THE IMPACT OF NEW TARGETING METHODS IN THE CANCER THERAPY

Rapid development has achieved in treating tumor to stop malignant cell growth and metastasis in the past decade. Numerous researches have emerged to increase potency and efficacy with novel methods for drug delivery. The main objective of this literature review was to illustrate the impact of current new targeting methods to other previous delivering systems to select the most appropriate method in cancer therapy. This review first gave a brief summary of cancer structure and highlighted the main roles of targeting systems. Different types of delivering systems have been addressed in this literature review with focusing on the latest carrier derived from malarial protein. The remarkable advantages and main limitations of the later have been also discussed. PubMed and Science Direct were the main search engines that have been used as information sources to prepare this review. Articles related to cancer targeting system, active and passive processes, current nanoparticles, antibody carriers, and current novel cancer carriers were used as sources in this review. Important points from many references published in the last decade (2008-2018) were selected and included. Several targeting methods were introduced to enhance the efficacy and tolerability of the toxic drug by active and passive processes, but there is still no conclusive carrier without certain drawbacks. A combination of targeting methods probably shows the most appropriate choice for increasing selectivity and safety of anticancer drugs via reducing the concentration of carriers used

Ameliorating Effect of Oral Guggulsterone Administration in Imiquimod-Induced Psoriasis in Mice

Psoriasis is a common chronic skin condition characterized by infiltration of inflammatory cells into the epidermis and altered keratinocyte differentiation. In this work, psoriasis was induced by an imiquimod 5% cream, an immune response modifier that can induce psoriasis-like skin inflammation when applied topically in mice. Guggulsterone prepared as a suspension and has been orally given to mice before imiquimod application. The results of the current study showed that guggulsterone suspension can significantly reduce psoriasis area and severity index in (guggul suspension+imiquimod group as compared with both control group and (vehicle suspension+imiquimod ) group

Berbamine and thymoquinone exert protective effects against immune-mediated liver injury via NF-κB dependent pathway

BackgroundImmune-mediated hepatitis is a severe impendence to human health, and no effective treatment is currently available. Therefore, new, safe, low-cost therapies are desperately required. Berbamine (BE), a natural substance obtained primarily from Berberis vulgaris L, is a traditional herbal medicine with several bioactivities, such as antimicrobial and anticancer activities. Thymoquinone (TQ), a phytochemical molecule derived from the Nigella sativa plant's black cumin seeds, has attracted interest owing to itsanti-inflammatory, antioxidant, and anticancer properties.AimThis current study's aims was to examine the protective impacts of BE and TQ in Concanavalin A (ConA)- induced acute liver injury and the action's underlying mechanism.Methodssixty mice of both sexes were used and divided into four groups (each group with six mice) as follows: Group I obtained distilled water (negative control group). Group II received distilled water with a single dose of 0.1 ml ConA (20 mg/kg) on day 4 by retro-orbital route (model group). Groups III and IV received BE (30 mg/kg/day) and TQ (25 mg/kg/day), respectively, by oral gavage for four successive days, with a single dose of ConA (20 mg/kg) on day 4, then all animals were sacrificed after 8 h and prepared for liver and blood collection.ResultsConA administration increased the ALT, AST, TNF-α, INFγ, and NF-κB significantly (p < 0.001) in the model group. Both BE and TQ could reduce these parameters significantly (p < 0.001) in groups III and IV, respectively, compared to the model group.ConclusionBoth BE and TQ prominently attenuated ConA immune-mediated liver injury. These findings give a remarkable insight into developing a new therapeutic agent for treating hepatitis and other autoimmune diseases

Protective Effects of Safranal Against Selenite-Induced Cataract in Rats

Cataract, which is the opacity inside clear ocular lens of eye, result in the scattering of visible light as it passes via the lens and consequently deterioration in optical image. The aim of the present study was to investigate whether safranal, an active constituent of Crocus sativus L. stigmas, has a protective effect on the cataract in the rat's pups. The animals were randomly divided into five groups, each of which consisted of 7 rat pups. Group I served as normal control (vehicle administration). For testing cataract induction, animals of Groups II, III, and IV were administered a single subcutaneous injection of sodium selenite on postpartum day 12. After sodium selenite intoxication, Group II served as control selenite, Groups III-IV received intraperitoneal safranal at doses of 200, and 300 mg/kg, respectively from the 11th day through the 17th day, while group V receive only safranal (300 mg/kg). On postpartum day 30, the rat pups were examined for cataract formation, and the lenses were isolated for further analysis. This study found that selenite caused significant (p < 0.05) cataract formation. Through the effects of selenite on the level of lipid peroxidation (MDA) which was upregulated. Furthermore, the antioxidant enzymes levels GSH levels and NRF2 protein were downregulated. In contrast, treatment with safranal could significantly (p < 0.05) ameliorate cataract formation and oxidative damage in the lens. Moreover, safranl administration significantly increased the protein expressions of Nrf2 and the GSH level, in addition to reducing the level both the MDA and the level soluble proteins in the lens. Taken together, safranal is a prospective anti-cataract agent that probably delays the onset and progression of cataracts induced by sodium selenite

Assessment of ellagic acid action in 5-fluorouracil induced intestinal mucositis

The intestinal mucositis define as inflammation and ulceration in the gastrointestinal tract wall and in some case in the oral cavity these cause by treatment with antineoplastic drug like 5-fluorouracil and Irinotecan and other types of chemotherapeutics drugs , 5-Fluorouracil-induced intestinal mucositis (IM) is consider as one of the more common tumor issue .it cause series of undesirables symptoms like severe diarrhea ,abdominal pain , stomach uncomfortable and other. The aim of this current study to see how ellagic acid act to  Attenuates 5-FU-Induced Intestinal Mucositis and  Diarrhea in Mice . we induced the intestinal mucositis by injected the mice intraperitoneally in 5-fluorouracil about 50mg per kg daily for four days respectively and then assessment the IM by measurement the level of some antioxidant enzymes like SOD , and level of some pro-inflammatory cytokines (IL-6) and lipid peroxidation biomarker (MDA) and we note the difference in the histopathological scoring after administration the ellagic acid to the mice in two different dose (10mg and 5mg per kg) daily for ten days respectively and before the fluorouracil injection  in one hour .pretreatment with ellagic acid specialized dose of 10mg per kg significant improvement in the level of antioxidant enzymes ,pro inflammatory cytokines ,lipid peroxidation biomarker and histopathologicaL score  compared with 5-FU group, moreover the potential action of ellagic acid was further supported by histopathological examination. all these data suggest that the ellagic acid effective in protective from 5-FU-induced intestinal mucositis

Possible Protective Effect of Low Dose of Papaverine on ANIT Induce Cholestasis in Rat

Abstract Intrahepatic cholestasis is clinical syndrome which cause either by defect in synthesis or bile acid flow, the pathophysiology of cholestasis is complicated by a number of  variables, including oxidative stress, inflammatory response, and  dysregulation of bile acid transporter . Rats, mice, and guinea pigs were utilized as experimental animals, and ANIT was administered to them in order to create a model that closely resembled intrahepatic cholestasis in human. This study examined the protective effects of papaverine, a non-narcotic opium alkaloid derived from papaver somniferum and discovered as an FXR agonist, on cholestasis in rats induced by alpha-naphthylisothiocyanate (ANIT). Rats utilized in this study divided  into 3 groups (10 rats per each groups), group I (control) or vehicle group  rat administered corn oil (1ml/kg) once daily 48 hour before sacrifice group II rats orally administered alpha-naphthylisothiocyanate (ANIT) 100mg/kg single dose 48hour before sacrifice  group III rats administered 100mg/kg papaverine orally  for 7 consecutive days and  at day 5  rat administered alpha-naphthylisothiocyanate (ANIT) The results showed that papaverine treatment decreased alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin, total bile acid, as well as increased antioxidant enzyme GPX and decreased MDA and inflammatory mediators tumor necrosis factor TNF- and interleukin IL1-β. In conclusion, papaverine may have a protective effect to alleviate ANIT-induced cholestasis and may be a therapeutic target to treat cholestasis

Serum Level Profile and Pharmacokinetic Parameters of Single Oral Dose of Metronidazole in Type II Diabetic Patients

Many pathophysiological processes can affect the pharmacokinetic properties of drugs in people with diabetes. The present study was deigned to evaluate the influence of diabetes mellitus (DM) on the pharmacokinetic parameters of metronidazole administered as single oral dose. Twelve healthy volunteers and twelve diabetic patients were enrolled in the present study. On day 1, a single oral dose of metronidazole 500 mg was administered orally to all participants at 9:00 am after a 10-hour fasting. Over the following 48 hours, blood samples were taken at frequent intervals and serum metronidazole concentrations were measured by a high-performance liquid chromatography method for assessment of pharmacokinetics of metronidazole. The data indicated that maximum serum concentration (Cmax) and Kelim were significantly decreased (P<0.05) in diabetic patients compared with that reported in healthy subjects (25.73% and 31.51% respectively). Meanwhile, the values of time to reach maximum peak (Tmax), AUClast, AUCtotal, and half life (T½) were significantly increased (P<0.05) compared with those reported in healthy subjects (20.69%, 33.65%, 30.13%, and 20.689% respectively). In conclusion, diabetes mellitus affects some of the pharmacokinetics values of orally administered metronidazole. Key words: Diabetes mellitus , Metronidazole, Pharmacokinetic, Serum Leve