improved serum ALT, AST, and hepatic oxidative stress parameters, the attenuated expression of hepatic pro-inflammatory cytokines and PAF, and the up-regulation of HO-1. Therefore, it can be concluded that RU pretreatment exerted a hepatoprotective effect against 5-FU-induced liver damage through both its powerful anti-inflammatory, antioxidant, and anti-apoptotic effect.

Acrylamide (ACR) is selective neurotoxicity, could be found in foods processed by high temperature. This work aimed to evaluate the protective role of the dark chocolate (DC) against cerebellar neurotoxicity induced by subchronic ACR exposure in recently weaned rat pups and to propose it as protective supplement against dietary ACR hazards. Eighteen weaning pups were used in the current study and divided into three groups, six rats in each group; group 1 (control group), group 2 (ACR group), and group 3 (ACR + DC group). The pups were sacrificed after 21 days and the cerebellums were removed for light microscope using H&E stain, ultrastructural study, morphometric analysis of the neurons count, biochemical analysis of oxidant and antioxidant markers and real-time quantitative PCR to evaluate the nuclear receptor subfamily 4, group A, member 2 (Nr4a2) gene expression. Pups with ACR consumption showed signs of neuronal degeneration and reduced Nr4a2 expression. On the other hand, pups with ACR + DC consumption showed relative signs of neuronal restoration and enhanced Nr4a2 expression. In conclusion, DC can be used as effective supplement to decrease the dietary ACR cerebellar neuronal risks.

Testicular torsion is an emergency, mainly in newborn and adolescent males, resulting in testicular ischemia. The current study aimed to evaluate the effect of Idebenone (IDE) on testicular torsion/detorsion (T/D) in juvenile rats. Thirty-two rats were randomized into: (1) the sham group: rats received sham operations with no other interventions; (2) the IDE group: rats received idebenone (100 mg/kg, i. p) without T/D; (3) the T/D group: rats underwent torsion for 2 h and detorsion for 4 h; and (4) the IDE+ T/D group: rats received IDE 1 h before T/D. Testicular malondialdehyde (MDA), total nitrite/nitrate (NOx), total antioxidant capacity (TAC), tumor necrosis factor-α (TNF-α), caspase-3, sirtuin type 1 (Sirt1), serum interleukin-1β (IL-1β), total cholesterol, and testosterone were measured. Histological changes, nuclear factor (erythroid-derived 2)-like-2 factors (Nrf2), and proliferating cell nuclear antigen (PCNA) immuno-expressions were assessed. T/D displayed an increase in MDA, NOx, TNF-α, caspase-3, IL-1β, and total cholesterol with a significant decrease in TAC, Sirt1, and testosterone and strong positive Nrf2 and negative PCNA immuno-expressions. IDE could improve all oxidative, inflammatory, and apoptotic indicators. Therefore, IDE significantly reduced testicular ischemia-reperfusion injury in the juvenile rat testicular T/D model by limiting oxidative stress, inflammation, and apoptosis via the Sirt1/Nrf2/TNF-α pathway.

The increased use of indomethacin (IND) is associated with gastrointestinal injury. This research aims to investigate the effects of a beta-blocker, carvedilol (CAR) on a rat model of IND-induced acute intestinal damage and clarify the probable underlying protective mechanisms.Twenty-four male Wistar rats were divided into four groups. Control group: given vehicles; CAR-treated group: given 10 mg/kg/day CAR PO daily by gastric gavage for 10 consecutive days; IND-treated group: given a single Sc dose of 10 mg/kg IND at the end of the ninth day of the experiment; combined CAR/IND-treated group: given both IND and CAR.In the rats that received IND, severe intestinal histopathological changes together with oxidative and nitrosative intestinal stress were present biochemically and immunohistochemically. Obvious inflammatory and tissue damage were represented by the significant intestinal increases in TNF-α, COX-2, and caspase-3 together with the elevated expression of VCAM-1 adhesion molecules. Intestinal gene expression of NF-kB and COX-2 was also increased. Pretreatment with CAR significantly reversed the IND-induced intestinal toxic manifestations.CAR has beneficial intestinal protective effects. Its ameliorative action is conferred through its antioxidant, antinitrosative, anti-inflammatory, and antiapoptotic properties.

Recent biochemical, metabolic, and molecular profiles of various body fluids showed more accurate correlation to the postmortem interval than the traditional physical examination. Our study aimed to evaluate time passed since death in relation to oxidative stress markers, HMGB1 genetic expression, histopathological examination, and BCL2 immunohistochemical analysis in major organs (heart, kidney, and testis). Forty-two adult male rats were included and randomly divided into seven equal groups. After sacrification, the rodents were kept at room temperature and major organs were obtained at 0, 12, 24, 48, 72, 96, and 120 h. Malonaldehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH) tissue levels, High mobility group box 1 protein (HMGB1) gene expression, histopathological, and B cell lymphoma 2 (BCL2) immunohistochemical expressions were analyzed. Postmortem interval was correlated to different tissue levels of MDA, SOD, and GSH. HMGB1 showed enhanced postmortem gene expression with a peak at 48 h after death. Obvious time-dependent histopathological changes were observed in all the examined organs. Dilated spaces, extravasation, and fragmentation scores in heart specimens were higher at 96 and 120 h compared with the other groups. Renal changes in the form of shrunken glomeruli, loss of tubular epithelium, and hyalinization and testicular findings in the form of epithelial detachment, vacuolation, and loss of sperms started at 72 h postmortem. BCL2 expression began to decrease 24 h and became negative at 96 h after death. In conclusion, HMGB1 gene expression can be used for estimation of time passed since death as it shows time-dependent changes in the form of a progressive increase with a peak at 48 h then it begins to decline. Oxidants and antioxidants are correlated to PMI until 120 h after death. Histopathological changes in the heart, kidney, and testis are also time-dependent until the 5th day after death. BCL2 immunohistochemical expression begins to decline 24 h until 96 h after death when it becomes negative.

The current study aimed to investigate the potential ameliorative role of Rivastigmine (RIVA), the anti-Alzheimer drug, against the gastric mucosal injury caused by indomethacin (IND). The rats were divided into four groups: group I was given a vehicle as a control, group II was given RIVA (0.3 mg/kg) once daily intraperitoneal (ip) for 2 weeks, group III was given a single IP dose of 30 mg/kg IND, and group IV was given RIVA ip 2 weeks before the administration of IND. The gastric mucosal injury was detected by the estimation of ulcer index, gastric acidity, pepsin, and mucin concentrations. Malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), total nitrite/nitrate (NOx), and the expression of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), nuclear factor kappa B (NF-κB), Hemoxygenase 1 (HO-1), and caspase-3 were all measured in gastric tissue. In addition, histological assessment and proliferating cell nuclear antigen (PCNA) immuno-expression were studied. Gastric mucosal injury induced by IND was indicated by both biochemical and histopathological assessments. RIVA Pretreatment reduced ulcer index, MDA, TNF-α, IL-6, NF-κB, and caspase-3 and increased SOD, GSH, NOx, and HO-1. RIVA improved the suppressed nuclear immunoreaction for PCNA observed with IND. The current findings provide novel evidence that RIVA possesses a prophylactic action against IND-induced gastric mucosal damage in rats. Despite being a cholinergic drug that is associated with increased pepsin and stomach acidity, RIVA protected against IND-induced gastric mucosal injury via activating α7nAChR and inhibiting oxidative stress and apoptosis.

Doxorubicin (DOX) is an anticancer agent for treating solid and soft tissue malignancies. However, the clinical use of DOX is restricted by cumulative, dose-dependent cardiotoxicity. Therefore, the present study aimed to assess the cardioprotective effects of

Uterine ischemia is a common problem with ongoing controversy about its pathogenesis and prevention. The present study aimed to investigate the protective role of sitagliptin against uterine ischemia-reperfusion injury (IRI).Rats were allocated into 4 groups: control, sitagliptin (SIT) (5 mg/kg), IR; ischemia was induced followed by reperfusion, and IR+SIT; SIT was administered 1 hr before IRI. Uteri were removed for histopathological and biochemical observations. Malondialdehyde (MDA), total nitrites (NOx), reduced glutathione (GSH), superoxide dismutase (SOD) activity, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and toll-like receptor 4 (TLR4) were all measured. Hematoxylin and eosin (HE) stain, Periodic acid-Schiff stain (PAS), and caspase-3 immunostaining were applied.In the IR+SIT group; NOx, GSH, and SOD activities increased significantly. Meanwhile, the levels of MDA, TNF-α, IL-6, TLR4, and caspase-3 immunoexpression showed a significant reduction, as compared with the IR group. In the IR+SIT group, an improvement in the histopathological picture was noticed.The results showed that sitagliptin confers protection against uterine IRI through anti-oxidant, anti-inflammatory, and anti-apoptotic effects with a possible role for TLR4.

The widespread use of acetaminophen (APAP) in children as an over-the-counter treatment can cause acute liver failure through accidental overdose or ingestion. Therefore, the current research sought to investigate the function of hemin in mitigating the acute hepatotoxic effect of APAP in rat offspring. Thirty-two rats were assigned into four groups: control, hemin, APAP, and hemin/APAP groups. Liver enzymes were measured in serum along with oxidative stress indicators, tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1β), total nitrites (NOx), and caspase 3 in liver. Immunoblotting of heme oxygenase-1 (HO-1), interleukin-6 (IL-6), Janus kinase 2 (Jak2), and signal transducer and activator of transcription 3 (STAT3) was carried out. The Bax/Bcl2 mRNA expression ratio was determined. A histological study and an immunohistochemical study of phosphorylated STAT3 were also done. Hemin reduced liver enzymes, MDA, TNF-α, NOx, caspase 3, IL-1β, p-STAT3 expression, p-Jak2 expression, IL-6 expression, and Bax/Bcl2 mRNA expression ratio. In contrast, hemin increased GSH, TAC, and the expression of HO-1, improving the histopathological picture of liver tissue. Thus, hemin could ameliorate APAP-induced hepatic toxicity in rat offspring through anti-oxidant, anti-apoptotic, and anti-inflammatory actions with a possible role for the IL-6/HO-1/Jak2/STAT3 pathway.

The current experiment aimed to identify the possible protective role of rivastigmine (RIVA) in gentamicin (GNT)-induced acute kidney injury (AKI) in rats. RIVA was administered in the presence and absence of GNT. Kidney function markers and serum and renal GNT concentrations were measured. Renal oxidative stress parameters as well as inflammatory and apoptotic biomarkers were evaluated. Renal histopathological assessment and nuclear factor kappa-B (NF-κB) immunohistochemical study were performed. GNT administration increased serum creatinine, urea, and cystatin C concentrations. RIVA ameliorated these changes via mitigating GNT-induced increases of renal oxidative stress, inflammation, and apoptotic parameters. RIVA showed a prompt improvement in the histopathological renal damage and a decrease in NF-κB immunoexpression. In conclusion, RIVA protective effects against GNT-induced AKI are mediated by decreasing GNT concentration in renal tissue and other effects like antioxidant and antiapoptotic effects possibly through its cholinergic anti-inflammatory action.

Polycystic ovary syndrome (PCOS) is the most common gynaecological endocrine disease that causes anovulatory infertility. The current study aimed to explore the possible role of diacerein (DIA), an IL-1β inhibitor, in treating letrozole-induced PCOS in rats that exhibit the metabolic and endocrinal criteria of PCOS patients. PCOS was induced in female Wistar rats by the oral administration of letrozole (1 mg/kg, per orally, p.o.) for 21 days. Rats were then treated with DIA (25 mg/kg/day, p.o.), DIA (50 mg/kg/day, p.o.), or metformin (2 mg/100 g/day, p.o.) for 14 days after the PCOS induction. PCOS resulted in a significantly higher body weight, ovarian weight, ovarian size, and cysts, as well as an elevation in serum testosterone, LH, insulin, glycemia, and lipid profile levels. All of these effects were significantly reduced by the DIA administration. Additionally, DIA remarkably inhibited the letrozole-induced oxidative stress in the ovaries, muscles, and liver by reducing the upraised levels of malondialdehyde and total nitrite and increasing the suppressed levels of superoxide dismutase and catalase. DIA enhanced the protective proteins Keap-1, Nrf2, and OH-1 levels. Finally, DIA inhibited the elevated mRNA levels of NLRP3 and caspase-1, the up-regulated inflammatory cytokines IL-6, TNF-α, and the IL-1β/NFκB signaling pathway. Our results proved that DIA ameliorates letrozole-induced PCOS through its antioxidant and anti-inflammatory properties.

Background Methotrexate (MTX), an anticancer drug, has been linked to multiple organ toxicity. The drug-induced acute toxic symptoms can negatively affect the patient's commitment to the course of treatment. Materials and methods This study aimed to investigate the mitigating action of agomelatine (Ago) against MTX-induced lung and intestinal toxicity. Forty eight male Wister rats were randomized into six experimental groups: Group 1: Control; Groups 2 and 3: received Ago LH Group 4: received MTX 10 mg/kg/day, i.p. on days 7-9; Group 5: received Ago L (20 mg/kg) + MTX; Group 6: received Ago H (40 mg/kg) +MTX. The duration of the study was 10 days. Lung/intestine oxidative markers were measured. Lung/intestinal tissues IL-6, STAT3, and HO-1 levels were evaluated by ELISA. Besides, lung/intestinal tissues were examined for Histological changes, collagen fibers detection using Massonꞌs trichome stain, and immunohistochemical study using HSP70 antibody. Results MDA, NOx, IL-6, and STAT3 levels were significantly higher in the MTX group's lungs and intestines, indicating lung and intestinal toxicity. There were substantial decreases in GSH, SOD tissue levels, and HSP 70 immunoexpression, as well as histological changes suggesting significant lung and intestinal injury. All of the above parameters improved significantly by using Ago. Conclusion By reducing oxidative stress, inflammatory processes, and modulating the IL-6/STAT3 pathway, Ago has potent ameliorative effects against MTX-induced lung/intestinal toxicities.

Acrylamide (ACR) is selective neurotoxicity, could be found in foods processed by high temperature. This work aimed to evaluate the protective role of the dark chocolate (DC) against cerebellar neurotoxicity induced by subchronic ACR exposure in recently weaned rat pups and to propose it as protective supplement against dietary ACR hazards. Eighteen weaning pups were used in the current study and divided into three groups, six rats in each group; group 1 (control group), group 2 (ACR group), and group 3 (ACR + DC group). The pups were sacrificed after 21 days and the cerebellums were removed for light microscope using HE stain, ultrastructural study, morphometric analysis of the neurons count, biochemical analysis of oxidant and antioxidant markers and real-time quantitative PCR to evaluate the nuclear receptor subfamily 4, group A, member 2 (Nr4a2) gene expression. Pups with ACR consumption showed signs of neuronal degeneration and reduced Nr4a2 expression. On the other hand, pups with ACR + DC consumption showed relative signs of neuronal restoration and enhanced Nr4a2 expression. In conclusion, DC can be used as effective supplement to decrease the dietary ACR cerebellar neuronal risks.

BackgroundDomestic violence is a common problem that is related to many serious short-term and long-term health hazards around the world.MethodsDuring obtaining the medical history from the participants, the questions used to assess the abuse were derived from the widely used Abuse Assessment Screen (AAS). Potential risk factors including a variety of socio-demographic and reproductive health-relation indicators were assessed. The influence of violence on the pregnancy outcome was determined by the continuous follow-up till giving birth.Results513 pregnant women were included. The prevalence of violence among them was 50.8%. The prevalence of physical, sexual, verbal, and emotional abuse was 30.2, 20, 41.7, and 45.4% respectively. Exposure to violence during pregnancy had significant effects on the women and their pregnancy outcome in the form of development of vaginal infection (P-value =0.036), vaginal bleeding (P-value = 0.008), preterm labour (P-value = 0.003), premature rupture of membrane (P-value = 0.001).ConclusionViolence against pregnant women in Minia Governorate, Egypt is common especially emotional violence and it has many adverse effects on the women and their pregnancy outcome. One of the most important risk factors is the fear of the husband which makes violence a continuous vicious circle.

Background Child abuse is a worldwide phenomenon that can cause intense long-term aftereffects. Aim To evaluate the awareness of Beni Suef University students about different forms of child abuse as well as the size, causes, and complications of this problem in our society and determine the prevalence of physical child abuse. Methods The study included 1688 students from health science and non-health science colleges of Beni Suef University, Egypt. The study participants were asked to answer a questionnaire of two parts. The first part included questions about demographic data and personal experience of child abuse, and the second part included questions about opinions of participants on child abuse to assess their awareness and if there was any difference in the level of awareness between students of health science colleges and those of non-health science colleges. Results Health science college students were more life satisfied and felt more loved. Only 28.91% of the included students were not exposed to child abuse, while 12.59% of them suffered from wounds or fractures as a result of the abuse they were exposed to. About one third of the students thought that the commonest form of child abuse is verbal punishment such as threatening or humiliation and that the age at the greatest risk for abuse was the primary school age. About 68.36% of students thought that sexual abuse is a huge problem in our society. Only 21.56% of students disapproved child corporal punishment. More than half of the students stated that the most dangerous complication of child abuse is psychological problems such as depression. Most of the included students would talk to the child’s parents and advise them if they saw a case of abuse, while the least would call the police. Only half of the students disapproved female genital mutilation (FGM). The strongest predictive factors for FGM approval were rural residence and male sex. Students mainly thought that FGM is a social habit that is carried out for ethical causes. About half of the students approved legal punishment by the court for FGM performers. Conclusion A significant proportion of the students experienced physical child abuse which left no injuries in most cases; males and first academic year students show more exposure to abuse. Moreover, most of the students think that child corporal punishment can be allowed although about half of them think that the most dangerous aftereffect of child abuse is psychological problems. Lack of reporting the exposure to child abuse is explained by the largest percentage of students to be due to lack of awareness. Rural resident males show more approval of female genital mutilation. A significant lack of awareness about FGM complications is observed in both groups (the health science and non-health science college groups) and the opinions of both groups are very close.

Epiphyseal plates union gives valuable information about age. The knee joint is an articulation of three long bones so it is an important anatomical site to be considered and it can help for assessment of the age group of 10–20 years particularly. Also the knee can carry important information for sex identification through measuring the femur bicondylar distance and various patellar dimensions. The aim of this study is to assess the value of radiographic knee examination for estimation of age and sex in Egyptian population. Age identification is studied in correlation to the epiphyseal union of distal end of femur, proximal end of tibia, proximal end of fibula and the total score of the knee joint (SKJ). Sex identification is studied in relation to the femur bicondylar distance, patellar breadth, length, depth and volume. Our study included a random sample of 146 knee radiographs from patients who visited Beni Suef university hospital radiology center for diagnostic causes. All the subjects from both sexes aged from 10 to 20 years. Results showed that SKJ has the best correlation to age in comparison to each individual bone score alone for both male (r = 0.92) and female (r = 0.89) subjects with accuracy of 58%. Females showed earlier growth that is statistically insignificant. The femur bicondylar distance showed statistically significant sexual dimorphism with a mean value of 73.92 mm in males and 65.68 mm in females, accuracy is 79.4%. But the patellar sexual differences are statistically insignificant.

Depression is a common mental illness leading to upset or anxiety, with a high incidence rate in the world. Depression can lead to suicidal thoughts and behavior. The present study aimed to evaluate the effect of the direct oral anticoagulant rivaroxaban (RVX), in the model of depression induced by chronic unpredicted mild stress (CUMS) in rats. Fifty-six male Wister rats were randomly divided into seven experimental groups (8 rats/group); Group 1: Control group given vehicle per oral (p.o.), Group 2: RVXL-control group (received rivaroxaban 20 mg/kg/day, p.o..), Group 3: RVXH-control group (received rivaroxaban 30 mg/kg/day, p.o.), Group 4: chronic unpredictable mild stress (CUMS) group, Group 5: FLX-treated CUMS group (received fluoxetine 10 mg/kg/day, p.o..), Group 6: RVXL-treated CUMS group (received rivaroxaban 20 mg/kg/day, p.o.), and Group 7: RVXH-treated CUMS group (received rivaroxaban 30 mg/kg/day, p.o.). The rats received the drugs from the first day of the experiment and continued till 4 weeks—the duration of the study. The following were measured: monoamine neurotransmitters, malondialdehyde (MDA), total nitrite/nitrate (NOx), reduced glutathione (GSH), superoxide dismutase (SOD), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor‐kappa B (NF‐κB), tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor-A (VEGF-A). A forced swimming test (FST) was done. Furthermore, histological changes and glial fibrillary acidic protein (GFAP) immunoexpression were evaluated. CUMS showed a significant decrease in hypothalamic neurotransmitters, hippocampal GSH, SOD, BNDF, and VEGF-A with a significant increase in hippocampal MDA, NOx, NF-kβ, Myd88, TLR4, TNF-α, and GFAP immunoexpression. RVX showed significant improvement in all parameters (p-value < 0.0001). In conclusion, RVX in a dose-dependent manner possesses potent ameliorative effects against depression by reducing the oxidative stress and inflammatory process, through the regulation of the TLR4/Myd88/NF-kβ signaling pathway.

Myocardial infarction (MI) is a critical condition that can happen with high doses or rapid termination of beta blockers therapy. The study aimed to evaluate the potential anti-toxic value of DAP against isoproterenol (ISO) - induced MI. Twenty-eight male Wistar rats were used for the study. The rodents were assigned to four groups (n = 7) and the treatments were given for 12 days as follows; Group 1 (control): were administrated normal saline, Group 2 (DAP control): were administrated DAP (10 mg/kg/day IP), Group 3 (ISO group): were administrated ISO (100 mg/kg, IP on the 11th and 12th days of the experiment), and Group 4 (DAP + ISO): co-treated with DAP plus ISO. The measured parameters were cardiac malondialdehyde (MDA), reduced glutathione (GSH), total nitrite/nitrate (NOx), catalase (CAT), serum cardiac biomarkers; CK-MB, ALT, LDH, and ALK-PH. Also, interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), toll-like receptor 4 (TLR4), caspase-3 activity, and hepatic BAX and Bcl-2 were also assessed. Also, histological examination and vimentin immuno-expressions were studied. ISO group exhibited MI as evidenced by the elevation in serum cardiac biomarkers, MDA, NOx, IL-1β, TNF-α, and caspase-3 together with the reduction in GSH, Nrf2, HO-1 levels, and a faint vimentin immuno-reaction. Histological alterations revealing distorted cardiomyocytes; vacuolation, edema, pyknosis, and fragmentation were also noticed. DAP significantly ameliorated all the examined toxicity indicators. DAP revealed efficient ameliorative actions against ISO-caused MI by marked reduction in myocardial infarct size and suppressed oxidative stress, inflammation, and apoptosis via the up-regulation of the Nrf2/HO-1; TLR4/TNF-α signaling pathways.

Purpose Liver ischemia-reperfusion (I/R) injury is an inescapable problem. Diacerein, a chondro-protective drug, has antioxidant and anti-inflammatory effects. Its effect on liver I/R injury has not yet been fully clarified. Therefore, the current study aimed to detect its hepatic protective effect with the explanation of possible underlying mechanisms. Methods Adult male albino rats were assigned to 4 groups: sham group, diacerein pretreated sham group, I/R non-treated group, and I/R diacerein pretreated group. Serum liver enzymes, hepatic tissue oxidative stress parameters, inflammatory biomarkers mainly Toll-like receptors-4 (TLR4), and liver fatty acid binding protein (L-FABP) levels were determined. Histopathological examination of liver tissues and immunohistochemical studies of heat shock protein 70, nuclear factor-kappa B, and Cluster of Differentiation 68 were also done. Results Diacerein pretreatment has the ability to restore the hepatic I/R damaging effect, proved by the reduction of serum liver enzymes, the decrease of the oxidative stress and hepatic inflammation via down-regulation of TLR4/ NFκ-B signaling pathway together with the restoration of L-FABP level and improvement of the histopathological and immunohistochemical study findings in the hepatic tissue. Conclusion These results suggested the hepatoprotective effect of diacerein relies on its antioxidant and anti-inflammatory effects reducing TLR4/ NFκ-B signaling pathway.

Objectives Acute pancreatitis (AP) is a common severe critical illness with a high mortality rate. We aimed to study the effect of vinpocetine (Vinpo) in the treatment of AP because of its anti-inflammatory, antioxidant, and antiapoptotic effects. Materials and methods Thirty two adult male albino Wistar rats were randomized to four groups: control group, Vinpo group (20 mg/kg.P.O.), l -arginine group (two intraperitoneal injections of l -arginine 2.5 g/kg, 1 h apart), and Vinpo + L-arginine group. Vinpo administration was once daily for 7 consecutive days and started 1 h later after l -arginine administration. We measured serum enzyme biomarkers (lipase and amylase), levels of pancreatic malondialdehyde (MDA), total antioxidant capacity (TAC), reduced glutathione (GSH), total sulfhydryl (T-SH), total nitrite/nitrate (NOx), Interluken-6 (IL-6), tumor necrosis factor-alpha (TNF-α), Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Sirtuin type 1 (Sirt1), and caspase-3 activity. Furthermore; histological changes, anti-insulin, and inducible nitric oxide synthase (iNOS) immuno-expressions were examined. Results l -arginine group displayed AP as manifested by a significant increase in serum lipase and amylase, MDA, NOx, IL-6, TNF-α, caspase-3 with iNOS immuno-expression. Histological changes indicating marked pancreatic injury were observed together with a significant decrease in TAC, GSH, T-SH, Nrf2, Sirt1 levels, and anti-insulin immuno-expression. Vinpo showed a significant amelioration in all parameters. Conclusion Vinpo possesses potent ameliorative effects against AP by decreasing oxidative stress, inflammatory process, and apoptosis through regulation of the Sirt1/Nrf2/TNF-α pathway.

This study aimed to investigate the potential protective effects of vitamin E against gabapentin-induced chronic liver and kidney injury associated with the inhibition of biomarkers of apoptosis and tissue injury.Four groups of adult male rats were included; control, gabapentin (100 mg/kg/day), Vitamin E (80 mg/kg/day), and a combination of gabapentin and Vitamin E for 90 days. Serum levels of AST, ALT, LDH, ALP, urea, and creatinine were measured in addition to malondialdehyde (MDA), and reduced glutathione (GSH) tissue levels. P53 gene expression, histological, and immunohistochemical examinations were performed in liver and kidney tissue samples.Gabapentin increased AST, ALT, LDH, ALP, urea, creatinine, MDA, and p53 gene expression and it reduced GSH. Moreover, gabapentin administration caused structural changes in the hepatic and renal architecture with a weak Periodic acid-Schiff (PAS) reaction that reflects glycogen deposition in the liver and kidney and a positive immunoreaction for BCL2-associated X protein (BAX) that reflects activated apoptosis. Vitamin E significantly (p0.05) reversed the biochemical alterations associated with chronic gabapentin administration and improved the histopathological picture of hepatic and renal tissue with a partial inhibition of BAX.Chronic administration of gabapentin causes hepatic and renal impairments, which is ameliorated by Vitamin E; possibly due to the inhibition of biomarkers of apoptosis and tissue injury.

Pregabalin (PGB) drug abuse is common among the youth. It substituted tramadol before its recent schedule as a controlled drug since April 2019. PGB is an antiepileptic drug acting on the central nervous system. It blocks calcium channels regulating the action of neurotransmitters and causing prolonged depolarization. The present study aimed to investigate the toxic effect of long term pregabalin abuse on the reproductive function and body weight in both male and female albino rats and to evaluate the ameliorative effect of wheat germ oil (WGO). Forty-eight rats were randomly divided into eight groups. The first four groups were males and they were treated as follows: control group (1.5 mL saline), WGO group (1.5 mL L/kg), PGB group (300 mg/kg), and protective group (PGB + WGO). All doses were administrated once per day for 60 days by gastric gavage. The second four groups were females. They were divided and treated the same as the male groups. Pregabalin caused significant weight loss, decreased serum triglyceride level, and increased leptin gene expression in all rats. PGB affected male rats reproduction by decreasing total testosterone serum level and inhibiting spermatogenesis. Reproductive toxicity in females was caused by decreasing pituitary steroids, increasing gonadal hormones, and increasing the number of atretic ovarian follicles. Mechanism of toxicity may be attributed to the PGB oxidative stress effect that induced apoptosis and caused diffuse gonadal atrophy. WGO showed a protective effect on PGB induced toxicity as all measured parameters were relatively improved.

Drug-induced cardiotoxicity is a serious adverse effect that occurs during the administration of chemotherapeutic agents such as cyclophosphamide (CYC). Therefore, there is a critical need to find cardioprotective agents to keep the heart healthy. The current study aimed to investigate the protective effect of simvastatin (SIM) against CYC-induced heart damage and evaluate different mechanisms involved in mediating this effect, including the inflammasome/caspase1/interleukin1β (IL1β) pathway and endothelial nitric oxide synthase (eNOS). 36 rats were randomly assigned to one of four groups: a control group that received only vehicles, a CYC group that received CYC (150 mg/kg/day) i.p. on the fourth and fifth days, a CYC+SIM group that received SIM (10 mg/kg/day) orally for 5 days and CYC (150 mg/kg/day) i.p. on the fourth and fifth days, and a CYC+SIM+ Nitro- ω-L-arginine (L-NNA) group that received L-NNA (25 mg/kg/day, SIM (10 mg/kg/day) orally for 5 days and CYC (150 mg/kg/day) i.p. on the 4th and 5th days. The CYC group revealed an obvious elevation in cardiac enzymes and heart weights with toxic histopathological changes. Moreover, there was an increase in malondialdehyde (MDA), tumor necrosis factor-alpha (TNFα) levels, and up-regulation of the NLRP3inflammasome/caspase1/IL1β pathway. In addition, total antioxidant capacity (TAC), eNOS, reduced glutathione (GSH), and superoxide dismutase (SOD) significantly decreased. CYC-induced cardiotoxicity was most properly reversed by SIM through its anti-oxidant, anti-inflammatory, and anti-apoptotic actions with the stimulation of eNOS. The co-administration of L-NNA diminished the protective effect of SIM, indicating the essential role of eNOS in mediating this effect. Therefore, SIM ameliorated CYC-induced cardiotoxicity.

Methotrexate (MXT) is a chemotherapeutic drug that has been used in a wide range of clinical practices. Unfortunately, the administration of MXT during pregnancy may induce abortion, fetal deformities, and intrauterine growth retardation. Vitamin E is an antioxidant agent that can ameliorate free radical damage. The current work aimed to shed more light on the possible protective effect of vitamin E against MXT induced placental toxicity and to determine the possible mechanisms; biochemically, histologically, and immunohistochemically. Four groups were used: control pregnant, Vitamin E (VIT E) pregnant, Methotrexate (MXT) pregnant, and Vitamin E Methotrexate (VIT E-MXT) pregnant. The placental tissues were processed for light, immunohistochemical, and electron microscopic study. Other samples were obtained for biochemical study; the placental oxidant/antioxidant status was evaluated. The results showed that MXT caused various placental morphological changes in the form of distorted chorionic projection with an accumulation of hemosiderin granules in the trophoblastic cells. Maternal blood vessels showed a homogenous acidophilic material Edema of the extra-embryonic fetal membranes was noticed. A significant decreased in placental weight as well as increase in the oxidative and inflammatory markers were detected. Increased COX2 and decreased eNOS expressions were observed in the MXT group if compared to the control group. VIT E significantly restored the normal histological and immunohistochemical appearance, placental weight, and oxidant/antioxidant balance. It could be concluded the biochemical, morphological, and morphometric findings suggested that vitamin E coadministration is promising in attenuating the placental toxic effect of methotrexate. In this study, VIT E decreased the inflammatory and oxidative stress effect of methotrexate on the placental tissue by enhancing the level of eNOS.

The majority of liver-related illnesses are caused by occupational and domestic exposure to toxic chemicals like formaldehyde (FA), which is widely common in Africa and the world at large. Hence, measures should be taken to protect humans from its hazardous effects. This study, therefore, examines the protective potential of Ganoderma lucidum (100 mg/kg body weight) on formaldehyde-induced (40%) liver oxido-inflammation in male rats. Male Wistar rats, 150&ndash, 200 g, were allotted into four groups of 10 animals as follows: Group 1 was orally treated with 1 mg/mL distilled water, Group 2 was exposed to a 40% formaldehyde vapor environment for 30 min per day, Group 3 was orally treated with 100 mg/kg ethanol extract of Ganoderma lucidum, and Group 4 was co-administered formaldehyde and 100 mg/kg ethanol extract of Ganoderma lucidum. Rats were then sacrificed 24 h after administering the last dose of treatment, and the livers were excised. Ganoderma lucidum significantly reversed the formaldehyde-mediated reduction in body and organ weight. Ganoderma lucidum administration significantly prevented oxido-inflammation by reducing the levels of hydrogen peroxide and malondialdehyde and increasing the activity of antioxidant enzymes and glutathione contents, as well as the normal level of nitrite and myeloperoxidase production in FA-treated rats. Additionally, Ganoderma lucidum reversed a large decline in proinflammatory markers in formaldehyde. Furthermore, Ganoderma lucidum restores formaldehyde-induced histological alterations in the liver. Collectively, our results provide valuable information on the protective potential of Ganoderma lucidum in protecting formaldehyde-induced liver oxido-inflammation in male rats.

Torture is the most serious violation of a person's fundamental right to personal integrity and a pathological form of human interaction. In this study, the prevalence of torture in Cairo during the years 2009 & 2010 is 10.97% of the total number of cases examined at the medico legal authority of Egypt in Zenhom (11.29% in 2010 & 10.36% in 2009). The number of cases under this study is 367 (175 cases in 2009, 192 cases in 2010). Torture is more prevalent in the year 2010 than in the year 2009. The largest prevalence of torture was found in the area of south Cairo (120 cases; 32.7%) while the least was found in the area of west Cairo (50 cases; 13.6%). The victims included 336 males (91.6%) and 31 females (8.4%) with male to female ratio 10.8: 1. The most commonly affected age group in the studied victims was the age group of the third decade (171 cases; 46.6%) while the least was the age group above the sixth decade (6 cases; 1.6%). The most commonly affected site of injury was head & neck (243 cases; 66.2%) while the least was abdomen (17 cases; 4.6%). The most common type of injury was bruises (258 cases; 70.3%) while the least was electrocution (5 cases; 1.4%). Regarding the causal instrument, the most commonly used instrument was blunt object (333 cases; 90.7%) while the least was electric current (5 cases; 10%). Hitting with a stick leaving the characteristic shape of elongated abrasion & bruises was found in 35 cases (9.5%) and characteristic lesion of handcuff, which is blunt trauma wounds around wrists or ankles, was found in 68 cases (18.5%). There was one case of hair torture (0.3%) & 5 cases of sexual torture (1.5%). Permanent infirmity left in victims was positive in 24 cases (6.5%) and negative in 343 cases (93.5%) while deformity left in victims was positive in 10 cases (3%) and negative in 357 cases (97%). All permanent infirmity cases were male. Of the 24 cases of permanent infirmity, 83.3% were subjected to blunt trauma and 79.2% were injured in the upper limbs & this is statistically significant.