Abstract
Background: Sodium valproate (SVP) is a widely prescribed treatment for epilepsy and other neurological diseases. However, liver injury is a harmful side effect related to its usage. Oxidative stress, inflammation, and fibrosis seem to play a major role in SVP-induced hepatotoxicity. Aim of the work: This work aimed, for the first time, to study the possible protective mechanisms of ginger (GN) in modulating the hepatotoxic effects of SVP in albino rats. Material and methods: A total of 24 Sprague-Dawley adult male rats (180g - 220g) were divided into equal four groups: Group1 (control): received normal saline by gavage. Group2 (GN): received ginger (200mg/kg/day). Group3 (SVP): received SVP (300mg/kg/day). Group4 (GN+SVP): received combined ginger (200mg/kg/day) and SVP (300mg/kg/day).All medications were administrated dailyfor 14 days by gavage. At the assigned time the animals were sacrificed, the blood and tissue samples were collected and processed for biochemical, histological, and immunohistochemical studies. Result: SVP treatment induced a significant increase in alanine transaminase, aspartate transaminase, and Malondialdehyde (ALT, AST, and MDA respectively), together with a significant reduction in the antioxidant enzyme Glutathione (GHS) indicated hepatic oxidative stress damage. Histological examination revealed loss of the normal hepatic architecture, extensive fibrosis identified by Masson's trichrome staining. Moreover, the SVP group showed a significant increase in tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) Immunohistochemical expression. Co-treatment with GN significantly reversed the previous changes in the GN+SVP group. Conclusion: In conclusion, ginger has hepatoprotective activity due to its anti-oxidant, anti-inflammation, and anti-fibrotic potentials.
Highlights
Sodium valproate (SVP) is frequently prescribed as an antiepileptic medication to treat epilepsy, convulsions, and migraines (Tolou-Ghamari Z and Palizban, 2015).Marwa Abd El-kader and Omnia S
II- Histological Results: A) Haematoxylin and Eosin: The hematoxylin and eosin (H&E) sections of the control and GN groups revealed nearly the same histological structures. Both groups showed that each hepatic lobule was formed of a central vein encircled by radiating cords of hepatocytes disjointed by blood sinusoids
The portal area was formed of a portal vein with a thin wall and large lumen and a bile duct that was lined by single cuboidal cells containing dark, rounded nuclei (Fig. 2A, 1B)
Summary
Sodium valproate (SVP) is frequently prescribed as an antiepileptic medication to treat epilepsy, convulsions, and migraines (Tolou-Ghamari Z and Palizban, 2015).Marwa Abd El-kader and Omnia S. Sodium valproate (SVP) is frequently prescribed as an antiepileptic medication to treat epilepsy, convulsions, and migraines (Tolou-Ghamari Z and Palizban, 2015). The mechanism of liver injury is not completely identified; SVP-induced liver toxicity includes several mechanisms including oxidative stress, inflammation, and fibrosis (Abdelkader et al, 2020; Salimi et al, 2020). Oxidative stressrelated excessive reactive oxygen species (ROS) production and unbalanced antioxidant ability play an essential role in the SVP-related toxicity. SVP-induced inflammatory and immune reactions cause the release of inflammatory cytokines regulated by TNF-α. Several previous studies illustrated a significant increase in the TNF-α expression after SVP treatment (Nazmy et al, 2017; Oztopuz et al, 2020). Sodium valproate (SVP) is a widely prescribed Aim of the work: This work aimed, for the first time, to study the possible protective mechanisms of ginger (GN) in modulating the TGF-β, Ginger hepatotoxic effects of SVP in albino rats
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More From: Egyptian Academic Journal of Biological Sciences, D. Histology & Histochemistry
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