Abstract
Male Wistar rats were exposed to herbicide, pendimethalin (PND) at varying oral doses of 62.5, 125 and 250 mg/kg b.w. for 14 days. Toxiological effects were assessed in terms of oxidative stress, DNA damage, histopathological alterations and induction of anti-inflammatory and apoptotic responses linked Bax, Bcl-2, IFN-γ, TNF-α and caspase-3 gene expression. In comparison with respective untreated controls, all exposure groups of PND exhibited significant changes in the oxidative stress markers (protein carbonylation and lipid peroxidation) and antioxidant defenses (GSH, SOD, CAT and GST) in liver and kidney tissues. The histopathological changes including leucocyte infiltration, pyknotic nuclei, necrosis, large bowman’s space, shrinked renal cortex, were observed in the liver and kidney tissues of PND exposed rats. Significant DNA damage was recorded through comet assay in liver and kidney cells of treated animals as compared to control. Alteration in anti-inflammatory and apoptotic genes expression determined by RT-PCR, revealed the activation of intrinsic apoptotic pathway(s) under the PND induced cellular stress. A pronounced increase in Bax expression, caspase-3 activities and decreased Bcl-2 expressions were also associated with PND-induced apoptosis. Data from this study suggests that PND induces cellular toxicity and genetic perturbations which can alter the normal cellular and physiological functioning in rats.
Highlights
Pendimethalin (PND) is a member of dinitroaniline herbicide
As a matter of fact, there is no substantial amount of literature available on the cytotoxicity or genotoxicity associated with harmful oxidative effects caused by chronic exposure of pendimethalin in rats
Reduction in Superoxide dismutase (SOD) and CAT activities was recorded to be 2.40 and 3.12 folds respectively in liver whereas 1.70 and 2.45 folds in kidney comparing with their respective controls
Summary
Effects of PND on oxidative stress markers. Administration of PND at low, middle and high doses significantly enhanced the protein carbonyl content and lipid peroxidation (LPO) in rat liver and kidney in a concentration-dependent manner (Fig. 1a and b). Treatment of rats with different concentrations of PND resulted in a manifest up regulation of anti-inflammatory and apoptosis markers, TNF-α, IFN-γ, Bax and Caspases-3 as well as down-regulation of Bcl-2 as compared to respective control group in a dose dependent manner. Previous studies on organic pollutants and pesticides have shown the activation of caspase-3, and their role in inducing apoptosis, which corroborates our results[43,44,45] These findings suggest that IFN-γ and TNF-α, independently or synergistically, are able to increased Bax expression and suppress Bcl-2 expression, resulting in increased formation of Bax homodimers[46]. The results of our molecular biological work lead us to conclude that pendimethalin is capable of inducing cellular and genetic toxicities, which manifest as disturbances in oxidative and anti-oxidative balance, DNA damage, histopathological anomalies, activation of apoptosis related Bax, Bcl-2 and caspase-3 genes in treated male rats
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