Evaluation of the therapeutic effects of calcium dobesilate in sciatic nerve crush injury in rats

Injury. 2022 Nov;53(11):3624-3635. doi: 10.1016/j.injury.2022.08.061. Epub 2022 Aug 30.

Abstract

Introduction: Proinflammatory cytokines released from nerve endings and surrounding injured tissue after nerve damage can prolong the inflammation process, delay nerve healing or result in poor quality nerve healing. In this case, due to the loss of function in the muscles innervated by the damaged nerve, the patient may have neurological and functional difficulties which may reduce the patient's quality of life and create an economic burden. Although the attempts of many pharmacological agents to heal crush injury of peripheral nerves have been recorded in literature, a drug that can provide adequate recovery of the crushed nerve and can be applied in daily life has not been defined as yet. This study aimed to assess the effects of calcium dobesilate on sciatic nerve crush injury in a rat model.

Methods: A total of 26 male Wistar albino rats were separated into four groups as follows: CONTROL group (healthy subjects, n=6); SHAM group (crush injury was created, n=6); MP group (after created crush injury, methylprednisolone was administered, n=7); and CAD group (after created crush injury, calcium dobesilate was administered, n=7). A crush injury was created, then the electrophysiological findings and sciatic nerve functional index (SFI) were recorded before euthanasia. After the euthanasia of all the rats, samples of the crushed nerve and gastrocnemius muscle were evaluated histopathologically, immunohistochemically, and biochemically.

Results: Both pharmacological agents were histopathologically effective in axon regeneration and repair. Calcium dobesilate did not preserve total muscle mass but was seen to prevent atrophy microscopically. Immunohistochemistry and biochemistry results showed that calcium dobesilate and methylprednisolone had anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-autophagic activity in the crushed sciatic nerve. Neither calcium dobesilate nor methylprednisolone improved the nerve conductance level. SFI values obtained on day 30 from the CAD group were numerically closer to the values of the healthy animals but not at a statistically significant level.

Conclusion: The study results demonstrated that calcium dobesilate could suppress inflammatory processes and provide histopathological and functional improvements in the injured nerve in rats. Therefore, further clinical studies are recommended to investigate in detail the therapeutic effects of calcium dobesilate on peripheral nerve crush injury.

Keywords: Calcium dobesilate; Crush injury; Methylprednisolone; The sciatic nerve.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / pharmacology
  • Axons / pathology
  • Calcium Dobesilate* / pharmacology
  • Calcium Dobesilate* / therapeutic use
  • Crush Injuries* / drug therapy
  • Cytokines
  • Male
  • Methylprednisolone / pharmacology
  • Methylprednisolone / therapeutic use
  • Nerve Regeneration / physiology
  • Peripheral Nerve Injuries*
  • Quality of Life
  • Rats
  • Rats, Wistar
  • Recovery of Function
  • Sciatic Nerve / injuries
  • Sciatic Neuropathy* / drug therapy
  • Sciatic Neuropathy* / pathology

Substances

  • Calcium Dobesilate
  • Antioxidants
  • Methylprednisolone
  • Anti-Inflammatory Agents
  • Cytokines