Protective effects of tocotrienols against lipid-induced nephropathy in experimental type-2 diabetic rats by modulation in TGF-β expression

Dyslipidemia is common in patients with diabetes mellitus (DM) and is considered a risk factor for the progression of diabetic nephropathy (DN). Hyperlipidemia and hyperglycemia act synergistically to induce renal injury. The present study was designed to investigate the protective effects of tocotrienols as tocotrienol-rich fraction (TRF) extracted from palm (PO) and rice bran oils (RBO) against lipid induced nephropathy in type-2 diabetic rats and its probable molecular mechanism. Male Wistar rats (175–200 g) were divided into four groups. The first group served as diabetic control, while the second and third groups received PO-TRF and RBO-TRF, respectively by gavage over a period of sixteen weeks post-induction of diabetes. The fourth group comprised of age-matched rats that served as normal control. The effects of TRF on serum lipid profile, oxidative stress markers, expression of TGF-β, fibronectin and collagen type IV were analyzed in the kidney of diabetic rats. Treatment with PO-TRF and RBO-TRF significantly improved glycemic status, serum lipid profile and renal function in type-2 diabetic rats. In addition, TRF supplementation down-regulated the expression of TGF-β, fibronectin and collagen type IV in the kidney of diabetic rats. Transforming growth factor-β (TGF-β) plays a critical role in progression of DN, but its modulation by tocotrienols in DN remains unexplored. TRF ameliorated lipid induced nephropathy in type-2 diabetes by its hypoglycemic, hypolipidemic and antioxidant activities as well as by modulation of TGF-β to prevent increased expression of collagen type IV and fibrinogen. We finally propose a mechanism for the expression of molecular markers that are significant in the events leading to diabetic nephropathy and its modulation by tocotrienols/TRF.     

Novel anti-thrombotic therapy in acute coronary syndromes

Despite recent developments in revascularisation, anti-platelet and anti-thrombotic therapies, patients with acute coronary syndromes (ACS) remain at increased risk of recurrent atherothrombotic events. Dual anti-platelet therapy comprising aspirin and platelet P2Y12 receptor inhibition has become the cornerstone of therapy in ACS. However, thrombin-mediated pathways, which contribute to platelet activation and are responsible for the formation of fibrin clot, remain active following initial plaque rupture. Recently, orally administered drugs which directly target thrombin, factor Xa or thrombin-mediated platelet activation have been developed. Efficacy outcomes in trials of these novel anti-thrombotic agents in ACS have yielded mixed results and their adoption in clinical practice is currently hampered due to a penalty of increased bleeding. To date, the direct Xa inhibitor rivaroxaban and the protease-activated receptor-1 antagonist atopaxar have shown most promise and require further evaluation to determine their role in ACS management.     

In vitro antioxidant activity of two molluscs, Loligo duvauceli Orbigny and Donax cuneatus Linnaeus, by solvent extraction methods

The aim of this study was to assess the in vitro antioxidant activity of solvent extracts prepared from two Indian molluscs viz., Loligo duvauceli Orbigny and Donax cuneatus Linnaeus. For this purpose, several tests were used such as DPPH (2,2-diphenyl-1-picrylhydrazyl), reducing ability and total antioxidant activity. Ethyl acetate extract of Loligo duvauceli showed higher DPPH radical scavenging activity (58%), reducing ability and antioxidant activity (64%) compared to other extracts. All the extracts showed concentration-dependent activity, and increase in concentration increased the antioxidant activities. Therefore, solvent extracts of L. duvauceli and D. cuneatus are rich sources of antioxidants that justify their wide use as natural antioxidants and points out other possible therapeutical uses in the different diseases produced by free radicals.     

Old class but new dimethoxy analogue of benzimidazole: a bacterial topoisomerase I inhibitor

New antimicrobials are needed to combat drug resistance and have often been equated with the identification and exploitation of novel targets. This study focused on the synthesis of new benzimidazole analogues with improved DNA minor groove-binding affinity and having lower cytotoxicity to mammalian cells as well as selective targeting of bacterial DNA over host DNA. 5-(4-Methylpiperazin-1-yl)-2-[2′-(3,4-dimethoxyphenyl)-5′-benzimidazolyl]benzimidazole (DMA) cleared bacterial infections from mammalian cell culture without apparent cytotoxicity to mammalian cells. Moreover, DMA inhibited microbial topoisomerase over mammalian topoisomerase, with a 50% inhibitory concentration (IC₅₀) value for human topoisomerase I of >54 μM compared with an IC₅₀ of <10 μM for Escherichia coli topoisomerase I in vitro.