Kumar Vinod, Tiwari Neeraj, Gedda Mallikarjuna Rao, Haque Rizwanul, Singh Rakesh K
Banaras Hindu University Institute of Science, Department of Biochemistry, Molecular Immunology Laboratory, Varanasi, India; Rajendra Memorial Research Institute of Medical Science, Department of Molecular Biology, Patna, India.
Banaras Hindu University Institute of Science, Department of Biochemistry, Molecular Immunology Laboratory, Varanasi, India.
Braz J Infect Dis. 2017 Sep-Oct;21(5):545-549. doi: 10.1016/j.bjid.2017.04.007. Epub 2017 Jun 9.
The present study was aimed to identify the underlying mechanisms of improper renal function in Leishmania donovani infection that causes VL. Mice (BALB/c) were infected with L. donovani and different parameters for proteinuria were assessed. The levels of superoxide anion (O), hydrogen peroxide (HO), lipid peroxidation (MDA), inflammatory cytokines, and toll-like receptor (TLR) 2 and 4 expression were found significantly elevated at 60th day in these animals and declined at 90th day post infection. However, TGF-β and caspase 3 activities were higher at 90th day in comparison to 60th day post infection. These findings suggested that exacerbated inflammatory conditions correlate with abnormal renal functions in L. donovani infection, which is further augmented by activated TLRs expressions by circulating leishmanial antigens. Further, the increased levels of TGF-β and caspase 3 at 90th day suggested TGF-β mediated apoptotic cell death of renal and other cells during later stages of disease that may eventually result in release of host and parasitic factors in urine during visceral leishmaniasis.
本研究旨在确定导致内脏利什曼病的杜氏利什曼原虫感染中肾功能异常的潜在机制。用杜氏利什曼原虫感染小鼠(BALB/c),并评估蛋白尿的不同参数。在这些动物感染后的第60天,超氧阴离子(O)、过氧化氢(HO)、脂质过氧化(MDA)、炎性细胞因子以及Toll样受体(TLR)2和4的表达水平显著升高,而在感染后第90天下降。然而,与感染后第60天相比,TGF-β和半胱天冬酶3的活性在第90天更高。这些发现表明,在杜氏利什曼原虫感染中,炎症加剧与肾功能异常相关,循环中的利什曼原虫抗原激活TLR表达会进一步加剧这种情况。此外,第90天TGF-β和半胱天冬酶3水平升高表明,在疾病后期,TGF-β介导肾细胞和其他细胞的凋亡性细胞死亡,这最终可能导致内脏利什曼病期间尿液中宿主和寄生因子的释放。