Using an active targeting approach of chemotherapeutics-loaded nanocarriers (NCs) with monoclonal antibodies is a potential strategy to improve the specificity of the delivery systems and reduce adverse reactions of chemotherapeutic drugs. Specific targeting of the human epidermal growth factor receptor-2 (HER-2), expressed excessively in HER-2-positive breast cancer cells, can be achieved by conjugating NCs with an anti-HER-2 monoclonal antibody. We constructed trastuzumab-conjugated chitosan iodoacetamide-coated NCs containing doxorubicin (Tras-Dox-CHI-IA-NCs) as a tumor-targeted drug delivery system, during the study. Chitosan-iodoacetamide (CHI-IA) was synthesized and utilized to prepare trastuzumab-conjugated NCs (Tras-NCs). The morphology, physicochemical properties, drug loading, drug release, and biological activities of the NCs were elucidated. The Tras-NCs were spherical, with a particle size of approximately 76 nm, and had a positive zeta potential; after incorporating the drug, the size of the Tras-NC increased. A prolonged, 24-h drug release from the NCs was achieved. The Tras-NCs exhibited high cellular accumulation and significantly higher antitumor activity against HER-2-positive breast cancer cells than the unconjugated NCs and the drug solution. Therefore, Tras-Dox-CHI-IA-NCs could be a promising nanocarrier for HER-2-positive breast cancer.
- MeSH
- Chitosan * chemistry MeSH
- Doxorubicin chemistry MeSH
- Iodoacetamide MeSH
- Drug Delivery Systems MeSH
- Humans MeSH
- Antibodies, Monoclonal chemistry MeSH
- Breast Neoplasms * drug therapy MeSH
- Nanoparticles * chemistry MeSH
- Drug Carriers chemistry MeSH
- Trastuzumab MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Oxidative stress and NF-κB signaling plays a major role in pathogenesis of osteoarthritis. In the present study, we analyzed the potent role of carnosol against osteoarthritis in cells treated using monosodium iodoacetate (MIA) model through in vitro studies. MIA caused dose-dependent cell death and induced programmed cell death by increasing subG1 accumulation and caspase-3 expressions. MIA caused oxidative stress by increasing reactive oxygen species, lipid peroxidation and further induced NF-κB expression and down regulated Nrf-2 levels. Pre-treatment with carnosol significantly protected the cells by reducing the oxidative stress markers and improved the cell viability up to 98%. Further, carnosol down regulated NF-κB nuclear expression with a concomitant increase in Nrf-2 nuclear localization and up regulated the nuclear Nrf-2 levels. Carnosol also inhibited MIA-induced subG1 accumulation and caspase-3 activation. This study demonstrates that, carnosol might act as potent antioxidant and regulate MIA-induced oxidative stress, NF-κB signaling and programmed cell death by up regulating the Nrf-2 levels.
- MeSH
- Antioxidants metabolism MeSH
- Apoptosis drug effects MeSH
- Chondrocytes pathology drug effects MeSH
- Cartilage MeSH
- Abietanes pharmacology metabolism therapeutic use MeSH
- NF-E2-Related Factor 1 administration & dosage MeSH
- Iodoacetates pharmacology adverse effects MeSH
- Cells, Cultured MeSH
- NF-kappa B antagonists & inhibitors MeSH
- Osteoarthritis * metabolism physiopathology MeSH
- Oxidative Stress drug effects MeSH
- Rats, Sprague-Dawley MeSH
- Reactive Oxygen Species antagonists & inhibitors MeSH
- Inflammation genetics chemically induced physiopathology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
Knowledge on the involvement of spinal COX-1 and COX-2 in pain due to osteoarthritis could be useful for better understanding of its pathogenesis and therapy. In this study we have investigated a long-term pattern of expression and production of spinal COX-1 and COX-2 in the model of osteoarthritis induced in rats by injection of monoiodoacetate (MIA) into the knee joint. MIA injection produced thermal hyperalgesia (assessed by the plantar test) and tactile allodynia (measured with von Frey hairs). The pain measures reached maximum on the fifht day, then remained relatively stable. The expression of spinal COX-2 mRNA reached maximum on day 5 (5.2 times; P<0.001) and remained increased until day 31 (4.9 times; P<0.001). Expression of spinal COX-1 mRNA increased gradually reaching maximum on the day 31 (4.5 times; P<0.001) when the relative expression of both genes was almost equal. The production of both proteins was almost similar at the beginning of the experiment. The highest production of COX-2 protein was observed on day 5 after the induction of osteoarthritis (increased 3.9 times). The levels of COX-1 protein increased gradually with maximum on day 31 (3.4 times). The present findings indicate that not only expression of COX-2 mRNA but also that of COX-1 mRNA is significantly increased in the spine during osteoarthritis pain. Thus, in contrast to inflammatory pain, the upregulation of spinal COX-1 may be important in osteoarthritis pain.
- MeSH
- Osteoarthritis, Knee enzymology genetics chemically induced MeSH
- Pain epidemiology genetics chemically induced MeSH
- Time Factors MeSH
- Cyclooxygenase 1 biosynthesis genetics MeSH
- Cyclooxygenase 2 biosynthesis genetics MeSH
- Enzyme Induction MeSH
- Financing, Organized MeSH
- Hyperalgesia enzymology genetics chemically induced MeSH
- Rats MeSH
- Iodoacetic Acid MeSH
- Membrane Proteins biosynthesis genetics MeSH
- Pain Measurement MeSH
- RNA, Messenger MeSH
- Spinal Cord enzymology MeSH
- Disease Models, Animal MeSH
- Rats, Wistar MeSH
- Pain Threshold MeSH
- Reaction Time MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
Byl testován vliv kyseliny jodoctové ve 4 různých koncentracích na produkci flavonoidů v kalusové a suspenzní kultuře Ononis arvensis L. Elicitor byl v kontaktu s kulturou po dobu 6; 24; 48; 72 a 168 hodin. Z dosažených výsledků vyplývá statisticky významný nárůst obsahu flavonoidů v suspenzní kultuře oproti kontrole při použití všech testovaných koncentrací elicitoru, a to po 6; 24; 48 a 72 hodinové elicitaci. Maximální zvýšení produkce flavonoidů v suspenzní kultuře nastalo při použití kyseliny jodoctové v koncentraci 1 mg/l, a to o 586 %. U kalusové kultury došlo k maximálnímu zvýšení tvorby flavonoidů při použití kyseliny jodoctové v koncentraci 10 mg/l a po 24 hodinách elicitace, obsah flavonoidů byl zvýšen o 529 % oproti kontrole.
The paper tested the effect of iodoacetic acid in four different concentrations on the production of flavonoids in the callus and suspension culture oi Ononis arvensis L. The elicitor was in contact with the culture for a period of 6; 24; 47; 72, and 168 hours. The obtained results show a statistically significant increase in the content of flavonoids in the suspension culture in comparison with the control in the use of all tested concentrations of the elicitor after 6; 24; 48, and 72 hours of ehcitation. The maximal increase by 586 % in the production of flavonoids in the suspension culture took place with the use of iodoacetic acid in a concentration of 1 mg/l. In the callus culture, the maximal increase in the formation of flavonoids occurred with the use iodoacetic acid in a concentration of 10 mg/l after 24 hours of elicitation, the content of flavonoids being increased by 529 % in comparison with the control.
- MeSH
- Alanine pharmacology MeSH
- Antimetabolites pharmacology MeSH
- Chloromercuribenzoates pharmacology MeSH
- Cycloserine pharmacology MeSH
- Dinitrophenols pharmacology MeSH
- Fibroblasts metabolism MeSH
- Interferons biosynthesis MeSH
- Iodoacetates pharmacology MeSH
- Culture Techniques MeSH
- Chick Embryo MeSH
- Orthomyxoviridae pathogenicity MeSH
- Serine pharmacology MeSH
- Sodium pharmacology MeSH
- Stereoisomerism MeSH
- Animals MeSH
- Check Tag
- Chick Embryo MeSH
- Animals MeSH
- MeSH
- Alanine pharmacology MeSH
- Antimetabolites pharmacology MeSH
- Chloromercuribenzoates pharmacology MeSH
- Cycloserine pharmacology MeSH
- Dinitrophenols pharmacology MeSH
- Fibroblasts metabolism MeSH
- Interferons biosynthesis MeSH
- Iodoacetates pharmacology MeSH
- Culture Techniques MeSH
- Chick Embryo MeSH
- Orthomyxoviridae pathogenicity MeSH
- Serine pharmacology MeSH
- Sodium pharmacology MeSH
- Stereoisomerism MeSH
- Animals MeSH
- Check Tag
- Chick Embryo MeSH
- Animals MeSH
- MeSH
- Immune Sera MeSH
- Antibody-Producing Cells metabolism radiation effects MeSH
- Time Factors MeSH
- Erythrocytes immunology MeSH
- Histological Techniques MeSH
- Immunization MeSH
- Immunoglobulin G analysis biosynthesis MeSH
- Immunoglobulin M analysis biosynthesis MeSH
- Injections, Intravenous MeSH
- Iodoacetates MeSH
- Complement System Proteins MeSH
- Guinea Pigs MeSH
- Mice MeSH
- Sheep MeSH
- Polysaccharides MeSH
- Radiation Effects MeSH
- Spleen MeSH
- Antibody Formation MeSH
- Freezing MeSH
- Animals MeSH
- Check Tag
- Guinea Pigs MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- MeSH
- Dinitrophenols pharmacology MeSH
- Potassium pharmacology MeSH
- Fluorides pharmacology MeSH
- Glucose MeSH
- Glycerophosphates MeSH
- Iodoacetates pharmacology MeSH
- Rats MeSH
- Ketoglutaric Acids pharmacology MeSH
- Norepinephrine antagonists & inhibitors pharmacology MeSH
- Sodium pharmacology MeSH
- Oxygen Consumption drug effects MeSH
- Succinates MeSH
- Drug Synergism MeSH
- Adipose Tissue metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- MeSH
- Retinal Degeneration enzymology chemically induced physiopathology pathology MeSH
- Electroretinography MeSH
- Fluorides MeSH
- Glyceraldehyde-3-Phosphate Dehydrogenases metabolism MeSH
- Histocytochemistry MeSH
- Iodoacetates MeSH
- Rabbits MeSH
- L-Lactate Dehydrogenase metabolism MeSH
- Humans MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Humans MeSH
- Animals MeSH
