Nutraceutical Synergy: Unraveling the Protective Effects of Methyl Gallate and Chia Seed Oil in Doxorubicin-induced Hepatic Injury and Bax/Bcl2 Imbalance

BACKGROUND: Nutraceuticals like methyl gallate and chia seed oil are gaining global attention for their therapeutic potential. This study investigates their effects on hepatocyte apoptosis and liver architecture in a doxorubicin-induced hepatotoxicity model, utilizing techniques such as TUNEL assay, immunohistochemistry (Bax & Bcl2), H&E staining, and scanning electron microscopy. METHODOLOGY: Thirty female Wistar rats were divided into five groups (n=6): Group I (Normal healthy control), Group II (Doxorubicin-intoxicated control), Group III (Doxorubicin-intoxicated + methyl gallate), Group IV (Doxorubicin-intoxicated + chia seed oil), and Group V (Doxorubicin-intoxicated + both). Liver function tests, histology, and cell apoptosis analysis were performed to assess the effects. RESULTS: Doxorubicin-intoxicated rats (Group II) exhibited significantly elevated ALT, AST, and ALP levels (p < 0.001) and severe hepatic damage compared to controls. Group III and Group IV showed significant reductions in liver enzyme levels (p < 0.05 and p < 0.01, respectively), while Group V demonstrated the most significant decrease (p < 0.001). Immunohistochemistry revealed increased Bax and decreased Bcl2 expression in Group II (p < 0.001), which improved significantly with methyl gallate, chia seed oil, and their combination (p < 0.05 to p < 0.001). TUNEL assay showed reduced apoptotic index in treatment groups, with Group V showing the most significant reduction (p < 0.001). Scanning electron microscope (SEM) analysis confirmed restoration of hepatocyte architecture, especially in Group V. CONCLUSION: Methyl gallate and chia seed oil, individually and in combination, demonstrated significant hepatoprotective effects against doxorubicin-induced hepatotoxicity, with the combination showing the greatest efficacy. These nutraceuticals hold promise as adjunct therapies to reduce doxorubicin-induced liver injury.