Comparative Neuroprotective Effects of Dexamethasone and Minocycline during Hepatic Encephalopathy

Abstract

Objective. Encephalopathy and brain edema are serious complications of acute liver injury and may lead to rapid death of patients. The present study was designed to investigate the role of the inflammatory mediators and oxidative stress in the cytotoxic brain oedema and the neuroprotective effects of both minocycline and dexamethasone. Methods. 48 male albino rats were divided into 4 groups: control group, acute liver injury (ALI) group, minocycline pretreated ALI group, and dexamethasone pretreated ALI group. 24 hours after acute liver injury serum ammonia, liver enzymes, brain levels of heme oxygenase-1 gene, iNOS gene expression, nitrite/nitrate, and cytokines were measured. In addition, the grades of encephalopathy and brain water content were assessed. Results. ALI was associated with significant increases in all measured inflammatory mediators, oxidative stress, iNOS gene expression, and nitrite/nitrate. Both minocycline and dexamethasone significantly modulated the inflammatory changes and the oxidative/nitrosative stress associated with ALI. However, only minocycline but not dexamethasone significantly reduced the cytotoxic brain oedema. Conclusion. Both minocycline and dexamethasone could modulate inflammatory and oxidative changes observed in brain after ALI and could be novel preventative therapy for hepatic encephalopathy episodes.

Ameliorative effect of oregano (Origanum vulgare) versus silymarin in experimentally induced hepatic encephalopathy

“…Hyperammonemia is caused by the reduced hepatic synthesis of urea and glutamate by which the normal liver removes ammonia from the portal blood 44 , 78 . In liver failure, hyperammonemia affects the mitochondrial function resulting in reduction of ATP synthesis and enhances free radical generation 73 , 75 , 79 . Blood ammonia crosses the blood brain barrier and enters in brain astrocytes.…”

Potential targeted therapies for the inflammatory pathogenesis of hepatic encephalopathy

“…Jiang et al have demonstrated that minocycline inhibited microglial activation and attenuated the up-regulation of TNF-␣, IL-1␤ and IL-6 expression in the brains of ALF rats, thereby preventing cerebral oedema and improving the rats' neurological status [10]. Moreover, pre-treatment with minocycline was associated with significant decreases in the levels of TNF-␣, IL-1␤, IL-6 and cerebral water in ALF rats, and these associations suggest that minocycline is effective in inhibiting the production of pro-inflammatory cytokines and reducing cerebral oedema [42]. These results provide preliminary evidence that minocycline might have therapeutic potential in patients with HE due to ALF.…”

Oxidative stress and COVID-19-associated neuronal dysfunction: mechanisms and therapeutic implications

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