Abstract
The mutagenic and carcinogenic heterocyclic amine, 2-amino-3-methylimidazo-[4,5-f]-quinoline (IQ), is produced while cooking protein-rich foods. Mesenchymal stem cells (MSCs) (as cell-based therapy) and Annona muricata (graviola) (as a natural product) both possess preventive capacities against free radical toxicity in various tissues. This study aims to compare the therapeutic properties and effects of AD-MSCs and graviola on IQ-induced liver toxicity and DNA damage in rats. Sixty adult male rats were divided into four groups: normal unexposed control, IQ, IQ + graviola, and IQ + AD-MSCs. After 6 weeks, the rats were sacrificed, and liver tissues were examined for histopathological changes using hematoxylin-eosin staining. p53 protein expression was evaluated by immunohistochemistry, and DNA damage was measured by using the comet test. Our findings indicated that AD-MSC therapy led to the most significant improvement in DNA damage, apoptosis, and p53, LPO, AST, and ALT levels caused by IQ toxicity. Additionally, AD-MSCs reduced severe histological alterations (damage and fibrosis) in liver cells induced by IQ. However, the effectiveness of graviola treatment is limited, severely restricting its use for chronic liver toxicity. In conclusion, the initial stage of IQ-induced liver toxicity is caused by oxidative stress-induced DNA damage. Compared with graviola, AD-MSCs exhibit more potent therapeutic effects against IQ-induced liver damage.