Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

While medicinal inorganic chemistry has been practised for over 5000 years, it was not until the late 1800s when Alfred Werner published his ground-breaking research on coordination chemistry that we began to truly understand the nature of the coordination bond and the structures and stereochemistries of metal complexes. We can now readily manipulate and fine-tune their properties. This had led to a multitude of complexes with wide-ranging biomedical applications. This review will focus on the use and potential of metal complexes as important therapeutic agents for the treatment of cancer. With major advances in technologies and a deeper understanding of the human genome, we are now in a strong position to more fully understand carcinogenesis at a molecular level. We can now also rationally design and develop drug molecules that can either selectively enhance or disrupt key biological processes and, in doing so, optimize their therapeutic potential. This has heralded a new era in drug design in which we a...

Toward Multi-Targeted Platinum and Ruthenium Drugs-A New Paradigm in Cancer Drug Treatment Regimens?

Nonenzymatically glycated human serum albumin and glycated poly-lysine(Lys) in vitro brought about the reduction of nitroblue tetrazolium and ferricytochrome c at pH 9.06 and pH 7.8, respectively. This reduction was inhibited partially by superoxide dismutase (SOD). Glycated poly-Lys caused the oxidation of NADH in the presence of LDH at pH 7.0 which was completely inhibited by SOD. Glycated material was found to function both as a reductant and an oxidant. The reactivity of glycated material is discussed and a possible mechanism by which superoxide is produced is proposed. Results may give a clue to diabetic complications.

Superoxide production from nonenzymatically glycated protein

Tumor microenvironment as a therapeutic target in cancer

Inflammation is associated with the development and malignant progression of most cancers. As most of the cell types involved in cancer-associated inflammation are genetically stable and thus are not subjected to rapid emergence of drug resistance, the targeting of inflammation represents an attractive strategy both for cancer prevention and for cancer therapy. Tumor-extrinsic inflammation is caused by many factors, including bacterial and viral infections, autoimmune diseases, obesity, tobacco smoking, asbestos exposure, and excessive alcohol consumption, all of which increase cancer risk and stimulate malignant progression. In contrast, cancer-intrinsic or cancer-elicited inflammation can be triggered by cancer-initiating mutations and can contribute to malignant progression through the recruitment and activation of inflammatory cells. Both extrinsic and intrinsic inflammation can result in immunosuppression, thereby providing a preferred background for tumor development. In clinical trials, lifestyle modifications including healthy diet, exercise, alcohol, and smoking cessation have proven effective in ameliorating inflammation and reducing the risk of cancer-related deaths. In addition, consumption of certain anti-inflammatory drugs, including aspirin, can significantly reduce cancer risk, suggesting that common nonsteroidal anti-inflammatory drugs (NSAID) and more specific COX2 inhibitors can be used in cancer prevention. In addition to being examined for their preventative potential, both NSAIDs and more potent anti-inflammatory antibody-based drugs need to be tested for their ability to augment the efficacy of more conventional therapeutic approaches on the basis of tumor resection, radiation, and cytotoxic chemicals. Cancer Prev Res; 9(12); 895-905. ©2016 AACR.

https://cancerpreventionresearch.aacrjournals.org/content/canprevres/9/12/895.full.pdf

Targeting Inflammation in Cancer Prevention and Therapy

http://www.if-pan.krakow.pl/pjp/pdf/2010/2_233.pdf

COX-2 as a target for cancer chemotherapy.

Lymphocyte infiltration into the intestinal tract in inflammatory bowel disease (IBD) is mediated by interaction between α4 integrin and its specific ligands. Development of monoclonal antibodies against α4 integrin allowed targeting of lymphocyte trafficking into the intestine as a novel therapeutic intervention. Natalizumab, vedolizumab, alicaforsen AJM300, rhuMAb β7, CCX282-B, and PF-00547,659 are few of monoclonal antibodies that have shown high promise in trials with the potential for more attractive benefit:risk ratio than currently available therapies. In this review, an attempt is made to underline the therapeutic potential and the safety of anti-adhesion molecule treatment in IBD.

Inhibition of selective adhesion molecules in treatment of inflammatory bowel disease.

Current advances in understanding of the pathogenesis of inflammatory bowel disease have encouraged the development of many new therapies targeted at specific and non-specific mediators of the inflammatory bowel disease inflammatory pathway. Crohn's disease and ulcerative colitis, two common inflammatory bowel diseases likely result from interaction of multiple genetic and environmental risk and protective factors, deregulation of mucosal immunity in gut and breakdown of delicate balance of proinflammatory and anti-inflammatory cytokines. Immunobiologic agents targeted against TNF, leukocyte adhesion, Th1 polarization, T cell activation, nuclear factor-kappaB (NF-kappaB), and others are being assessed and will open exciting perspectives on development of therapies for inflammatory bowel disease.

Mechanisms and efficacy of immunobiologic therapies for inflammatory bowel diseases.

Hepatoprotective activity of the methanol extract of Litsea glutinosa (MELG) was investigated by inducing hepatotoxicity with CCl4 and paracetamol in rats. Increased levels of biochemical parameters like aspartate transaminase, alanine transaminase, bilirubin and alkaline phophatase in serum, along with reduced activity of catalase and super oxide dismutase in liver were induced by paracetamol and CCl4. Hepatic tissue architecture was also distorted by the hepatotoxins. Oral administration of MELG (100-200 mg/kg) offered a significant dose dependent protection against paracetamol and CCl4 induced hepatotoxicity and restored the levels of the biochemical parameters to control levels. The hepatoprotective activity of MELG against paracetamol and CCl4 was comparable with silymarin, which was used as reference standard. The results of this study indicate that MELG has potent hepatoprotective action against paracetamol and CCl4 induced hepatic damage in rats.

Hepatoprotective activity of methanol extract of Litsea glutinosa against hepatotoxin induced toxicity

Diabetes mellitus (DM) is a chronic metabolic disorder that is affecting the worldwide population with high rates of morbidity and mortality. The most prevalent case of DM is type 2 diabetes mellitus (T2DM) which is characterized by insulin resistance and insulin secretion defect due to impaired β-cell functioning. Epidemiological studies implied that the number of diabetic cases has been doubled during the past two decades and has turned out to be a global epidemic accompanied by severe metabolic and endocrine complications over time. The rising emergence of T2DM in children, adolescents, and young adults signifies it to be one of the most dominant perturbing features of its kind. Proper diet control, moderate exercise, and hypoglycemic and lipid-lowering agents are some evident strategies that have been employed in the management of T2DM so far. However, a distinct possibility of severe diabetic complications still exists despite the therapeutic benefits achieved by these drugs. Various in vitro and in vivo models have suggested that phytochemicals exert several pharmacological effects on metabolic disorders such as in hyperglycemia, hypertension, and hyperlipidemia by modulating oxidative stress, inflammatory response, autophagy, and anti-apoptosis effects. Additionally, they have positive modulatory actions on molecular targets of T2DM like insulin signaling, IRS, glucose transporters, α-glucosidase, PPARγ, DPP-IV, PTP1B, NF-κB, etc. Regulation of these maladaptive pathophysiological mechanisms can improve insulin-resistant state, lower blood glucose levels, and protect against various macrovascular and microvascular complications. Thus, natural products have garnered significant interest as bioactive agents in the management of T2DM. This chapter aims to overview the activities and underlying mechanisms of natural medicine in the management of T2DM.

Rituparna Chaki

Papers

COX-2 as a target for cancer chemotherapy.

Inhibition of selective adhesion molecules in treatment of inflammatory bowel disease.

Mechanisms and efficacy of immunobiologic therapies for inflammatory bowel diseases.

Hepatoprotective activity of methanol extract of Litsea glutinosa against hepatotoxin induced toxicity

Pharmacology and Mechanisms of Natural Medicine in Treatment of Type 2 Diabetes Mellitus