Amelioration of the Protein Expression of Cox2, NFκB, and STAT-3 by Some Antioxidants in the Liver of Sodium Fluoride–Intoxicated Rats

Abstract

The present study aimed to explore the efficiency of N-acetyl cysteine (NACC) or thymoquinone (TMQ) alone or in combination in the downregulation of inflammatory molecule expression and decreasing hepatic injury in response to sodium fluoride (SF). Sodium fluoride upregulated serum alanine and aspartate transferases activities, tumor necrosis factor α and hepatic malondialdehyde and nitric oxide levels, and the expression of cyclooxygenase 2, nuclear factor κB cell, and signal transducer and activator of transcription 3. In contrast, hepatic glutathione level, superoxide dismutase activity, and nuclear factor erythroid 2-related factor 2 expression were decreased. However, the concurrent treatment with antioxidants, alone or in combination, modulated the levels of these parameters. Histopathological examination revealed that SF treatment resulted in focal areas of massive hepatic degeneration and many degenerated hepatocytes, whereas the treatment with TMQ or NACC exhibited moderate improvement in cellular degeneration of the liver with many abnormal cells. Rats receiving a combination of TMQ and NACC showed marked improvement in cellular degeneration of liver with apparently normal hepatic architecture with very few degenerated hepatocytes. The results also revealed that the combination of TMQ and NACC is the most effective regimen in ameliorating SF toxicity, suggesting their efficacy against the toxicity of fluoride compounds. Their activities might be mediated via multiple molecular pathways.

Research on the Potential Mechanism of Gypenosides on Treating Thyroid-Associated Ophthalmopathy Based on Network Pharmacology

“…Research suggests that inhibiting the expression of STAT1 signaling pathway can inhibit the production of IP-10/CXCL 10 induced by IFN-γ in orbital fibroblasts of patients with TAO, thereby alleviating orbital inflammation [29]. The STAT3 signaling pathway might play an anti-inflammatory, antioxidant, and immunomodulatory role in chronic respiratory diseases, breast cancer, and liver inflammation [30–32]. Inflammation and oxidative stress damage to orbital tissue is the main pathogenesis of TAO [33,34].…”

Molecular Mechanism of Changes in Gene Expression of Cytosolic Cu/Zn SOD, Lipid Peroxidation and Hepatic Function Impairments during Experimental Fluorosis

“…A significant increase in the activities of aminotransferases in present study might be due to oxidative stress generated by sodium fluoride which could alter the membrane permeability of hepatocytes in rats treated with 300 and 600 mg/L NaF. Fluoride toxicity induced oxidative damage leads to liver dysfunction and deformities in the levels of serum biomarker transaminases [42]. A marked increase in the activity of ALT was attributed to a change in the permeability of the hepatic cell membrane [43].…”

Sophocarpine attenuates septic liver injury through suppression of the NLRP3 inflammasome via autophagy‑mediated degradation

“…Previous studies have demonstrated that hepatocyte death through mechanisms including apoptosis, necrosis and autophagy, serves a crucial role in septic liver injury (3)(4)(5). The death of vast numbers of hepatocytes leads to elevated levels of AST and ALT and subsequent liver failure (7).…”

“…During sepsis, inflammatory cytokines released from immune cells bind to receptors on hepatocytes and induce the activation of downstream signaling, resulting in the apoptosis or necrosis of hepatocytes (4)(5)(6). Previous studies identified inflammasome activation in hepatocytes as a major cause of hepatocyte cell death and of septic liver injury and failure (7)(8)(9)(10).…”