Histological investigation and three dimensional modeling of the boric acid effects on vascularization and regeneration in acetaminophen-induced liver injury

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Thesis Type: Doctorate

Institution Of The Thesis: Gazi University, Sağlık Bilimleri Enstitüsü, Turkey

Approval Date: 2024

Thesis Language: Turkish

Student: Müşerref Şeyma CEYHAN

Principal Supervisor (For Co-Supervisor Theses): Suna Ömeroğlu

Co-Supervisor: Zeynep Yığman

Abstract:

Acetaminophen is a commonly-used drug due to its analgesic and antipyretic effects. Overdosing of acetaminophen may lead to liver damage, which may result in organ failure. Türkiye is one of the geographical regions that has the most important boron reserves in the world. The latest studies about boric acid, a compound of boron considered as essential element, revealed antiinflammatory and antioxidant effects. In this study, we aimed to investigate the effects of boric acid on vascularization and regeneration in acetaminophen induced liver injury. 35 adult, male Sprague Dawley rats were randomly divided into 5 groups, each containing 7 rats. Groups were designed as control, acetaminophen, boric acid treatment 1 hour after acetaminophen administration, boric acid treatment 8 hours after acetaminophen administration and boric acid groups. After 24 hours of acetaminophen application, animals were sacrified. ALT, AST, GGT, total bilirubin, ALP and glucose levels were evaluated biochemically and hepatic injury, glycogen depletion, VEGF-A, AFP and PCNA expressions were evaluated histochemically and immunohistochemically using the liver and blood samples collected at the end of experiments. Three-dimensional modeling was constituted to better demonstrate the histopathology of liver injury. Boric acid treatment in acetaminophen-induced liver injury resulted in a decrease in hepatic injury including centrilobular necrosis, vascular congestion, inflammatory cell infiltration and hemorrhage, glycogen depletion, ALT, GGT and total billirubin levels on the other hand an increase VEGF-A expression and PCNA positive cell percentage occured. Results showed that boric acid treatment at different time points of acetaminophen induced liver injury reduced the severity of damage.

Key Words : Acetaminophen, Boric acid, Liver injury, Regeneration