Comparative effects of Helmar-1 and Helmar-2 polyphenol extracts on mitochondrial bioenergetics, antioxidant defense, and lipid peroxidation in CCl₄-induced toxic hepatitis in rats

Abstract

ABSTRACT Introduction: Toxic hepatitis is characterized by enhanced oxidative stress and disruption of antioxidant defense mechanisms in the liver mitochondria. In this study, we investigated the effects of polyphenolic extracts (Helmar-1 and Helmar-2) obtained from Helichrysum maracandicum on mitochondrial antioxidant systems in rats with experimentally induced toxic hepatitis. Methods: Experimental toxic hepatitis was established in rats through intraperitoneal administration of carbon tetrachloride (CCl₄) diluted in olive oil (50%, 1 mL/kg), administered twice weekly over a two-week period. Liver injury was verified by elevated plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The animals were subsequently treated with Helmar-1 and Helmar-2 extracts at a dose of 20 mg/kg per day for 10 consecutive days. The activities of key antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), malondialdehyde (MDA) content, and mitochondrial respiration and oxidative phosphorylation parameters (V₂, V₃, V₄, RCR, and ADP/O ratio) were assessed in liver mitochondria. Results: Treatment with both Helmar-1 and Helmar-2 extracts resulted in a significant enhancement of antioxidant enzyme activities, a marked reduction in MDA levels, and substantial improvement in mitochondrial respiration and oxidative phosphorylation parameters compared to untreated toxic hepatitis groups. Conclusion: Overall, these results confirm that Helichrysum maracandicum polyphenol extracts improve mitochondrial respiration, oxidative phosphorylation efficiency, antioxidant defense, and membrane stability in toxic hepatitis.