A Quantitative Approach to Evaluate Rhus Coriaria Nanophytosomes in Ketamine-Induced Liver Injury

Abstract

Ketamine, a commonly used anesthetic, is known to induce hepatotoxicity mainly through elevation of serum liver enzymes. Rhus coriaria (sumac) possesses notable antioxidant properties; however, its therapeutic potential is hindered by poor bioavailability. This study aimed to evaluate the protective effects of sumac and its nanophytosome formulation against ketamine-induced liver injury in male mice. Twenty-five mice were randomly divided into five groups: control, nanophytosome control, ketamine <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$(20 \text{mg} / \text{kg})$</tex>, sumac-treated, and sumac-nanophytosome-treated. After 15 days, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. The synthesized sumac nanophytosomes were characterized for particle size and encapsulation efficiency. Ketamine administration significantly elevated ALT <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$(150 \pm 12 \mathrm{U} / \mathrm{L})$</tex> and AST <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$(180 \pm 15 \mathrm{U} / \mathrm{L})$</tex> compared with the control group (ALT <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$45 \pm 6$</tex>, AST <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$52 \pm 7$</tex>; <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$\mathrm{p}&lt;0.001)$</tex>. Treatment with sumac nanophytosomes markedly reduced these enzyme levels (ALT <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$68 \pm 9, p=0.002, \eta^{2}=0.62$</tex>; AST <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$92 \pm$</tex> 11, <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$\mathbf{p}&lt;0.001, \boldsymbol{\eta}^{2}=0.71)$</tex>, whereas the crude sumac extract showed a weaker effect (ALT <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$102 \pm 13$</tex>, AST <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$138 \pm 12)$</tex>. These findings indicate that sumac nanophytosomes exert substantial hepatoprotective effects against ketamine-induced liver injury, likely due to improved bioavailability and antioxidant capacity. This study highlights a promising nanotechnology-based strategy for mitigating drug-induced hepatotoxicity and provides the first direct comparison between crude and nanophytosome forms of sumac in this context.