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      Mechanistic insight of diabetic nephropathy and its pharmacotherapeutic targets: An update.

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          Abstract

          Diabetic nephropathy (DN), a chronic complication of diabetes, is charecterized by glomerular hypertrophy, proteinuria, decreased glomerular filtration, and renal fibrosis resulting in the loss of renal function. Although the exact cause of DN remains unclear, several mechanisms have been postulated, such as hyperglycemia-induced renal hyper filtration and renal injury, AGEs-induced increased oxidative stress, activated PKC-induced increased production of cytokines, chemokines, and different inflammatory and apoptotic signals. Among various factors, oxidative stress has been suggested to play a major role underlying the onset and propagation of DN. It triggers several signaling pathways involved in DN, like AGEs, PKC cascade, JAK/STAT signaling, MAPK, mTOR, and SMAD. Oxidative stress-induced activation of both inflammatory and apoptotic signals are two major problems in the pathogenesis of DN. The FDA approved pharmacotherapeutic agents affecting against polyol pathway principally include anti-oxidants, like α-lipoic acid, vitamin E, and vitamin C. Kremezin and benfotiamine are the FDA approved AGEs inhibitors, another therapeutic target against DN. Ruboxistaurin, telmizartan, rapamycin, fenofibrate, aliskiren, and manidipine are some FDA approved pharmacotherapeutics effective against DN via diverse mechanisms. Beside this, some therapeutic agents are still waiting for FDA approval and few drugs without FDA approval are also prescribed in some countries for the management of DN. Despite the medications available in the market to treat DN, the involvement of multiple mechanisms makes it difficult to choose an optimum therapeutic agent. Therefore, much research is required to find out new therapeutic agent/strategies for an adequate pharmacotherapy of DN.

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          Author and article information

          Journal
          Eur. J. Pharmacol.
          European journal of pharmacology
          Elsevier BV
          1879-0712
          0014-2999
          Nov 15 2016
          : 791
          Affiliations
          [1 ] Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700032, India.
          [2 ] Biological Science and Technology Division, CSIR-NEIST, Jorhat, Assam 785006, India.
          [3 ] Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700032, India. Electronic address: s.dewanjee@yahoo.com.
          [4 ] Biological Science and Technology Division, CSIR-NEIST, Jorhat, Assam 785006, India. Electronic address: pmanna2012@gmail.com.
          Article
          S0014-2999(16)30541-6
          10.1016/j.ejphar.2016.08.022
          27568833

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