Laser-Engineered Retinoid Nanocarriers Mitigate Isotretinoin-Induced Hepatic Injury: A Multilevel Hematological, Physiological, Molecular, and Histopathological Study in Rats

Abstract

Isotretinoin is an effective retinoid that is used as a treatment for severe acne, but its implementation is limited due to systemic adverse events, especially hepatotoxicity, which presents a challenge to clinical use. The current study was organized to examine the hematological, biochemical, molecular, and histopathological effects of isotretinoin on liver function in male rats, emphasizing the modulatory effect of laser-aided treatment. Forty adult male albino rats (8 experimental groups) were administered isotretinoin 20 mg/kg and 40 mg/kg orally at 24, 48, and 72 h time intervals over 30 days. Complete blood count analysis was done for the hematological parameters. Liver function was evaluated as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Molecular markers of liver injury, such as fatty acid–binding protein 1 (FABP1) and kallistatin, were analyzed by ELISA. Liver tissue histopathological evaluation was conducted with hematoxylin and eosin staining. It is demonstrated that significant dose- and time-dependent changes of hematological indices, including leukocyte imbalance and lower erythrocyte parameters and platelet variability, following isotretinoin treatment. The level of ALT, AST, and ALP were markedly elevated, suggesting hepatic insufficiency. Moreover, isotretinoin markedly increased the levels of FABP1 and decreased the levels of kallistatin, indicating hepatocellular injury and functional impairment of protection mechanisms. Histopathological findings indicated hepatocellular degeneration, vascular congestion, inflammatory infiltration, and sinusoidal dilatation that provided strong evidence of these biochemical and molecular alterations. Of interest, laser-associated treatment led to a marked decrease in isotretinoin toxicity (partial normalization of hematology), (reduction in liver enzyme activity, and) (modulation of FABP1 and kallistatin levels) and (enhancement of hepatic tissue architecture). These findings indicate that laser-based modulation plays a hepatoprotective role by promoting cellular integrity and liver repair processes. This can be an important strategy in treating isotretinoin-induced hepatic injury through integration of physiological, molecular, and histopathological factors and may provide evidence to enhance the safety and effectiveness of retinoid treatment via laser-assisted isotretinoin treatment.