The Correlation of Histopathological Findings with Ultrastructural Changes in Hepatocytes after Yangonin “Ya”-Intoxicated Rats Alone and In Combination with EtOH: Sub-Acute & Sub-Chronic Study

Abstract

Yangonin “Ya” has been used for centuries as a herbal supplement, for its mood-altering properties. It has been used as a recreation agent, for relaxation, as well as for pain relief. However, hepatotoxicity is a widespread problem associated with medicines in general. Most herbal supplements are metabolized by the liver, and thus the liver represents the target organ. At present, Yangonin toxicity appears to be “idiosyncratic”. Therefore, a study was designed in order to investigate the organelle-based changes in hepatocytes, after treatment with Yangonin alone and in combination with EtOH. Thirty rats were divided into five groups comprising of six animals each. The groups comprised of the control groups {(NCx) & (PCx)}, Yangonin (Ya) group, ethanol (EtOH) group, and the combination of (Ya) and ethanol (EtOH+Ya) group. The experiment was conducted over a period of 14 weeks, as a sub-chronic study. At the end of the 14 th week, mitochondria, peroxisome, rough and smooth endoplasmic reticulum, and nuclei of hepatocytes, were evaluated using a scoring system. The results were compared with histopathological findings, as well. Treatment with Ya significantly induced hepatotoxic scores as compared to the control groups. Organelle injury scores increased significantly with Ya treatment, while rats that received “EtOH+Ya” showed the severest lesions of liver scores such as, severe hepatocellular degeneration, necrosis, and hypertrophy. Ultrastructural and histopathological scores in both groups were in very strong correlation (r = 0.928 for EtOH, r = 0.921 for Ya alone and r = 0.903 for Ya plus EtOH group). In conclusion, ethanol enhanced the sedative and hypnotic activity of Ya, and markedly increased toxicity. Findings based on TEM examination of organelles, supported the histological results as well as tissue lesions/injuries in hepatocytes, a result of hepatotoxin-induced hepatopathy.