Fungicides Mancozeb, Carbendazim, and Hymexazol Induce Dose-Dependent Pulmonary Toxicity via Oxidative Stress and NF-κB Activation in Rats

Pesticide exposure is a significant public health concern, with fungicides like Mancozeb, carbendazim, and hymexazol widely used globally in agriculture and veterinary fields. While their general toxicity is known, a comparative understanding of their specific impact on pulmonary health and underlying mechanisms remains crucial. Current safety assessments often lack detailed insights into how these compounds differentially induce lung injury, particularly concerning oxidative stress and inflammatory pathways. This study addresses this gap by directly comparing the pulmonary toxicity profiles of these three common fungicides.

Researchers conducted a 14-day comparative study on 35 rats divided into 7 groups. Animals received daily oral gavage of either vehicle (control) or one of three fungicides: Mancozeb (125 mg/kg or 250 mg/kg), carbendazim (125 mg/kg or 250 mg/kg), or hymexazol (75 mg/kg or 150 mg/kg). Primary endpoints included biochemical analysis of MDA (malondialdehyde) and GSH (glutathione) levels in lung tissue homogenates, qPCR for IL1β, TNFα, and NF-κB mRNA expression, Western blot for iNOS and Cox-2 protein expression, and comprehensive histopathological examination of pulmonary tissues.

All tested fungicides, Mancozeb, carbendazim, and hymexazol, dose-dependently induced significant pulmonary toxicity in rats. Lung tissue homogenates consistently showed increased malondialdehyde (MDA) levels and decreased glutathione (GSH) content across all treatment groups compared to controls, indicating heightened oxidative stress. > The highest pulmonary toxicity was consistently observed in the hymexazol groups, followed by Mancozeb and then carbendazim, indicating a clear hierarchy of detrimental effects. Molecular analysis revealed a dose-dependent upregulation of mRNA levels for key pro-inflammatory genes including IL1β, TNFα, and NF-κB. Furthermore, strong protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2) were detected, confirming a robust inflammatory response. These biochemical and molecular changes were corroborated by severe histopathological alterations observed within the pulmonary tissues, consistent with significant lung damage. The findings collectively suggest that oral intake of these fungicides triggers pulmonary toxicity primarily through oxidative stress, which subsequently activates the NF-κB signaling pathway.