Cisplatin-based combination therapy for cancer.

Cisplatin, that is, cis-diamminedichloroplatinum is a coordinate compound that is mainly preferred as prior treatment against several solid tumors and malignancies like ovaries, head and neck, testicular, and lung cancers because of its anticancer activity. Cisplatin binds at the N7 position of purine and forms adducts, leading to altered activity of DNA that triggers apoptosis. DNA damage is followed by several signaling pathways like induced oxidative stress, upregulated p53, mitogen-activated protein kinase (MAPK), and Jun N-terminal kinases (JNK) or Akt pathways along with induced apoptosis. Additionally, cisplatin treatment comes with few disadvantages such as toxic effects, that is, hepatotoxicity, cardiotoxicity, neurotoxicity, etc., and drug resistance. Furthermore, to overcome cisplatin resistance and toxicological effects, combination drug therapy has been considered. The aim of the review is to focus on the molecular mechanism of action of cisplatin and combination drug therapy to reduce the side effects in cancer therapy.

Applications of Adductomics in Chemically Induced Adverse Outcomes and Major Emphasis on DNA Adductomics: A Pathbreaking Tool in Biomedical Research.

Adductomics novel and emerging discipline in the toxicological research emphasizes on adducts formed by reactive chemical agents with biological molecules in living organisms. Development in analytical methods propelled the application and utility of adductomics in interdisciplinary sciences. This review endeavors to add a new dimension where comprehensive insights into diverse applications of adductomics in addressing some of society's pressing challenges are provided. Also focuses on diverse applications of adductomics include: forecasting risk of chronic diseases triggered by reactive agents and predicting carcinogenesis induced by tobacco smoking; assessing chemical agents' toxicity and supplementing genotoxicity studies; designing personalized medication and precision treatment in cancer chemotherapy; appraising environmental quality or extent of pollution using biological systems; crafting tools and techniques for diagnosis of diseases and detecting food contaminants; furnishing exposure profile of the individual to electrophiles; and assisting regulatory agencies in risk assessment of reactive chemical agents. Characterizing adducts that are present in extremely low concentrations is an exigent task and more over absence of dedicated database to identify adducts is further exacerbating the problem of adduct diagnosis. In addition, there is scope of improvement in sample preparation methods and data processing software and algorithms for accurate assessment of adducts.

Combination of daidzein, hemin and bms182874 halts the progression of diabetes-induced experimental nephropathy.

The present study has been designed to investigate the combined effect of daidzein (caveolin inhibitor), hemin (hemoxygenase activator) and BMS182874 (endothelin receptor antagonist) in diabetic nephropathy in wistar rats. Diabetic nephropathy was induced by administering single dose of streptozotocin in wistar rats. DN was clinically assessed by the estimation of various biochemical parameters and histopathological studies of renal tissue. DN was assessed by measuring serum creatinine, blood urea nitrogen, proteinuria, renal cortical collagen content, lipid profile, serum nitrite/nitrate ratio, renal TBARS and reduced glutathione levels. The combination of daidzein, hemin and BMS182874 showed significant improvement in (BUN, serum creatinine, proteinuria, urinary output, kidney weight/ body weight, renal cortical collagen content, nitrite/ nitrate level, renal TBARS, reduced glutathione) renal parameters studied for DN in comparison with single drug administration as well as a combination of two drugs. L-NAME (NG-nitro- L-arginine methyl ester) a selective eNOS inhibitor abolished the ameliorative effect of combination of daidzein, hemin and BMS182874 in DN in rats. It may therefore be concluded that Daidzein in combination with hemin may enhance the level of renal nitric oxide by decreasing the expression of caveolin. BMS182874 shows renoprotection by inhibiting RAAS system and through reactivation of NO synthesis. These findings may provide mechanistic insights to explain renoprotective effect of this combined therapy in diabetes.