Chronic Treatment With Hydrogen Sulfide Donor GYY4137 Mitigates Microglial and Astrocyte Activation in the Spinal Cord of Streptozotocin-Induced Diabetic Rats

Autor: Alyaa Mousa, Abdulaziz Shayea, Mohammed Shaban Nadar, Waleed M. Renno, Mariam H. M. Yousif, Bedoor Qabazard
Rok vydání: 2020
Předmět:
Male
medicine.medical_specialty
Diabetic neuropathy
Morpholines
Diabetes Mellitus
Experimental
Pathology and Forensic Medicine
Proinflammatory cytokine
Rats
Sprague-Dawley
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Diabetic Neuropathies
Internal medicine
Diabetes mellitus
medicine
Animals
030304 developmental biology
0303 health sciences
business.industry
Organothiophosphorus Compounds
General Medicine
medicine.disease
Streptozotocin
Rats
Neuroprotective Agents
Treatment Outcome
medicine.anatomical_structure
Peripheral neuropathy
Allodynia
Endocrinology
Spinal Cord
Neurology
Hyperalgesia
Astrocytes
Neuropathic pain
Cytokines
Microglia
Neurology (clinical)
Inflammation Mediators
medicine.symptom
business
030217 neurology & neurosurgery
Astrocyte
medicine.drug
Zdroj: Journal of Neuropathology & Experimental Neurology. 79:1320-1343
ISSN: 1554-6578
0022-3069
DOI: 10.1093/jnen/nlaa127
Popis: Long-term diabetic patients suffer immensely from diabetic neuropathy. This study was designed to investigate the effects of hydrogen sulfide (H2S) on peripheral neuropathy, activation of microglia, astrocytes, and the cascade secretion of proinflammatory cytokines in the streptozotocin (STZ)-induced peripheral diabetic neuropathy rat model. STZ-induced diabetic rats were treated with the water-soluble, slow-releasing H2S donor GYY4137 (50 mg/kg; i.p.) daily for 4 weeks. Antiallodynic/antihyperalgesic activities were evaluated using different tests and histopathological changes and the expression of proinflammatory cytokines in the spinal cord were examined. GYY4137 treatment produced neuroprotective effects in the spinal cord of diabetic animals and modulated their sensory deficits. The treatment decreased allodynia (p < 0.05) and mechanical hyperalgesia (p < 0.01) and restored thermal hyperalgesia (p < 0.001) compared with diabetic rats. The treatment decreased the microglial response and increased astrocyte counts in spinal cord gray and white matter compared with untreated diabetic rats. Proinflammatory cytokines were reduced in the treated group compared with diabetic rats. These results suggest that H2S has a potentially ameliorative effect on the neuropathic pain through the control of astrocyte activation and microglia-mediated inflammation, which may be considered as a possible treatment of peripheral nerve hypersensitivity in diabetic patients.
Databáze: OpenAIRE
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