Investigation of Changes in the Effect of Esculetin in Aluminum-induced Experimental Rat Toxicity Model
Project no. 28441 · Status: Kapanmış (Yayın bekleniyor) · 2023
Summary
<p><strong>Aim:</strong> The aim of this study was to investigate the possible protective effects of different doses of esculetin on the changes developing in the brain in aluminium chloride-induced rat toxicity model by histological and biochemical methods.</p><p><strong>Method: </strong>64 male Wistar albino rats weighing 250-300 grams, 10-12 weeks old were divided into Control, AlCl3, ESC50, ESC100, ESC200, AlCl3+ESC50, AlCl3+ESC100 and AlCl3+ESC200 groups as n:8 and the experimental protocol was applied for 28 days. Open field test was performed one day before sacrification. The weights of the subjects were recorded throughout the experiment and brain weights were measured during sacrification. After sacrification, brain tissues were prepared for histological and biochemical analyses. In histological analyses, Anti-GFAP, Anti-NSE and Anti-Nrf2 immunohistochemical stainings were performed in addition to Hematoxylin-Eosin and Cresyl-Echt Violet histochemical stainings. Biochemical analysis included MDA and catalase measurements. The data obtained were statistically evaluated.</p><p><strong>Results: </strong>In the open field test, it was found that the time spent in the center area decreased and the number of defecations increased in the AlCl3 group, and these changes were similar to the control in the AlCl3+ESC200 group. When the weight changes of the subjects were examined on days 1-14 and 14-28, a significant weight loss was observed in the groups administered AlCl3 on days 1-14 and in the AlCl3 group on days 14-28, while an increase in weight was observed especially in the AlCl3+ESC100 and AlCl3+ESC200 groups in addition to the groups receiving only esculeti. In brain mass index analysis, ESC100 and AlCl3+ESC50 groups had higher mean weights compared to control and AlCl3 groups. Histochemical staining in the cerebral cortex and CA1 and CA3 regions of the hippocampus showed gliosis, pyknotic neurons, neuropil and pyramidal cells with neurofibrillary tangle-like axonal degeneration accompanied by vacuolization in the cytoplasm in the AlCl3 group, while these changes decreased and the number of healthy neurons and neuropil increased in parallel with the dose increase with esculetin administration. Anti-GFAP expression was significantly increased in all three regions in the AlCl3 group and decreased to similar levels with the control group, especially in the AlCl3+ESC200 group. Similarly, anti-NSE expression, which increased in the AlCl3 group, decreased significantly in the AlCl3+ESC100 and AlCl3+ESC200 groups and decreased to a level close to the control group. It is noteworthy that anti-Nrf2 expression increased in ESC50, ESC100 and ESC200 groups compared to the Control group, while a significant decrease was detected in the AlCl3 group. Anti-Nrf2 expression increased in the groups receiving esculetin, especially in the AlCl3+ESC200 group, compared to the AlCl3 group. Biochemical analysis showed that MDA increased in the AlCl3 group and no significant change was found in the statistical analysis of catalase results.</p><p><strong>Conclusion: </strong>In our study, it was shown by histochemical, immunohistochemical, biochemical methods and behavioral experimental analyses that AlCl3 administration causes neurodegenerative and neurotoxic changes. Esculetin was found to be effective in reducing these changes and 200 mg/kg esculetin dose was found to be the most effective dose. For the clinical use of esculetin, the cellular mechanisms that produce these neuroprotective effects should be investigated with further experimental and clinical studies.</p><p><strong>Keywords; </strong>Aluminium; Esculetin; Cell death; Neurotoxicity</p>