Vitamin E and 5-amino salicylic acid ameliorates acrylamide-induced peripheral neuropathy by inhibiting caspase-3 and inducible nitric oxide synthase immunoexpression

J Chem Neuroanat. 2021 Apr:113:101935. doi: 10.1016/j.jchemneu.2021.101935. Epub 2021 Feb 12.

Abstract

Acrylamide is a fundamental cause of accidental toxicity in humans. This study aimed to investigate the neuroprotective effect of vitamin E (Vit. E), 5-amino salicylic acid (5-ASA), and their combination against acrylamide-induced sciatic nerve toxicity. For this purpose, 25 male Wister rats were divided into 5 groups: control, acrylamide, acrylamide + Vit. E, acrylamide + 5-ASA, and acrylamide + Vit. E + 5-ASA. Food intake and body weight were assessed after 7 days. Furthermore, the gait score was also evaluated for each rat. The sciatic nerve was dissected, fixed, and processed for routine light and electron microscopic examination. Haematoxylin and eosin, osmium tetroxide for myelin sheath, and toluidine blue for semithin section were used. In addition, immunohistochemistry for caspase-3 and inducible nitric oxide synthase (iNOS) were performed. The results showed reduced food intake and body weight in acrylamide rats. Abnormal gait score was also recorded in acrylamide rats with significant improvement in Vit. E, and Vit. E + 5-ASA groups. Histologically, Vit. E and 5-ASA provided potential protection against decreased sciatic nerve axon density, disrupted myelination, and the alteration in the immunohistochemistry induced by acrylamide. Vit. E and its combination with 5-ASA provided more evident protection compared to 5-ASA alone. 5-ASA significantly decreased apoptotic cell death (caspase-3 immunoexpression) while Vit. E failed. Both Vit. E and 5-ASA significantly decreased iNOS immunoexpression in the sciatic nerve, where 5-ASA was superior to Vit. E. These findings concluded that both Vit. E and 5-ASA protect against acrylamide-induced peripheral neuropathy through downregulation of both caspase-3 and iNOS immunoexpression.

Keywords: 5-Amino salicylic acid; Acrylamide; Caspase-3; Histology; Inducible nitric oxide synthase; Sciatic nerve; Vitamin E.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamide
  • Animals
  • Caspase 3 / metabolism*
  • Immunohistochemistry
  • Male
  • Mesalamine / pharmacology
  • Mesalamine / therapeutic use*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Nitric Oxide Synthase Type II / metabolism*
  • Peripheral Nervous System Diseases / chemically induced
  • Peripheral Nervous System Diseases / drug therapy*
  • Peripheral Nervous System Diseases / metabolism
  • Rats
  • Rats, Wistar
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / metabolism
  • Vitamin E / pharmacology
  • Vitamin E / therapeutic use*

Substances

  • Neuroprotective Agents
  • Vitamin E
  • Acrylamide
  • Mesalamine
  • Nitric Oxide Synthase Type II
  • Caspase 3