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Nagla A El-Shitany,1 Amina M Bagher,2 Lenah Saeed Binmahfouz,2 Basma G Eid,2 Haifa Almukadi,2 Shaimaa M Badr-Eldin,3,4 Manal El-Hamamsy,5 Zuhair M Mohammedsaleh,6 Fayez M Saleh,7 Mohammed S Almuhayawi,8 Samar A Alghamdi,9 Rana A Arab,10 Soad S Ali,11,12 Steve Harakeh,12,13 Badrah S Alghamdi14,15 1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt; 2Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 5Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt; 6Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia; 7Department of Medical Microbiology, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia; 8Department of Medical Microbiology/Parasitology and Molecular Microbiology Laboratory, King Abdulaziz University Hospital, Jeddah, Saudi Arabia; 9Department of Oral Biology, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia; 10Medicine Program, Ibn Sina National College for Medical Studies, Jeddah, Saudi Arabia; 11Department of Histology, Faculty of Medicine, Assiut University, Assiut, Egypt; 12Yousef Abdullatif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine (FM), King Abdulaziz University, Jeddah, Saudi Arabia; 13King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; 14Department of Physiology, Neuroscience Unit, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 15Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi ArabiaCorrespondence: Nagla A El-Shitany, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt, Email nagla_fouad@yahoo.com; naglaa.fouad@pharm.tanta.edu.egBackground: Like other vaccines, Pfizer BioNTech’s COVID-19 vaccine efficacy against SARS-CoV-2 virus infections begins to decline within a few months after the 2nd dose. On August 12, 2021, the FDA allowed additional Pfizer BioNTch’s COVID-19 vaccine dose (3rd or booster dose) for individuals with weakened immunity. This study aimed to evaluate the short-term adverse reactions (ADRs) of the 2nd and the 3rd doses of the Pfizer BioNTech COVID-19 vaccine.Methods: Information for this study was collected by Google Form questionnaire (online survey). The results included responses from 442 people, the majority from Saudi Arabia.Results: The most common local ADRs following the 3rd dose were injection site pain, injection site hypersensitivity, and axillary lymph node swelling. The most common systemic ADRs were fatigue, muscle pain, bone pain, headache, and fever less than 38ºC. Less common systemic ADRs were shivering, fever more than 38ºC, nasal congestion and rhinorrhea, arrhythmia, cough, abdominal pain, chest tightness, nausea, diarrhea, vomiting, and tachypnea. Rare systemic ADRs were constipation, dizziness and vertigo, lack of concentration, sore throat, excessive hair loss, dysmenorrhea and heavy menstruation, and Bell’s palsy. Severe allergic reactions were reported by 2.6% of participants after the 2nd dose, compared with none after the 3rd dose. Nasal congestion and runny nose are more frequent after the 3rd dose. The ADRs of the 2nd and 3rd doses were significantly more prevalent in females. 12% of participants reported ADRs lasting more than one week after the 3rd dose compared to 5% after the 2nd dose. People ≤ 60 years were more affected by the vaccine ADRs.Conclusion: Most of the ADRs reported after the 3rd vaccine dose were consistent with the Pfizer vaccine information sheet and similar to the 2nd dose ADRs.Keywords: Pfizer-BioNTech COVID-19 vaccine, adverse drug reactions, booster dose, second dose, injection site pain, fatigue, online questionnaire

Nagla A El-Shitany,1,2 Steve Harakeh,3 Shaimaa M Badr-Eldin,4,5 Amina M Bagher,1 Basma Eid,1 Haifa Almukadi,1 Badrah S Alghamdi,6 Ahlam A Alahmadi,7 Nibal A Hassan,8 Nariman Sindi,9 Samar A Alghamdi,10 Hailah M Almohaimeed,11 Zuhair M Mohammedsaleh,12 Turki M Al-Shaikh,13 Mohammed S Almuhayawi,14 Soad S Ali,15 Manal El-Hamamsy16,17 1Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt; 3Special Infectious Agents Unit, King Fahd Medical Research Center, Yousef Abdullatif Jameel Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 5Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 6Department of Physiology, Neuroscience Unit, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 7Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; 8Department of Biology, Faculty of Science, Taif University, Taif, Saudi Arabia; 9Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia; 10Department of Oral Biology, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia; 11Department of Basic Science, Faculty of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; 12Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia; 13Department of Biology, College of Science and Arts at Khulis, University of Jeddah, Jeddah, Saudi Arabia; 14Department of Microbiology and Medical Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 15Department of Histology, Faculty of Medicine, Assiut University, Assiut, Egypt; 16Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 17Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, EgyptCorrespondence: Nagla A El-ShitanyDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Al-Sheekh Kamal Street, Alsulimaniah, Jeddah, Saudi ArabiaTel +966 545923440Email nagla_fouad@yahoo.comBackground: The Pfizer-BioNTech COVID-19 vaccine has recently received emergency approval from the US FDA. The mRNA technology was used to manufacture the Pfizer vaccine; however, as a pioneering technology that has never been used in the manufacture of vaccines, many people have concerns about the vaccine’s side effects. Thus, the current study aimed to track the short-term side effects of the vaccine.Methods: The information in this study was gathered by a Google Form-questionnaire (online survey). The results included the responses of 455 individuals, all of whom are Saudi Arabia inhabitants. Adverse effects of the vaccine were reported after the first and the second doses.Results: The most common symptoms were injection site pain, headaches, flu-like symptoms, fever, and tiredness. Less common side effects were a fast heartbeat, whole body aches, difficulty breathing, joint pain, chills, and drowsiness. Rare side effects include Bell’s palsy and lymph nodes swelling and tenderness. Flu-like symptoms were more common among those under 60 years of age, while injection site pain was more frequent among recipients who were 60 years and older. The study revealed a significant increase in the number of females who suffered from the vaccine side effects compared to males. Difficulty of breathing was more reported among recipients who had been previously infected with the coronavirus compared to those who had not been previously infected.Conclusion: Most of the side effects reported in this study were consistent with Pfizer’s fact sheet for recipients and caregivers. Further studies are required to determine the long-term side effects.Keywords: Pfizer-BioNTech COVID-19 vaccine, side effects, injection site pain, hypersensitivity, flu-like symptoms, online survey

Nagla A El-Shitany,1,2 Karema El-Desoky3 1Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt; 3Department of Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt Abstract: Hepatic ischemia/reperfusion (ISCH/REP) is a major clinical problem that is considered to be the most common cause of postoperative liver failure. Recently, mast cells have been proposed to play an important role in the pathophysiology of ISCH/REP in many organs. In contrast, the role played by mast cells during ISCH/REP-induced liver damage has remained an issue of debate. This study aimed to investigate the protective role of mast cells in order to search for an effective therapeutic agent that could protect against fatal ISCH/REP-induced liver damage. A model of warm ISCH/REP was induced in the liver of rats. Four groups of rats were used in this study: Group I: SHAM (normal saline, intravenously [iv]); Group II: ISCH/REP; Group III: sodium cromoglycate + ISCH/REP (CROM + ISCH/REP), and Group IV: ketotifen (KET) + ISCH/REP (KET + ISCH/REP). Liver damage was assessed both histopathologically and biochemically. Mast cell degranulation was assessed histochemically. Lipid peroxidation (malondialdehyde [MDA]) as well as the levels of glutathione (GSH), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α), the formation of nitric oxide (NO), and the expression of inducible NO synthase (iNOS) were determined. The results of this study revealed increased mast cell degranulation in the liver during the acute phase of ISCH/REP. Moreover, CROM, but not KET, decreased the activity of alanine aminotransferase, aspartate aminotransferase, and lactic dehydrogenase and maintained normal liver tissue histology. Both CROM and KET protected against mast cell degranulation in the liver. In addition, both CROM and KET decreased IL-6 and TNF-α. However, CROM, but not KET, decreased MDA formation and increased GSH. Furthermore, KET, but not CROM, increased both NO formation and iNOS expression. In conclusion, this study clearly demonstrated mast cell degranulation in warm ISCH/REP in the liver of rats. More importantly, CROM, but not KET, ameliorated the effect of ISCH/REP-induced injury in rat liver. CROM may protect the liver through mast cell stabilization, inhibition of TNF-α, IL-6, MDA, and iNOS and increased GSH. KET may maintain ISCH/REP-induced liver injury through the NO/iNOS pathway. Keywords: ischemia/reperfusion, mast cells, liver, sodium cromoglycate, ketotifen, nitric oxide, inducible nitric oxide synthase

Marine algal extracts exhibit a potent inhibitory effect against several enveloped and non-enveloped viruses. The infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has several adverse effects, including an increased mortality rate. The anti-COVID-19 agents are still limited; this issue requires exploring novel, effective anti-SARS-CoV-2 therapeutic approaches. This study investigated the antiviral activity of an aqueous extract of Ulva lactuca , which was collected from the Gulf of Suez, Egypt. The aqueous extract of Ulva lactuca was characterized by high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and Energy Dispersive X-ray (EDX) analyses. According to the HPLC analysis, the extract comprises several sugars, mostly rhamnose (32.88%). The FTIR spectra showed numerous bands related to the functional groups. EDX analysis confirmed the presence of different elements, such as oxygen (O), carbon (C), sulfur (S), magnesium (Mg), potassium (K), calcium (Ca), and sodium (Na), with different concentrations. The aqueous extract of U. lactuca (0.0312 mg/mL) exhibited potent anti-SARS-CoV-2 activity via virucidal activity, inhibition of viral replication, and interference with viral adsorption (% inhibitions of 64%, 33.3%, and 31.1%, respectively). Consequently, ulvan could be a promising compound for preclinical study in the drug development process to combat SARS-CoV-2.

High levels of inflammatory cytokines in serum have been reported in patients with severe SARS-CoV-2 infection. There is growing interest in recognizing the role of inflammatory biomarkers in saliva in diagnosing systemic diseases. This study assumed that estimating biomarkers in saliva samples from patients infected with SARS-CoV-2 would distinguish between mild and severe cases. Saliva was collected from 142 controls and 158 SARS-CoV-2 patients (mild 72 and severe 86) to measure interleukin-6 (IL-6), C-reactive protein (CRP), and C-X-C motif chemokine ligand-10 (CXCL-10). IL-6 and CXCL-10 were significantly increased in patients with mild and severe SARS-CoV-2 infections. CRP was significantly increased only in severe SARS-CoV-2 cases. All biomarkers were significantly higher in severe cases than in mild cases ( p < 0.001). Among patients with SARS-CoV-2 infection, men showed significantly higher CRP and CXCL-10 levels than females ( p < 0.01 and 0.05, respectively). In addition, elderly patients (40-80 years) had significantly higher IL-6, CRP, and CXCL-10 ( p < 0.001). Patients with diabetes and hypertension showed elevated IL-6, CRP, and CXCL-10 ( p < 0.001). There was a significant positive correlation between IL-6, CRP, CXCL-10, and between age, IL-6, CRP, and CXCL-10. Saliva may have a future value in measuring the inflammatory biomarkers associated with the severity of SARS-CoV2 infection and therapeutic monitoring., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Hanadi Abdullah Alwafi et al.)

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in females of childbearing age and research findings have revealed a potential association between PCOS and renal dysfunction. This study aimed to investigate renal dysfunction that might be associated with PCOS in rats and to evaluate the potential protective effect of chamomile against PCOS complicated by kidney damage. A rat model of PCOS was induced by injecting estradiol valerate (0.2 mg/rat × 2) into adult virgin female rats. Rats were treated with either ethyl alcohol extract of chamomile flower (75 mg/kg/day) or metformin (Met) (500 mg/kg/day). Induction of PCOS was associated with increased relative right kidney weight percentage and increased serum levels of urea, lipid peroxide product, and testosterone. PCOS was also associated with increased p53 expression in kidney glomeruli and medullary tubules with decreased Bcl2 expression in kidney glomeruli. Administration of chamomile extract significantly decreased levels of serum urea, testosterone, and lipid peroxide product, and p53 expression in kidney glomeruli and tubules. The extract significantly increased levels of antioxidant markers levels (reduced glutathione, catalase, and superoxide dismutase) and the expression of the anti-apoptotic gene Bcl2. Conversely, administration of Met did not improve serum levels of urea. Met also exerted no pronounced effect on p53 gene expression. The results of this study highlight the importance of monitoring kidney function in patients with PCOS and investigating the associated underlying mechanism. Chamomile extract was found to ameliorate kidney damage associated with PCOS through antioxidant, testosterone-lowering, and anti-apoptotic mechanisms., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Cisplatin (Cis) is an effective cancer therapy commonly employed in many therapeutic regimens. However, treatment regimens that contain either a high dose or cumulative doses of Cis could trigger liver damage. A unique study demonstrated that captopril (Cap) protects against Cis-induced liver toxicity, but only some liver function enzymes and some antioxidant enzymes were investigated in that study. Our study aims to elucidate the protective mechanism of Cap against Cis liver toxicity. Acute liver toxicity was induced in rats by injecting a single Cis dose (7.5 mg/kg) in three groups (n = 6). Two groups were pre-treated with low (50 mg/kg) and high (100 mg/kg) Cap doses for one week before Cis injection, and the third group was injected with Cis only. The high Cap dose significantly improved liver function markers (ALT, AST, and ALP) and hepatic tissue pathology. The low Cap dose significantly improved ALP and, to a lesser extent, hepatic tissue pathology. Both Cap doses significantly decreased liver contents of MDA, IL-1β, and cleaved caspase-3; and liver protein expression of TNF-α, Bax, and caspase-3. The high Cap dose significantly increased liver contents of GSH, GPx, CAT, and SOD, and the liver protein expression of Bcl2. Moreover, only the high Cap dose significantly decreased liver IL-6 content and cytochrome C protein expression. Cap did not inhibit the antitumor impact of Cis against HCT116 cancer cells. Therefore, Cap restricts Cis-induced liver toxicity by reducing inflammation and apoptosis and augmenting the antioxidant system., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background and Objectives: Studies have noted that some ABO blood types are more susceptible to COVID-19 virus infection. This study aimed to further confirm the relationship between different blood groups on the vulnerability, symptoms, cure period, and severity among COVID-19 recovered patients. Subjects and Methods: This cross-sectional study approached the participants from the Arab community via social media (mainly Facebook and WhatsApp). The data were collected through two Google Form questionnaires, one for COVID-19 recovered patients (COVID-19 group, n = 726), and the other for the healthy people (Control group, n = 707). Results: The subjects with blood group O were the least likely to be infected with the COVID-19 virus, while those with blood group A were not likely to be the most susceptible. There were significant differences among different ABO blood groups regarding the distribution of oxygen saturation percentage, myalgia, and recovery time after COVID-19 infection ( p < 0.01, 0.01, and 0.05, respectively). The blood group A showed the highest percentage of patients who experienced an oxygen saturation range of 90-100%, whereas the blood group O showed the highest percentage of patients who experienced an oxygen saturation range of 70-80%. The blood group A showed the lowest percentage of patients who required artificial respiration, whereas the blood group O showed the highest percentage of patients who required artificial respiration. The blood group B showed the lowest percentage of patients who experienced myalgia and exhibited the lowest percentage of patients who needed 3 weeks or more to recover. Conclusion: The people of blood group O may be the least likely to be infected with COVID-19, however, they may be the more in need of treatment in hospital and artificial respiration compared to the other blood groups.

Cellular inflammation has been recognized as the leading factor in numerous diseases, causing either cell death, organ-specific damage, or genesis of different cancers. Icariin, a flavonol glucoside, extracted from Herba Epimedii, offers various pharmacological activities, including reducing inflammation and an antioxidant effect. We aimed to evaluate the anti-inflammatory mechanisms of icariin focussing on both HO-1/Nrf2 and NF-kB pathways. Acute inflammation was induced in rats via carrageenan in this study. Icariin was injected in a dose of 50 mg/kg. Icariin significantly reduced paw swelling in carrageenan-injected animals. It also ameliorated carrageenan-induced paw histopathological alterations. Icariin significantly increased paw enzymatic and non-enzymatic antioxidants. It decreased paw lipid peroxidation. Icariin decreased paw levels of inflammatory cytokines and NF-kB. The immunohistochemical analysis showed that icariin significantly increased Nrf2 gene expression while decreasing NF-kB and COX-2 gene expression. RT-PCR analysis revealed that icariin injection significantly increased both Nrf2 and HO-1 expression of mRNA. The results of this study collectively show that icariin improved carrageenan-induced paw edema by modulating HO-1/Nrf2 and NF-ĸB signaling., (Copyright © 2019 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Gastric ulcers are a major problem worldwide with no effective treatment. The objective of this study was to evaluate the use of manuka honey in the treatment of acetic acid-induced chronic gastric ulcers in rats. Different groups of rats were treated with three different concentrations of honey. Stomachs were checked macroscopically for ulcerative lesions in the glandular mucosa and microscopically for histopathological alterations. Treatment with manuka honey significantly reduced the ulcer index and maintained the glycoprotein content. It also reduced the mucosal myeloperoxidase activity, lipid peroxidation (MDA), and the inflammatory cytokines (TNF- α , IL-1 β , and IL-6) as compared to untreated control group. In addition, honey-treated groups showed significant increase in enzymatic (GPx and SOD) and nonenzymatic (GSH) antioxidants besides levels of the anti-inflammatory cytokine IL-10. Flow cytometry studies showed that treatment of animals with manuka honey has normalized cell cycle distribution and significantly lowered apoptosis in gastric mucosa. In conclusion, the results indicated that manuka honey is effective in the treatment of chronic ulcer and preservation of mucosal glycoproteins. Its effects are due to its antioxidant and anti-inflammatory properties that resulted in a significant reduction of the gastric mucosal MDA, TNF- α , IL-1 β , and IL-6 and caused an elevation in IL-10 levels., Competing Interests: All authors have no competing interests whatsoever.

The Food and Drug Administration recently warned of the fatal cardiovascular risks of azithromycin in humans. In addition, a recently published study documented azithromycin-induced cardiotoxicity in rats. This study aimed to justify the exact cardiovascular events accompanying azithromycin administration in rats, focusing on electrocardiographic, biochemical, and histopathological changes. In addition, the underlying mechanisms were studied regarding reactive oxygen species production, cytokine release, and apoptotic cell-death. Finally, the supposed protective effects of both carvedilol and vitamin C were assessed. Four groups of rats were used: (1) control, (2) azithromycin, (3) azithromycin + carvedilol, and (4) azithromycin + vitamin C. Azithromycin resulted in marked atrophy of cardiac muscle fibers and electrocardiographic segment alteration. It increased the heart rate, lactate dehydrogenase, creatine phosphokinase, malondialdehyde, nitric oxide, interleukin-1 beta (IL1-β), tumor necrosis factor alpha (TNF-α), nuclear factor kappa beta (NF-κB), and caspase-3. It decreased reduced glutathione, glutathione peroxidase, and superoxide dismutase. Carvedilol and vitamin C prevented most of the azithromycin-induced electrocardiographic and histopathological changes. Carvedilol and vitamin C decreased lactate dehydrogenase, malondialdehyde, IL1-β, TNF-α, NF-κB, and caspase-3. Both agents increased glutathione peroxidase. This study shows that both carvedilol and vitamin C protect against azithromycin-induced cardiotoxicity through antioxidant, immunomodulatory, and antiapoptotic mechanisms.

Gastric ulcers are among the most common diseases affecting humans. This study aimed at investigating the gastroprotective effects of manuka honey against ethanol-induced gastric ulcers in rats. The mechanism by which honey exerts its antiulcer potential was elucidated. Four groups of rats were used: control, ethanol (ulcer), omeprazole, and manuka honey. Stomachs were examined macroscopically for hemorrhagic lesions in the glandular mucosa, histopathological changes, and glycoprotein detection. The effects of oxidative stress were investigated using the following indicators: gastric mucosal nitric oxide (NO), reduced glutathione (GSH), lipid peroxide (MDA, measured as malondialdehyde) glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase. Plasma tumour necrosis factor-α, interleukin-1β, and IL-6 were also measured. Manuka honey significantly decreased the ulcer index, completely protected the mucosa from lesions, and preserved gastric mucosal glycoprotein. It significantly increased gastric mucosal levels of NO, GSH, GPx, and SOD. Manuka honey also decreased gastric mucosal MDA and plasma TNF-α, IL-1β, and IL-6 concentrations. In conclusion, manuka honey likely exerted its antiulcer, effect by keeping enzymatic (GPx and SOD) and nonenzymatic (GSH and NO) antioxidants as well as inflammatory cytokines (TNF-α, IL-1β, and IL-6) in a reduced form, inhibited lipid peroxidation (MDA), and preserved mucous glycoproteins levels.

Marine sponges are found to be a rich source of bioactive compounds which show a wide range of biological activities including antiviral, antibacterial, and anti-inflammatory activities. This study aimed to investigate the possible anti-inflammatory, antioxidant and immunomodulator effects of the methanolic extract of the Red Sea marine sponge Xestospongia testudinaria. The chemical composition of the Xestospongia testudinaria methanolic extract was determined using Gas chromatography-mass spectroscopy (GC-MS) analysis. DPPH (2, 2-diphenyl-1-picryl-hydrazyl) was measured to assess the antioxidant activity of the sponge extract. Carrageenan-induced rat hind paw edema was adopted in this study. Six groups of rats were used: group1: Control, group 2: Carrageenan, group 3: indomethacin (10 mg/kg), group 4-6: Xestospongia testudinaria methanolic extract (25, 50, and 100 mg/kg). Evaluation of the anti-inflammatory activity was performed by both calculating the percentage increase in paw weight and hisopathologically. Assessment of the antioxidant and immunomodulatory activity was performed. GC-MS analysis revealed that there were 41 different compounds present in the methanolic extract. Sponge extract exhibited antioxidant activity against DPPH free radicals. Xestospongia testudinaria methanolic extract (100 mg/kg) significantly decreased % increase in paw weight measured at 1, 2, 3 and 4 h after carrageenan injection. Histopathologically, the extract caused a marked decrease in the capillary congestion and inflammatory cells infiltrate. The extract decreased paw malondialdehyde (MDA) and nitric oxide (NO) and increased the reduced glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT) activity. It also decreased the inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1 β(IL-1β) and IL-6. The results of this study demonstrated the anti-inflammatory, antioxidant, and immunomodulatory effects of the methanolic extract of the Red Sea sponge Xestospongia testudinaria (100 mg/kg).

Diabetes mellitus is regarded as a serious chronic disease that carries a high risk for considerable complications. In folk medicine, the edible Grewia asiatica fruit is used in a number of pathological conditions. This study aimed to investigate the possible curative effect of G. asiatica fruit ethanolic extract against streptozotocin- (STZ-) induced hyperglycemia in rats. Furthermore, mechanism of antihyperglycemic action is investigated. Hyperglycemic rats are either treated with 100 or 200 mg/kg/day G. asiatica fruits extract. Serum glucose, liver glycogen, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), interleukin- (IL-) 1β, and tumor necrosis factor- (TNF-) α are measured. G. asiatica fruits extract reduces blood glucose and pancreatic MDA levels. It increases liver glycogen and pancreatic GSH contents and SOD enzyme activity. Furthermore, Grewia asiatica fruits extract decreases serum IL-1β and TNF-α. The treatment also protects against STZ-induced pathological changes in the pancreas. The results of this study indicated that G. asiatica fruit extract exerts antihyperglycemic activity against STZ-induced hyperglycemia. The improvement in the pancreatic β-cells and antioxidant and anti-inflammatory effects of G. asiatica fruit extract may explain the antihyperglycemic effect.

Recent studies have demonstrated that marine sponges and their active constituents exhibited several potential medical applications. This study aimed to evaluate the possible hepatoprotective role as well as the antioxidant effect of the Red Sea Suberea mollis sponge extract (SMSE) on carbon tetrachloride- (CCl4-) induced acute liver injury in rats. In vitro antioxidant activity of SMSE was evaluated by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay. Rats were orally administered three different concentrations (100, 200, and 400 mg/kg) of SMSE and silymarin (100 mg/kg) along with CCl4 (1 mL/kg, i.p., every 72 hr) for 14 days. Plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin were measured. Hepatic malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were also measured. Liver specimens were histopathologically examined. SMSE showed strong scavenging activity against free radicals in DPPH assay. SMSE significantly reduced liver enzyme activities. Moreover, SMSE significantly reduced hepatic MDA formation. In addition, SMSE restored GSH, NO, SOD, GPx, and CAT. The histopathological results confirmed these findings. The results of this study suggested a potent protective effect of the SMSE against CCl4-induced hepatic injury. This may be due to its antioxidant and radical scavenging activity.

Recently, growing multiple uses of silymarin (SIL) as a complementary and alternative medicine, for alcohol-induced liver disease, acute and chronic viral hepatitis, as well as some other nonhepatic indications have been reported. Therefore, more attention should be paid for the hormonal side effects of SIL. Since the available data on the possible estrogenic effects of SIL is rather rare, this study aimed to further elucidate the different estrogenic effects and antiosteoporotic activity of SIL in ovariectomized (OVX) rats. OVX rats were treated chronically (12 weeks) with ethinylestradiol (EE) or SIL. Uterine and body weight were measured in all animals. Biochemical markers of bone formation (total alkaline phosphatase (ALP), calcium, phosphorus and osteocalcin), endocrinological analysis (estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH) and parathyroid hormone (PTH)) and serum total cholesterol and total lipids were estimated. Formalin fixed femora and uteri specimens were used for histopathological examination. In addition, the binding property of SIL to the two estrogen receptors (ER) subtypes was tested by molecular docking. EE (strong) and SIL (mild) stimulated uterine weight (increased uterus hyperplastic endometrial glands) but EE only prevented body weight gain following OVX. Treatment of OVX rats with both EE and SIL resulted in protection of trabecula thickness, decreased serum levels of ALP and increased serum levels of both calcium and phosphorus. In contrast to EE, SIL did not decrease OVX induced serum osteocalcin. EE not SIL decreased serum cholesterol, total lipids, LH and FSH and increased serum E2. Both EE and SIL increased serum PTH. The docking study revealed a high affinity of SIL towards ERbeta. In conclusion, findings derived in the present study presented an overview of SIL many estrogenic effects in OVX rats. SIL significantly prevents the bone loss in rats induced by OVX with mild proliferative effects in uterus. The observed effects may be due to additive beneficial effect of SIL on bone either due to direct interaction with ERbeta or increasing bone formation parameters including calcium, phosphorus, osteocalcin and PTH., (Copyright 2009 Elsevier GmbH. All rights reserved.)

Adriamycin is a potent anticancer agent, its clinical use is limited for its marked cardiotoxicity and nephrotoxicity. The present study aimed to investigate the possible protective role of the natural antioxidant silymarin on ADR-induced heart and kidney toxicity. Studies were performed on four groups of rats. 1--control group, 2--silymarin group (50 mg/kg), 3--adriamycin group (10 mg/kg), 4--adriamycin+silymarin group. On the third day after ADR injection, plasma was separated for determination of LDH, CPK, cholesterol and total lipids. 30 days after ADR injection, plasma was separated for determination of creatinine and urea levels. Frozen heart specimens (72 h) and frozen kidney specimens (30days) were used for estimation of lipid peroxides and GSH contents. Histopathological examinations of heart and kidney sections were also done. Pretreatment of ADR-treated rats with silymarin resulted in a significant decrease in the plasma CPK, LDH, creatinine and urea. On the other hand silymarin pretreatment did not change ADR-induced hyperlipidemia. Silymarin pretreatment significantly decreased the myocardial MDA contents. In addition, silymarin pretreatment normalized renal tissue contents of MDA and GSH. Histopathological examination of heart and kidney sections revealed that ADR caused only mild myocardial injury in silymarin pretreated rats. Also, silymarin pretreatment inhibited ADR-induced renal tubular damage in rats. These results have suggested that, silymarin ameliorated ADR-induced cardiotoxicity and protected against ADR-induced nephrotoxicity in male albino rats. The mechanisms of silymarin induced protection against ADR-induced toxicities were proved to be due to inhibition of lipid peroxidation and protection against GSH depletion.