Extracellular Matrix Remodeling and Modulation of Inflammation and Oxidative Stress by Sulforaphane in Experimental Diabetic Peripheral Neuropathy

Inflammation. 2018 Aug;41(4):1460-1476. doi: 10.1007/s10753-018-0792-9.

Abstract

The peripheral nervous system is one of many organ systems that can be profoundly impacted in diabetes mellitus. Diabetic peripheral neuropathy has a significant negative effect on patients' quality of life as it begins with loss of limbs' sensation and may result in lower limb amputation. This investigation aimed at exploring the effect of sulforaphane on peripheral neuropathy in diabetic rats. Experimental diabetes was induced through single intraperitoneal injections of nicotinamide (50 mg/kg) and streptozotocin (52.5 mg/kg). Rats were divided into five groups. Two groups were treated with saline or sulforaphane (1 mg/kg, p.o.). Three diabetic groups were either untreated or given sulforaphane (1 mg/kg, p.o.) or pregabalin (10 mg/kg, i.p.). Two weeks after drugs' administration, biochemical, behavioral, histopathological, and immunohistochemical investigations were carried out. Treatment with sulforaphane restored animals' body weight, reduced blood glucose, glycated hemoglobin, and increased insulin levels. In parallel, it normalized motor coordination and the latency withdrawal time of tail flick test, increased the latency withdrawal time of cold allodynia test, and ameliorated histopathological changes. Treatment of sulforaphane, likewise, decreased sciatic nerve malondialdehyde, nitric oxide, interleukin-6, and matrix metalloproteinase-2 and -9 contents. Similarly, it reduced sciatic nerve DNA fragmentation and expression of cyclooxygenase-2 and nuclear factor kappa-B p65. Meanwhile, it increased sciatic nerve superoxide dismutase and interleukin-10 contents. These results reveal the neuroprotective effect of sulforaphane against peripheral neuropathy in diabetic rats possibly through modulating oxidative stress, inflammation, and extracellular matrix remodeling. Graphical Abstract Diagram that illustrates the effects of sulforaphane in treating experimental diabetic peripheral neuropathy. In NA-STZ model of diabetes mellitus, sulforaphane, restored animals' body weight, reduced blood glucose, glycated hemoglobin and increased insulin levels. In parallel, it normalized motor coordination and the latency withdrawal time of tail flick test, increased the latency withdrawal time of cold allodynia test and ameliorated histopathological changes. Treatment of sulforaphane, likewise, decreased sciatic nerve malondialdehyde, nitric oxide, interleukin-6, matrix metalloproteinase-2 and -9 contents. Similarly, it reduced sciatic nerve DNA fragmentation and expression of cyclooxygenase-2 and nuclear factor kappa-B p65. Meanwhile, it increased sciatic nerve superoxide dismutase and interleukin-10 contents.

Keywords: diabetic peripheral neuropathy; extracellular matrix remodeling; inflammation; oxidative stress; streptozotocin; sulforaphane.

MeSH terms

  • Animals
  • Anticarcinogenic Agents
  • Blood Glucose / drug effects
  • Body Weight / drug effects
  • Diabetes Mellitus, Experimental / complications
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / pathology
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Inflammation / drug therapy*
  • Isothiocyanates / pharmacology*
  • Oxidative Stress / drug effects*
  • Psychomotor Performance / drug effects
  • Rats
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / metabolism

Substances

  • Anticarcinogenic Agents
  • Blood Glucose
  • Isothiocyanates
  • sulforafan