Simvastatin attenuates aluminium chloride-induced neurobehavioral impairments through activation of TGF-ß1/ SMAD2 and GSK3ß/ß-catenin signalling pathways.

Alzheimer's disease (AD) is a neurodegenerative disease characterised by the presence of ß-amyloid plaques and acetylcholine depletion leading to neurobehavioral defects. AD was contributed also with downregulation of TGF-ß1/SMAD2 and GSK3ß/ß-catenin pathways. Simvastatin (SMV) improved memory function experimentally and clinically. Hence, this study aimed to investigate the mechanistic role of SMV against aluminium chloride (AlCl3) induced neurobehavioral impairments. AD was induced by AlCl3 (50 mg/kg) for 6 weeks. Mice received Simvastatin (10 or 20 mg/kg) or Donepezil (3 mg/kg) for 6 weeks after that the histopathological, immunohistochemical and biochemical test were examined. Treatment with SMV improved the memory deterioration induced by AlCl3 with significant recovery of the histopathological changes. This was concomitant with the decrease of AChE and Aß (1-42). SMV provides its neuroprotective effect through upregulating the protein expression of ß-catenin, TGF-ß1 and downregulating the expression of GSK3ß, TLR4 and p-SMAD2.

Dermatological Lesions of Cholesterol Embolisation Syndrome and Kaposi Sarcoma Mimic Primary Systemic Vasculitis: Case report study.

Primary systemic vasculitis can present with a wide spectrum of manifestations ranging from systemic non-specific features such as fever, malaise, arthralgia and myalgia to specific organ damage. We describe two cases of cholesterol embolisation syndrome and Kaposi sarcoma mimicking primary systemic vasculitis, both of which were characterised by features such as livedo reticularis, blue toe syndrome, a brown purpuric skin rash and positive perinuclear anti-neutrophil cytoplasmic antibodies associated with Kaposi sarcoma. Establishing the right diagnosis was challenging and thus this report aimed to highlight the possible ways to distinguish them from primary systemic vasculitis.

Arctigenin improves neuropathy via ameliorating apoptosis and modulating autophagy in streptozotocin-induced diabetic mice.

BACKGROUND: Oxidative stress mediates the pathophysiology of diabetic neuropathy (DN) with activation of apoptotic pathway and reduction of autophagy. Arctigenin (ARC) is a natural lignan isolated from some plants of the Asteraceae family that shows antioxidant property. The present study aimed to explore the mechanistic neuroprotective effect of ARC on animal model for DN. METHODS: DN was induced using streptozotocin (STZ) at a dose of 45 mg/kg, i.p, for five consecutive days and ARC was administered orally (25 or 50 mg) for 3 weeks. The mechanical sensitivity and thermal latency were determined using von Frey and hotplate, respectively. Beclin, p62, and LC3 were detected as markers for autophagy by western blot. Levels of reduced glutathione, lipid peroxides, and activities of catalase and superoxide dismutase were detected as readout for oxidative stress. Apoptotic parameters and histopathological changes were revealed in all experimental groups. RESULTS: The present study showed deterioration of the function and structure of neurons as a result of hyperglycemia. Oxidative stress and impaired autophagy were observed in diabetic neurons as well as the activation of apoptotic pathway. ARC improved the behavioral and histopathological changes of diabetic mice. ARC combated oxidative stress through diminishing lipid peroxidation and improving the activity of antioxidant enzymes. This was concomitant by reducing the biomarkers of apoptosis. ARC augmented the expression of Beclin and LC3 while it lessened the expression of p62 indicating the activation of autophagy. These findings suggest that ARC can ameliorate DN by combating apoptosis and oxidative stress and improving autophagy.

Possible Protective Potency of Argun Nut (Medemia argun - An Ancient Egyptian Palm) against Hepatocellular Carcinoma in Rats.

IntroductionHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Medemia argun (MA) fruits have been found to possess proanthocyanidins (PACs), having antioxidant activity. Methods: Intraperitoneal (IP) diethyl nitrosamine (DENA; 200 mg/kg, once) and carbon tetra chloride (CCl4, 3 ml/kg/week, subcutaneously, for 6 weeks) induced HCC in rats. Animals groups: Group I; received vehicle (control). Group II; received MA seed extract, 100 mg/kg (twice/week) for 12 weeks, IP. Group III; received carcinogenic agents only. Group IV; received MA for two weeks before administration of DENA/CCl4 till the end of the experiment. The total period of the experiment was three months. Results: DENA and CCl4 induced HCC, elevated serum alpha-fetoprotein (AFP), liver size, weight, tissue lymphocytic infiltration, nuclear/cytoplasmic ratio, collagen fiber and polysaccharide deposition, cellular proliferation, excessive pro-apoptotic caspase-3 accumulation, disrupted apoptosis. MA prior to DENA/CCl4, significantly protected liver against cancer progression, indicated by serum enzymes, antioxidant markers(glutathione, nitric oxide, and depressed malondialdehyde contents) in the MA-pretreated group, compared to the HCC one, without apparent useful action on superoxide dismutase activity, enhanced apoptosis in liver, through increased casapase-3 expression. The HCC group showed decreased antioxidant defense and BAX/Bcl-2 ratio. Conclusions: This study assumes that MA has a chemo-preventive effect against hepatocarcinogenesis.

Dapagliflozin attenuates diabetic cardiomyopathy through erythropoietin up-regulation of AKT/JAK/MAPK pathways in streptozotocin-induced diabetic rats.

PURPOSE: This study was designed to investigate the mechanism of Dapagliflozin (Dapa) cardioprotection against diabetic cardiomyopathy (DCM). Structural and functional changes in the heart as well as decrease of erythropoietin (EPO) levels were reported in DCM. EPO simultaneously activates three pathways: the Janus-activated kinase-signal transducer and activator of transcription (JAK2/STAT5), phosphatidylinositol-3-kinase-Akt (PI3K/Akt), and extracellular signal-related kinase (ERK/MAPK) cascades, that result in proliferation and differentiation of cardiac cells. METHODS AND RESULTS: DCM was induced by a high fat diet for 10 weeks followed by administration of streptozotocin. After confirmation of diabetes, rats were divided randomly to 5 groups: Group 1; normal control group, Group 2; untreated diabetic group and Groups (3-5); diabetic groups received Dapa daily (0.75 mg, 1.5 or 3 mg/Kg, p.o) respectively for a month. At the end of the experiment, full anaesthesia was induced in all rats using ether inhalation and ECG was recorded. Blood samples were collected then rats were sacrificed and their heart were dissected out and processed for biochemical and histopathological studies. Untreated diabetic rats showed abnormal ECG pattern, elevation of serum cardiac enzymes, decrease EPO levels, downregulation of P-Akt, P-JAK2 and pMAPK pathways, abnormal histological structure of the heart and increase immunostaining intensity of P53 and TNF α in the cardiomyocytes. Dapa in a dose dependent manner attenuated the alterations in the previously mentioned parameters. CONCLUSION: The cardioprotective effect of Dapa could be mediated by increasing EPO levels and activation of P-Akt, P-JAK2 and pMAPK signalling cascades which in turn decrease apoptosis.

Violence and depression among pregnant women in Egypt.

BACKGROUND: Depression is a serious mental health disorder that might affect women in the childbearing period. Incidences increase during pregnancy as well as after delivery. Its association with intimate partner violence (defined as physical, sexual, or psychological harm by a current or former partner) has been reported in many countries. Data about this sensitive issue are lacking in Egypt. The aim of the study was to determine the relation between intimate partner violence and depression during pregnancy. METHODS: This was a case control study conducted at the outpatient clinics in Suez Canal University hospital, from January 2019 to March 2020. The study included two groups, the study group included women exposed to violence during the current pregnancy and a control one included women with no history of violence. Both groups were recruited according to the predetermined inclusion criteria (women aged 18-45 years, continuous marital relationship, no history of depression in current or previous pregnancies, and singleton pregnancy). Women were asked to complete the Arabic validated NorVold Domestic Abuse Questionnaire (measuring four types of abuse: emotional, physical, sexual, and violence in the health care system, the last one being excluded). Depression was evaluated using the Arabic validated form of the Edinburgh Postnatal Depression Scale (comprises 10 questions that represent patients' feelings in the last 7 days). The main outcome measure was to assess the association between intimate partner violence and depression. RESULTS: We recruited 158 women in each group. Both groups were matched in their demographic characters. Although emotional violence was reported prominently among women exposed to IPV 87.9% (139/158), it was not significantly reported in depressed women (P value 0.084). Physical and sexual violence were significantly reported among depressed women (P value 0.022 and 0.001, respectively). There was a significant difference between women exposed to violence and those who were not exposed to violence in the total depression scores (13.63 ± 5.47 and 10.65 ± 5.44, respectively with a p value < 0.001). Emotional (p value < 0.001) and sexual violence (mild and severe with p value of 0.026 and 0.002 respectively) had significant roles as risk factors for depression during pregnancy in single regression and after control of other confounders. CONCLUSION: There was a strong association between intimate partner violence and depression during pregnancy.

Prediction of intraperitoneal adhesions using striae gravidarum and scar characteristics in women undergoing repeated cesarean sections.

BACKGROUND: The current fact of increasing rates of cesarean deliveries is a catastrophe. Recurrent cesareans result in intraperitoneal adhesions that would lead to maternal morbidity during delivery. Great efforts are directed towards the prediction of intraperitoneal adhesions to provide the best care for laboring women. The aim of the current study was to evaluate the role of abdominal striae and cesarean scar characters in the prediction of intraperitoneal adhesions. METHODS: This was a case- control study conducted in the emergency ward of the obstetrics and gynecology department of a tertiary hospital from June to December 2019. The study was carried on patients admitted to the ward fulfilling particular inclusion and exclusion criteria. The study included two groups, group one was assessed for the presence of striae, and the degree of intraperitoneal adhesions was evaluated during the current cesarean section. Group two included patients without evidence of abdominal striae. They were evaluated for the severity of adhesions also after evaluation of the previous scar. Evaluation of the striae was done using Davey's scoring system. The scar was assessed using the Vancouver Scar Scale. The modified Nair's scoring system was used to evaluate intraperitoneal adhesions. RESULTS: The study group included 203 women, while the control group included 205 women. There were significant differences in the demographic characters of the recruited patients (p-value 0.001 for almost all variables). The mean Davey score in those with mild, moderate, and severe striae was 1.82 ± 0.39, 3.57 ± 0.5, and 6.73 ± 0.94, respectively (p-value < 0.001). Higher scores for the parameters of the Vancouver scale were present in patients with severe striae (1.69 ± 1.01, 1.73 ± 0.57, 2.67 ± 1.23, and 1.35 ± 1.06 for scar vascularity, pigmentation, pliability, and height respectively with a p-value of < 0.001 each). Thick intraperitoneal adhesions were noted significantly in women with severe striae [21 (43.75%), p-value < 0.001)]. The Davey's and Vancouver scores showed highly significant predictive performance in the prediction of intraperitoneal adhesions (p-value < 0.001). CONCLUSION: Abdominal striae and cesarean scar were significant predictors for intraperitoneal adhesions.

Violence and sexual dysfunction among infertile Egyptian women.

OBJECTIVE: To evaluate domestic violence and sexual dysfunction in infertile women. MATERIALS AND METHODS: We recruited women complaining of infertility (primary or secondary infertility). A control group of fertile women attending the outpatient clinic for any concern was recruited. Domestic violence was evaluated using the Arabic validated NorVold Domestic Abuse Questionnaire (NORAQ). Female sexual function was evaluated using the Arabic validated female sexual function index. RESULTS: There was no significant difference between both groups in rates of exposure to violence (p-value 0.830). Primary infertility was a significant contributing factor in infertile women's exposure to violence (p-value 0.001). All the studied population had female sexual dysfunction, with more dysfunction was reported by the infertile women (total score 18.87 ± 5.92, 19.51 ± 5.42, p-value 0.072). They differed significantly in arousal (2.83 ± 1.33, 3.13 ± 1.29, p-value 0.001) and satisfaction (3.98 ± 1.27, 4.28 ± 1.28, p-value 0.003) which were impaired in infertile women. CONCLUSIONS: The recruited infertile women were exposed to violence. Emotional abuse was the most common reported type of violence. Sexual dysfunction was reported in the entire studied population with no significant difference relating to fertility.

Jaceidin Flavonoid Isolated from Chiliadenus montanus Attenuates Tumor Progression in Mice via VEGF Inhibition: In Vivo and In Silico Studies.

Phytochemical study of Chiliadenus montanus aerial parts afforded six compounds; Intermedeol (1), 5α-hydroperoxy-ß-eudesmol (2), 5,7-dihydroxy-3,3',4'-trimethoxyflavone (3), 5,7,4'-trihydroxy-3,6,3'-trimethoxyflavone (jaceidin) (4), eudesm-11,13-ene-1ß,4ß,7α-triol (5) and 1ß,4ß,7ß,11-tetrahydroxyeudesmane (6). These compounds were identified based on their NMR spectral data. The isolated compounds were tested for their cytotoxicity against liver cancer cell line (HepG2) and breast cancer cell line (MCF-7). Jaceidin flavonoid (4) exhibited the highest cytotoxic effect in vitro. Therefore, both of jaceidin and C. montanus extract were evaluated for their in vivo anti-tumor activity against Ehrlich's ascites carcinoma (EAC). Compared to control group, jaceidin and C. montanus extract decreased the tumor weight, improved the histological picture of tumor cells, lowered the levels of VEGF and ameliorate the oxidative stress. Molecular docking and in silico studies suggested that jaceidin was a selective inhibitor of VEGF-mediated angiogenesis with excellent membrane permeability and oral bioavailability.

Evaluation of the severity of striae gravidarum in women with pelvic organ prolapse.

OBJECTIVE: To evaluate the severity of abdominal striae in women presenting with pelvic organ prolapse. STUDY DESIGN: A cross sectional study conducted in the outpatient clinics of obstetrics and gynecology department, Suez Canal University hospitals. We recruited patients over a six months period from January 2019 to June 2019 presenting with symptomatic pelvic organ prolapse (96) and abdominal striae. A control group with no evidence of striae and presenting with symptomatic organ prolapse were recruited also. The degree of prolapse was evaluated using the pelvic organ prolapse quantification system. The evaluation of striae was done using the Davey's scale. RESULTS: Mild, moderate and severe striae affected 20 (20.8 %), 34 (35.4 %), and 42 (43.8 %) women, respectively. Severe striae were noted in women with increased parity (5 ± 2.03). Apical prolapse was more prominent in women with severe striae [42 (100 %)]. Advanced grades of prolapse (grade 3 and 4) were noted in women with severe striae [25 (59.5 %) and 9 (21.5 %) respectively]. Using simple linear regression analysis, abdominal striae was considered a risk factor for the development of POP (P value <0.001); however, when combined with other risk factors in a multivariate model, it had no effect on the development of POP. CONCLUSION: Women with severe abdominal striae were found to have advanced degrees of POP with the apical compartment affected obviously.

Exenatide ameliorates experimental non-alcoholic fatty liver in rats via suppression of toll-like receptor 4/NFκB signaling: Comparison to metformin.

AIMS: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease. This study aimed to evaluate the role of exenatide compared with metformin in halting the progression of fatty liver stimulated by a high-fat diet (HiFD) in rats. MAIN METHODS: Thirty male Wistar rats were allocated into 6 groups, 5 rats per each group. Group I: maintained on normal diet (normal group) for fourteen weeks. The other five groups were kept on HiFD throughout the experiment, HiFD was administered beside pharmacological treatments/or vehicle. Group II: (NAFLD control group), group III: received metformin (60 mg/kg/day, P.O.), group IV-VI: received exenatide (10, 20, and 40 µg/kg/day, S.C.) respectively for 7 weeks. At the end of the therapeutic period, fasting blood glucose was determined, and body weight was registered. Rats were sacrificed, and blood samples were taken to measure serum insulin, lipids, and liver enzymes. The liver index and homeostasis model of insulin resistance (HOMA-IR) index were calculated. Further, livers were dissected for histopathological examination and Western blot analysis. KEY FINDINGS: NAFLD control group showed hyperglycemia, hyperinsulinemia, increased liver enzymes, hypertriglyceridemia, elevated hepatic lipid peroxides, and inflammatory mediators (interlukin 6, nuclear factor-κB, tumor necrosis factor-α and Toll-like receptor4) in addition to hepatic fatty degeneration. In a dose-dependent manner, exenatide significantly improved most of the above mentioned markers in comparsion with NAFLD at P≤0.05. SIGNIFICANCE: The current results suggest that exenatide is equivalent to metformin in controlling insulin resistance, body weight gain, improving liver function, suppressing inflammation, and attenuating NAFLD progression in male rats.

Antenatal cervical length measurement as a predictor of successful vaginal birth.

BACKGROUND: Antenatal cervical length measurement has paramount importance in the prediction of labor. It was compared to the Bishop Score and incorporated in the modified Bishop score due to its relevance and convenience. It is a more accurate tool that imposes no harm or distress to the patients. The study aimed to evaluate the role of antenatal cervical length measurement in the prediction of a successful vaginal birth and its relation to the duration of labor. METHODS: This was a prospective cohort study, conducted at the emergency ward of obstetrics and gynecology department. We recruited 162 women over 1 year from January 2018 to January 2019. Women eligible for the study had a transvaginal ultrasound for the examination of the cervical length before the onset of labor. The success of vaginal delivery was evaluated. RESULTS: The mean cervical length (mm) was 43.3 ± 8.0. The majority of the patients labored spontaneously [102 (63.0%)] while the remaining ones required induction of labor due to different causes. One hundred and eight patients (66.7%) had a successful vaginal delivery. The cervical length was significantly shorter among patients who delivered vaginally than those delivered by CS (P-value < 0.001). Multiple factors had a significant role in the prediction of the mode of delivery (cervical length, BMI, the onset of labor, parity). Maternal body mass index and labor induction were associated with a prolonged duration of the active phase of labor. CONCLUSION: Antenatal cervical length measurement predicted the mode of delivery as well as the gestational age at which delivery ensued. It can be used in patients' counseling regarding the mode of delivery.

Nano selenium ameliorates oxidative stress and inflammatory response associated with cypermethrin-induced neurotoxicity in rats.

Cypermethrin (CYP), a class II synthetic pyrethroid, is used to control household insects. CYP can cross the blood-brain barrier to exert neurotoxicity through changes in sodium ion channels. Selenium is an essential component of glutathione peroxidise enzyme; in addition, it shows a potential anti-inflammatory property. The present study aimed to investigate the neuroprotective role of Nano-Se on CYP-induced neurotoxicity. Twenty-four adult male Wister rats were randomly divided into three groups: a) control, b) CYP (1mg/kg) administered orally for 21 days, c) CYP (1mg/kg) administered orally for 21 days and Nano-Se (2.5 mg/kg) given once a day three times a week for three weeks). Locomotor activity was assessed using open field test then rats were sacrificed under anaesthesia, and their brains were dissected out and processed for biochemical and histopathological studies. Histological examination of CYP-treated rats demonstrated some degenerative changes; besides, CYP affected rat locomotor activity. CYP-treated rats showed increased levels of malondialdehyde (MDA), TNF-α and IL-1ß in addition to the reduction of glutathione (GSH) levels and gamma-Aminobutyric acid (GABA). Nano-Se restored normal behavioural function and significantly attenuated CYP-evoked degenerative changes. Nano-Se increased levels of GABA and glutathione; on the other hand, it significantly prevented the rise in the levels of MDA, TNF-α and IL-1ß. Therefore, Nano-Se demonstrated both anti-oxidant and anti-inflammatory potential. Nano-Se may be suggested to be a prospective candidate to ameliorate CYP-induced neurotoxicity.

Evaluation and ranking of different interventions for pain relief during outpatient hysteroscopy: A systematic review and network meta-analysis.

AIM: To identify the highest-ranked pharmacological and nonpharmacological interventions for pain relief during outpatient hysteroscopy. METHODS: We conducted an online bibliographic search in different databases from inception till July 2019. We included randomized controlled trials assessing effect of pharmacological and nonpharmacological interventions on pain relief during outpatient hysteroscopy. Our main outcomes were pain scores at different endpoints of the procedure. We applied this network meta-analysis based on the frequentist approach using statistical package 'netmeta' (version 1.0-1) in R. RESULTS: The review included 39 randomized controlled trials (Women n = 3964). Misoprostol plus intracervical block anesthesia (mean difference [MD] = -3.32, 95% confidence interval [CI] [-6.06, -0.59]), misoprostol (MD = -1.92, 95% CI [-3.04, -0.81]) and IV analgesia (MD = -2.01, 95% CI [-3.27, -0.25]) were effective in reducing pain during the procedure compared to placebo. Ranking probability showed that misoprostol plus intracervical block anesthesia was the highest ranked pharmacological treatment for pain relief during the procedure (P score = 0.92) followed by misoprostol alone (P score = 0.78), and IV analgesia (P score = 0.76). Regarding nonpharmacological treatments, transcutaneous electrical nerve stimulation (TENS) showed a significant pain reduction compared to placebo (MD = -1.80, 95% CI [-3.31, -0.29]). TENS ranked as the best nonpharmacological treatment (P score = 0.80) followed by CO2 distention (P score = 0.65) and bladder distention (P score = 0.60). CONCLUSION: Combination of misoprostol plus local anesthesia appears to be the most effective pharmacological approach for pain reduction during and after outpatient hysteroscopy. Nonpharmacological approaches as TENS and bladder distention showed considerable efficacy but should be further investigated.

Donepezil improves neuropathy through activation of AMPK signalling pathway in streptozotocin-induced diabetic mice.

Diabetic neuropathy (DN) is a common complication of diabetes mellitus and is associated with structural changes in the nerves. However, the molecular basis for DN is poorly understood. Adenosine monophosphate activated protein kinase (AMPK) has been shown to regulate the activity of some kinases including protein kinase B (AKT), mitogen-activated protein kinases (MAPK) and mammalian target of rapamycin complex 1 (mTORC1) that represent important signalling pathways modulating the function of peripheral nociceptive neuron. Donepezil can activate AMPK and exerts neuroprotective effects. In this study, streptozotocin (45 mg/kg for 5 Day, i.p.) was used to induce experimental DN. After confirmation of development of neuropathy, mice were randomly distributed into five groups: Group 1; negative control group received saline (0.9%NaCl), Group 2; diabetic mice received saline, Group (3-5); diabetic mice received daily donepezil (1, 2 or 4 mg/kg, p.o.) respectively for 20 days. Mice were then sacrificed under anesthesia then their sciatic nerve and spinal cord were dissected out and processed for biochemical and histopathological studies. Diabetic mice revealed severe histological abnormalities including degenerated neurons in the spinal cord and swollen myelin sheath with inflammatory edema observed in sciatic nerves. In addition, diabetic mice showed reduced expression of p-AMPK in sciatic nerves with consequent activation of AKT/MAPK/4EBP1. A significant upregulation of the N-Methyl-d-aspartate (NMDA) receptors in both cervical and lumbar regions of spinal cord of diabetic mice was also demonstrated. Donepezil, an AMPK activator, blocked the phosphorylation of AKT/MAPK/4EBP1, down regulate the expression of NMDA receptors and reversed hyperalgesia developed in diabetic mice. Therefore, Donepezil could be a potential pharmacological agent for management of DN.

Survey of nuclear progesterone receptor expression in the uterus of the cyclic and pregnant camel (Camelus dromedarius).

Progesterone receptors (PR) are necessary to mediate the biological effects of progesterone and are integral to the regulation of a number of different aspects of reproduction in mammals including ovulation of the oocyte, implantation of the conceptus and maintenance of pregnancy. This study investigated the expression and localization of progesterone receptors in the uterine wall of both pregnant and cyclic (nonpregnant) camels. Uterine tissue samples were collected from healthy animals and processed for routine histological and immunohistochemical staining techniques to reveal nuclear PR. Demonstration of PR was performed by indirect immunohistochemical techniques using monoclonal antibodies raised against human PR. Immunolocalization of PR was more intense in all four endometrial zones (I-IV) as well as the myometrium of non pregnant (cyclic) animals (animals with newly formed corpus luteum). In contrast, PR immunostaining in both the endometrium and the myometrium was greatly reduced in pregnancy, particularly in the latest stage examined (approximately 366 days of gestation). In conclusion, a better understanding of the expression of steroid hormones and their receptors, including progesterone and the PR is critical to improving the reproductive health and pregnancy in the domesticated dromedary camel.

Cytotoxic effect of chlorpyrifos is associated with activation of Nrf-2/HO-1 system and inflammatory response in tongue of male Wistar rats.

Repeated administration of chlorpyrifos (CPF), an organophosphate pesticide, can increase the risk of oral cytotoxicity. The current study was designed to assess the mechanism by which CPF mediates its cytotoxic effect on lingual mucosa of rats. Twenty-four male Wistar rats were used in the present study and divided into three groups: group I: healthy rats (negative control), group II: rats treated with CPF 1/40 LD50 (3.375 mg/kg, orally/daily) for 28 days, group III: rats treated with CPF 1/10 LD50 (13.5 mg/kg, orally/daily) for 28 days. At the end of the experiment, all rats were sacrificed by cervical dislocation under ketamine anesthesia. Tongue samples were dissected out at their base for detection of heme oxygenase-1 (HO-1) and nuclear erythroid 2-related factor 2 (Nrf-2) by western blotting and histopathological and electron microscopic studies. Immunostaining was used to determine cleaved caspase 3 and the nuclear factor kappa B (NF-κB) localization. Structural and ultrastructural examination of treated lingual mucosa with CPF demonstrated degenerative changes that involved both the dorsal and ventral surfaces of the tongue as well as the lingual glands. CPF-treated rats demonstrated a significant increase in the levels of pro-inflammatory cytokines such as interleukin-1ß (IL-1ß) and tumor necrosis factor (TNF-α) in addition to a significant dose-dependent activation of NF-κB and cleaved caspase 3. Furthermore, CPF activated HO-1 and Nrf-2 pathway in a dose-dependent manner. In conclusion, this data suggests that the CPF-induced cytotoxicity may be explained by NF-κB activated inflammatory cascade. In addition, CPF triggers an adaptive activation of Nrf-2/HO-1 pathway.

Allicin ameliorates doxorubicin-induced cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis.

PURPOSE: Doxorubicin (DOX) is a highly active antineoplastic agent; however, its clinical use is limited due to associated cardiotoxicity. This study was performed to evaluate the beneficial effects of allicin, a dietary garlic active constituent against DOX-induced cardiotoxicity. METHODS: Forty male Swiss albino mice were divided into five groups, which received normal saline, oral allicin (20 mg kg-1 once daily), intraperitoneal DOX (on the 7, 9 and 11th day of the experiment), or DOX plus once daily allicin at 10 or 20 mg kg-1. Sera were collected for evaluation of cardiac injury markers and proinflammatory cytokines. Additionally, heart tissue spacemen were harvested for determination of oxidative stress markers, as well as for histopathological examination and immunohistochemical analysis. RESULTS: DOX administration induced significant (p < 0.05) reductions in cardiac tissue level of reduced glutathione and activities of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase). Moreover, it induced significant (p < 0.05) elevations in cardiac tissue concentrations of nitric oxide and malondialdehyde as well as serum levels of cardiac injury biomarkers (lactate dehydrogenase, creatine kinase, and creatine kinase-MB) and proinflammatory cytokines (interleukin-1ß, and tumor necrosis factor-alpha). The histopathological examination showed necrotic and degenerative changes in the cardiac tissue, while immunohistochemical analysis revealed marked myocardial expression of activated caspase-3 and cyclooxygenase-2, following DOX adminstration. Allicin pretreatment significantly improved (p < 0.05) all examined parameters, and restored the cardiac architecture. CONCLUSION: The current study demonstrated that allicin effectively mitigates cardiac oxidative damage, apoptosis and inflammation, induced by acute DOX intoxication. Therefore, allicin could be a promising cytoprotective agent against DOX cardiotoxicity.

Aspirin and (or) omega-3 polyunsaturated fatty acids protect against corticohippocampal neurodegeneration and downregulate lipoxin A4 production and formyl peptide receptor-like 1 expression in pentylenetetrazole-kindled rats.

There is evidence for a relationship between inflammation and seizures because epilepsy can be caused by or result in inflammation. This study aimed to investigate the effect of aspirin and (or) omega-3 polyunsaturated fatty acids (PUFAs) on seizure activity and neurodegeneration in pentylenetetrazole (PTZ)-kindled rats focusing on their effect on corticohippocampal production of lipoxin A4 (LXA4) and expression of formyl peptide receptor-like 1 (FPRL1) receptors. Male rats were injected with PTZ (35 mg/kg, i.p.) 3 times per week for a total of 15 doses. Rats were treated daily with aspirin (20 mg/kg, i.p.), omega-3 PUFAs (85 mg/kg, p.o.), or a combination of them for 35 days. Both LXA4 level and expression of FPRL1 receptor in the cortices and hippocampi of rats' brains were greater in PTZ-kindled rats compared to a saline control group. Cotreatment with aspirin and (or) omega-3 PUFAs reduced convulsive behaviour; reduced levels of LXA4, interleukin-1ß, and nuclear factor-κB; and showed a lower percentage of corticohippocampal degenerative cells compared to PTZ-kindled rats. The combination of the 2 therapeutic agents did not provide significant improvement in comparison with the monotherapies. These findings suggest the use of aspirin or omega-3 PUFAs may delay the development of seizures and provide neuroprotection in a clinical setting.