Evaluation of traditionally used royal jelly (RJ) for the management of hepato-renal damage and gastrointestinal ulcerations caused by diclofenac. Forty adult male Wistar rats were allocated into four groups. Rats of the 1st group received only saline and served as normal group. The remaining 3 groups received diclofenac (50 mg/kg/day, I.P.) for 7 days. Group 2 served as diclofenac-control group. Groups 3 and 4 received RJ (150 and 300 mg/kg/day, P.O.) respectively for 30 days. Twenty-four hours after the last treatment, blood samples were collected, rats were sacrificed, and livers, kidneys, stomachs & intestines were harvested. Stomachs and intestines were tested for ulcer counts. Serum levels of AST, ALT, creatinine and urea were investigated. Hepatic, renal, gastric and intestinal tissue contents of myeloperoxidase (MPO) and prostaglandin-E2 (PGE2) were measured. Histopathological examinations were also performed followed by immunohistochemical determination of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Diclofenac administration caused significant deterioration of all the above mentioned parameters. RJ improved hepatic and renal functions. Gastric and intestinal ulcer counts were significantly ameliorated. Hepatic, renal, gastric and intestinal tissue PGE-2 contents and COX-2 expression were significantly elevated. RJ also significantly reduced MPO content and iNOS expression as compared to diclofenac-control group. Improvements of the histopathological pictures of hepatic, renal, gastric and intestinal tissues were also apparent. The study demonstrates promising protective effects of RJ against diclofenac-induced hepato-renal damage and gastrointestinal ulceration in rats.

AIM: The present study investigated the protective effect of the phytoestrogen, genistein (GEN), against (CP)-induced acute hepatotoxicity in rats.MATERIAL AND METHODS: Male adult rats were randomly assigned into five groups. Normal control group received the vehicles; CP group received a single dose of CP (200 mg/kg, i.p). The other three groups received subcutaneous GEN at doses of 0.5, 1 and 2 mg/kg/day, respectively, for 15 consecutive days prior CP injection. Sera and liver tissues were collected forty-eight hours after CP injection for assessment of liver function enzymes (ALT and AST) in rat sera, the hepatic oxidative/nitrosative biomarkers (GSH, MDA and NOx), hepatic interleukin-1β, and myeloperoxidase activity. Immunohistochemistry of cyclooxygenase-2 and histopathological examination of liver tissues were also conducted.RESULTS: The CP-induced acute liver damage was evidenced by elevated serum ALT and AST accompanied by increased hepatic oxidative stress and inflammatory biomarkers. Immunohistochemical outcomes revealed hepatic cyclooxygenase-2 expression in CP group with distortion of liver architecture. GEN-pretreatment significantly ameliorated the deterioration of liver function and exerted significant anti-oxidant and anti-inflammatory activity with a marked decline in hepatic cyclooxygenase-2 expression in a dose dependent-manner.CONCLUSION: The present study demonstrated that the antioxidant and anti-inflammatory activities of GEN might contribute to its protective effects against CP-induced liver damage.

Doxorubicin (DOX) is a standard anticancer agent exerting devastating effects as nephrotoxicity, hepatotoxicity and cardiotoxicity. The purpose of this study was to increase the clinical use of DOX through decreasing its detrimental effects via combination with ACE inhibitors to ameliorate the induced acute kidney injury (AKI). AKI was induced by a single injection of DOX (7.5 mg/kg; i.p.) as Group 1; control (vehicle), Group 2; DOX (7.5 mg/kg; i.p.) single dose, Group 3 and 4; Lisinopril (Lis, 20 mg/kg) and Enalapril (Enal, 40 mg/kg) orally administration for 15 consecutive days after DOX injection, respectively. Serum samples were used to measure creatinine and BUN, tissue samples were extracted to determine myeloperoxidase (MPO), malondialdehyde (MDA), total antioxidant capacity (TAC) and kidney injury molecule (KIM-1) using ELISA technique. Heme oxygenase (HO-1) RNA expression was quantified in tissue using real time polymerase chain reaction (PCR). Parts of the kidney tissue were kept in formalin for immunohistochemical demonstration of Cleaved Caspase-3 and NF-κβ immune staining and the other part was used for pathological examination. Oral treatment with Lis (20 mg/kg) and Enal (40 mg/kg) for 15 consecutive days reversed DOX effects as they reduced the serum creatinine and BUN, kidney levels of MPO and MDA, whereas the drugs increased tissue TAC. The administration of Lis and Enal with DOX also reduced KIM-1and HO-1 RNA expression. A significant decrease in cleaved caspase-3 and NF-κβ immunostainings in conjunction with pronounced amelioration in pathologies in the rat kidney were observed. We concluded that DOX adverse effects can be controlled by Lis and Enal.

Migraine is one of the major symptoms of many psychiatric and mental disorders like depression and anxiety. Eletriptan Hydrobromide (EH) is a well-tolerated drug in migraine treatment, but suffers from low oral bioavailability and low brain targeting after oral delivery. New nasal mucoadhesive EH-emulsomes development could be a new means to direct the drug from the nose-to-brain to achieve rapid onset of action and high drug concentration in the brain for acute migraine treatment. Eletriptan mucoadhesive emulsomes formulations were prepared using thin-film hydration method and 2³ full factorial design was adopted to study different formulation factors’ effect on the emulsomes characters. The emulsomes were characterized for entrapment efficiency (EE%), zeta potential (ZP), particle size (PS), morphology, and ex-vivo permeation through the nasal mucosa. The selected formula was evaluated in mice for its in-vivo bio-distribution in comparison with EH intranasal and intravenous solutions. Drug targeting efficacy (DTE%) and nose-to-brain direct transport percentage (DTP%) were calculated. The optimization formulation showed a nanoparticle size of 177.01 nm, EE 79.44%, and ZP = 32.12 ± 3.28 mV. In addition, in-vitro permeability studies revealed enhanced drug permeability with suitable mean residence time up to 120 ± 13 min. EH-emulsomes were stable under different storage conditions for three months. In vivo examination and pharmacokinetic drug targeting parameters revealed EH transport to the CNS after EH nanoparticle nasal administration. Histopathology study showed no ciliotoxic effect on the nasal mucosa. From the results, it can be confirmed that the emulsomes formulation of EH proved safe direct nose-to-brain transport of EH after nasal administration of EH emulsomes.

Cisplatin (CP) is a powerful antineoplastic chemotherapeutic agent with broad-spectrum properties. Acute and cumulative cardiotoxicity are major limiting factors for CP therapy. Various pathogenic pathways have been suggested to CP-induced cardiotoxicity; oxidative damage, ER stress, and programmed cell death/apoptosis. The present study aimed to assess the signaling mechanisms related to the advantageous effects of rosuvastatin (RSV) and simvastatin (SMV) against CP-related cardiac ER stress dependent apoptotic death in rats. Acute cardiotoxicity was induced by a single dose of CP (10 mg/kg, i.p.) on the 10th day of the experiment. RSV (10 mg/ kg/day) and SMV (10 mg/kg/day) were orally administered for 15 days. CP-treated rats showed significant alterations in electrocardiographic recordings and elevation in serum cardiac function biomarkers; troponin T content, lactate dehydrogenase and creatine kinase-MB levels as well as boost in the cardiac oxidative stress biomarkers. In addition, CP exposure resulted in GRP78 induction; an ER stress and elevation marker at calpain-1 content as well as activation of activated caspase-3 (ACASP3) and caspase-12 were reflected on CP-triggered apoptosis evidenced by elevation in the Bax/Bcl-2 ratio. However, RSV and SMV administration mitigate those adverse CP effects. Statins administration prominently alleviated CP-induced cardiac abnormalities exerting improvement in the ECG pattern and cardiac enzyme biomarkers. Interestingly, statins; RSV and SMV, disrupted CP-induced ER stress and the consequent apoptotic cell death evidenced by downregulation of ER-chaperone GRP78, calpain-1, ACASP3 and caspase-12 as well as decline in the Bax/Bcl-2 ratio. From all the previous findings, it can be suggested that statins namely; RSV and SMV, play protective role against CP-induced cardiac injury by regulating ER stress-mediated apoptotic pathways.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that ultimately occurs as a complication of acute or chronic liver failure; accompanied by hyperammonemia. This study aimed to evaluate the potential of biopropolis as a hepato- and neuro-protective agent using thioacetamide (TAA)-induced acute HE in rats as a model. Sixty Wistar rats were divided into 5 groups: Group 1 (normal control) received only saline and paraffin oil. Group 2 (hepatotoxic control) received TAA (300 mg/kg, once). Groups 3, 4, and 5 received TAA followed by vitamin E (100 mg/kg) and biopropolis (100 and 200 mg/kg), respectively, daily for 30 days. Evidences of HE were clearly detected in TAA-hepatotoxic group including significant elevation in the serum level of ammonia, liver functions, increased oxidative stress in liver and brain, apoptotic DNA fragmentation and overexpression of iNOS gene in brain tissue. The findings for groups administered biopropolis, highlighted its efficacy as a hepato- and neuro-protectant through improving the liver functions, oxidative status and DNA fragmentation as well as suppressing the brain expression of iNOS gene. In conclusion, biopropolis, at a dose of 200 mg/kg per day protected against TAA-induced HE through its antioxidant and antiapoptotic influence; therefore, it can be used as a protective natural product.