Protective Effect of Isovaleramide on Brain Damage in Rats with Acute Ethylene Glycol Poisoning
Objective To explore the protective effect of isovaleramide(ISO)in ethylene glycol(EG)-induced acute toxic brain injury rat model and its possible mechanism.Methods A total of 55 SPF SD male rats were divided into 4groups by random number table method,and 15 rats in the EG poisoning group(EG group):80%EG solution was injected into the stomach at the rate of 12ml/kg;10 rats in the blank control group(NC group):they were given 12ml/kg of normal saline;15 rats each in the low-dose ISO intervention group and the high-dose ISO intervention group(EG + ISO-L and EG + ISO-H group):they were given 80%EG solution at the rate of 12ml/kg,and then 10mg/ml and 20mg/ml ISO solution were injected through the tail vein at the rate of 1ml/kg,respectively.Blood was collected from the abdominal aorta 24hours after the modeling and sacrificed,the brain and other related tissues were collected.The level of S100 calc-binding protein β(S100-β),water content of the brain tissue and behavioral score of the rats were detected by en-zyme-linked immunosorbent assay(ELISA)to determine the degree of cerebral edema and behavioral changes.HE staining and Pizzola-to staining were used to observe the pathological changes and calcium oxalate crystal formation of the brain tissue.Western blot was used to detect the expression of related apoptotic proteins.Micromethods was used to detect the alcohol dehydrogenase(ADH)activity in liver of the rats.Visible light spectrophotometry was used to detect the level of oxalic acid in the blood of each group.Results The brain his-topathological changes of EG group were obvious,calcium oxalate crystals formed in cerebral vessels,brain water content was increased,behavioral scores was decreased,serum S100-β protein content and apoptotic protein expression were increased(P<0.05).ADH ac-tivity and oxalic acid production in EG + ISO-L and EG + ISO-H groups were significantly decreased compared with EG group(P<0.05),brain histopathological changes were alleviated,calcium oxalate crystals in cerebral vessels were less,behavioral scores were in-creased;brain water content,serum protein content and apoptotic protein expression were decreased compared with EG group(P<0.05).Conclusion ISO has protective effect on brain injury caused by acute EG poisoning in rats,which may be related to inhibiting the activity of ADH and reducing oxalic acid produced by EG metabolism.
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