This study evaluated the oxidative stress response and histopathological alterations in liver and kidney tissues of rats exposed to dichlorvos, dimethoate, cypermethrin, and their combinations over 28 days. Malondialdehyde (MDA) levels, catalase (CAT), and superoxide dismutase (SOD) activities were assessed as biomarkers of lipid peroxidation and antioxidant defence, alongside histological examinations. Liver MDA concentrations significantly increased from 3.2 nmol/g in control (Group A) to 7.5 nmol/g in the triple combination group (Group H), indicating severe lipid peroxidation. Similarly, kidney MDA levels rose from 2.9 nmol/g (Group A) to 7.3 nmol/g (Group H), confirming systemic oxidative stress. CAT activity in liver tissues increased progressively, with Group H recording the highest activity at 0.125 ± 0.002 U/mg protein compared to 0.045 ± 0.002 U/mg in the control. In the kidney, CAT activity escalated from 0.032 ± 0.002 U/mg protein in controls to 0.182 ± 0.002 U/mg in Group H. SOD activity followed a similar trend. Liver SOD levels increased from 0.030 ± 0.001 U/mg protein in Group A to 0.167 ± 0.002 U/mg protein in Group H, while kidney SOD rose from 0.38 ± 0.01 U/mg protein in controls to a peak of 4.38 ± 0.04 U/mg in Group H, reflecting pronounced antioxidant activation. Histopathological analyses revealed progressive hepatocellular degeneration, periportal inflammation, and vascular congestion, with Group H exhibiting hepatocellular vacuolation and necrosis. In kidneys, lesions ranged from glomerular atrophy and tubular necrosis in single exposures to extensive tubular damage and glomerular alterations in Group H. These findings underscore a dose-dependent and synergistic toxic interaction of these pesticides, warranting regulatory attention to mixture exposures. The study advocates integrating oxidative biomarkers and histopathological evaluations for comprehensive pesticide risk assessments.

Keywords: Oxidative Stress, Pesticide Mixtures, Organophosphates, Pyrethroids, Dichlorvos, Dimethoate, Cypermethrin, Liver Toxicity, Kidney Injury, Malondialdehyde (MDA), Superoxide Dismutase (SOD), Catalase (CAT).

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Source of Funding:

This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Competing Interests Statement:

The authors declare that they have no competing interests related to this work.

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The authors declare that they consented to the publication of this study.

Authors' contributions:

Both the authors took part in literature review, analysis, and manuscript writing equally.

Availability of data and materials:

Supplementary information is available from the authors upon reasonable request.

Institutional Review Board Statement:

Not applicable for this study.

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Not applicable for this study.