Effects of immune cell-targeted treatments result from the suppression of neuronal oxidative stress and inflammation in experimental diabetic rats.

Abstract

In this study, we hypothesized that reduction of immune cell activation as well as their oxidant or inflammatory mediators with minocycline (MCN), liposome-encapsulated clodronate (LEC), or anti-Ly6G treatments can be neuroprotective approaches in diabetic neuropathy. MCN (40mg/kg) for reduction of microglial activation, LEC (25mg/kg) for of macrophage inhibition, or anti-Ly6G (150μg/kg) for neutrophil suppression injected to streptozotocin (STZ)-induced diabetic rats twice, 3days, and 1week (half dose) after STZ. Animal mass and blood glucose levels were measured; thermal and mechanical sensitivities were tested for in pain sensations. The levels of chemokine C-X-C motif ligand 1 (CXCL1), CXCL8, and C-C motif ligand 2 (CCL2), CCL3, and total oxidant status (TOS) and total antioxidant status (TAS) were measured in the spinal cord and sciatic nerve tissues of rats. LEC significantly reduced the glucose level of diabetic rats compared with drug control. However, MCN or anti-LY6G did not change the glucose level. While diabetic rats showed a marked decrease in both thermal and mechanical sensations, all treatments alleviated these abnormal sensations. The levels of chemokines and oxidative stress parameters increased in diabetic rats. All drug treatments significantly decreased the CCL2, CXCL1, and CXCL8 levels of spinal cord tissues and ameliorated the neuronal oxidative stress compared with control treatments. Present findings suggest that the neuroprotective actions of MCN, LEC, or anti-Ly6G treatments may be due to the modulation of neuronal oxidative stress and/or inflammatory mediators of immune cells in diabetic rats with neuropathy.