The Effect of Chenopodium quinoa Willd. Extract on DMH‐Induced Colorectal Cancer and Hepatic Oxidative Stress Through Monitoring PI3K/Akt/mTOR Pathway

Objective Dimethylhydrazine (DMH), a powerful inducer of colorectal cancer (CRC) in animal models, is known for its hepatotoxic effect through the generation of reactive oxygen species upon its metabolic processing. Chenopodium quinoa is a well‐documented medicinal herb known for its powerful antioxidant, antitumor, and anti‐inflammatory activities. This study aimed at investigating the protective role of aqueous quinoa extract on DMH‐induced hepatic oxidative stress and modulation of the phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway during colon carcinogenesis in male Balb/c mice. Methods Mice were randomly divided into eight experimental groups of 6 mice each. CRC was induced with DMH (20 mg/kg). Mice were either pretreated or post‐treated with quinoa aqueous extract orally by gavage at a dose of 250 mg/kg for 12 or 8 weeks (5 days/week). Assessments included histopathological liver examination, molecular quantification of mRNA levels of some key players of the PI3K/AKT/mTOR pathway (platelet‐derived growth factor‐BB [ PDGF-BB ],​ platelet‐derived growth factor receptor Beta [ PDGFR-β ] , mTOR ) by quantitative reverse transcription polymerase chain reaction (qRT‐PCR), biochemical measure of catalase (CAT) and superoxide dismutase (SOD) by enzyme‐linked immunosorbent assay (ELISA), and a blood test measuring the level of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes as well as malondialdehyde (MDA) level. All statistical analyses were performed using Microsoft Excel, with results expressed as mean ± standard deviation. One‐way ANOVA was used to assess differences between groups, with p < 0.05 considered statistically significant. Graphs were generated with GraphPad Prism. Results Results showed that quinoa pretreatment significantly reduced liver cell necrosis, inflammation, and histoarchitectural damage caused by DMH. Quinoa pretreatment also mitigated DMH‐induced elevation of AST, ALT, MDA, and CAT levels, while restoring SOD activities in both regimens of administration. Molecular analyses revealed that DMH increased PDGF-BB , PDGFR-β , and mTOR gene expression, which was significantly downregulated by quinoa extract. Conclusion In conclusion, quinoa aqueous extract demonstrated hepatoprotective and antioxidant effects by reducing oxidative stress and modulating key molecular pathways associated with CRC development, supporting its potential as a natural dietary chemopreventive agent.