Neuroprotective effects of lovastatin against traumatic spinal cord injury in rats

J Chem Neuroanat. 2022 Nov:125:102148. doi: 10.1016/j.jchemneu.2022.102148. Epub 2022 Aug 27.

Abstract

Background: Lovastatin, as a drug of statins subgroup, has been conceptualized to have anti-inflammatory, antioxidant, and anti-apoptotic properties. Accordingly, the present study aimed to investigate the neuroprotective ramification of lovastatin on spinal cord injury (SCI).

Material and methods: Seventy-five female adult Wistar rats were divided into five groups (n = 15). In addition to non-treated (Control group) and laminectomy alone (Sham group), SCI animals were randomly assigned to non-treated spinal cord injury (SCI group), treated with 2 mg/kg of lovastatin (Lova 2 group), and treated with 5 mg/kg of lovastatin (Lova 5 group). At the end of the study, to evaluate the treatments, MDA, CAT, SOD, and GSH factors were evaluated biochemically, apoptosis and gliosis were assessed by immunohistochemical while measuring caspase-3 and GFAP antibodies, and inflammation was estimated by examining the expression of IL-10, TNF-α, and IL-1β genes. The stereological method was used to appraise the total volume of the spinal cord at the site of injury, the volume of the central cavity created, and the density of neurons and glial cells in the traumatic area. In addition, Basso-Beattie-Bresnehan (BBB) and narrow beam test (NBT) were utilized to rate neurological functions.

Results: Our results exposed the fact that biochemical factors (except MDA), stereological parameters, and neurological functions were significantly ameliorated in both lovastatin-treated groups, especially in Lova 5 ones, compared to the SCI group. The expression of the IL-10 gene was significantly upregulated in both lovastatin-treated groups compared to the SCI group and was considerably heighten in Lova 5 group. Expression of TNF-α and IL-1β, as well as the rate of apoptosis and GFAP positive cells significantly decreased in both lovastatin treated groups compared to the SCI group, and it was more pronounced in the Lova 5 ones.

Conclusion: Overall, using lovastatin, especially at a dose of 5 mg/kg, has a dramatic neuroprotective impact on SCI treatment.

Keywords: Inflammation; Lovastatin; Neuroprotective; Oxidative stress; Spinal cord injury.

MeSH terms

  • Animals
  • Apoptosis
  • Disease Models, Animal
  • Female
  • Interleukin-10 / metabolism
  • Lovastatin / metabolism
  • Lovastatin / pharmacology
  • Lovastatin / therapeutic use
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Rats
  • Rats, Wistar
  • Spinal Cord / metabolism
  • Spinal Cord Injuries* / drug therapy
  • Spinal Cord Injuries* / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-10
  • Lovastatin
  • Neuroprotective Agents
  • Tumor Necrosis Factor-alpha