Pharmacological Research - Natural Products, vol.10, 2026 (Scopus)
This study investigated the protective role of Curcuma longa L. extract (curcumin, CMN) against cypermethrin (CYP)-induced hepatic and renal injury in male albino rabbits. Animals were divided into four groups: control, CYP (25 mg kg⁻¹), CMN (50 mg kg⁻¹), and combined CYP + CMN, treated orally for 45 days. CYP administration markedly reduced hepatic and renal antioxidant enzymes, including SOD (47 %), CAT (39 %), and GPx (42 %), while elevating lipid peroxidation (61 %) and serum markers of liver (ALT 2.6-fold, AST 2.3-fold, ALP 2.1-fold) and kidney dysfunction was also increased (urea 58 %, creatinine 52 %). Co-treatment with CMN significantly restored antioxidant enzyme activities toward control levels (p < 0.01), normalized lipid profile indices, and improved histopathological architecture of hepatic and renal tissues. To complement experimental results, a computational regression model was trained on data to identify major predictors of CYP-induced oxidative stress. Binary classification model was developed to distinguish CYP-exposed (toxic) from CMN-protected (non-toxic) conditions using the same biochemical and enzymatic feature set. The classifier achieved outstanding performance, with overall accuracy of 100 %, area under the ROC curve (AUC = 1.0), precision (0.96), and recall (0.94), confirming a clear separation between the two physiological states. The Random forest model showed high predictive accuracy (R² = 0.98, RMSE = 29.20, MAPE = 1.1 %) The most discriminative predictors included SOD, GPX, and VLDL, of liver which consistently ranked among the top features in both regression and classification analyses. These results reinforce the experimental observations that hepatic antioxidant enzymes and lipid-associated parameters serve as reliable biomarkers for distinguishing oxidative injury from curcumin-mediated protection.