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Pendimethalin-induced oxidative stress, DNA damage and activation of anti-inflammatory and apoptotic markers in male rats.

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-?, TNF-? 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.

SUBMITTER: Ahmad MI

PROVIDER: S-EPMC6244357 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Pendimethalin-induced oxidative stress, DNA damage and activation of anti-inflammatory and apoptotic markers in male rats.

Ahmad Md Irshad MI Zafeer Mohd Faraz MF Javed Mehjbeen M Ahmad Masood M

Scientific reports 20181120 1

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 ( ...[more]

PMID: 30459330

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Project description:Monosodium glutamate (MSG) is a widely used food additive, and there is a trepidation that MSG plays a critical role in multiple hepatic disorders. This study was planned to investigate Graviola extract (GE) effects on hepatic and cellular alterations induced by MSG. Fifty Wistar rats were randomly allocated into five groups: control (received normal saline), Graviola (received 200 mg/kg body weight), MSG (received 2.4 gm MSG/kg, 15% of Lethal dose (LD50) of MSG), Graviola + monosodium glutamate (MSG + GE; received GE, 200 mg/kg/day and MSG 2.4 gm/kg body weight (BW) for the next four weeks), and monosodium glutamate + Graviola (received MSG only (2.4 gm/kg BW) daily for four weeks, then concomitant with Graviola (200 mg/kg BW) daily for the next four weeks. MSG and GR were administered orally for eight weeks. Our results showed that MSG caused a significant increase in oxidative stress markers malondialdehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO), hydrogen peroxide (H2O2), proinflammatory cytokines interleukin 6 (IL-6) level, a tumor protein (P53), hepatic cellular damage, as well as proapoptotic markers caspase-3, and B-cell lymphoma 2 (BCL-2)-like protein 4 (Bax). A significant decrease in superoxide dismutase (SOD), catalase (CAT), glutathione S transferase (GST), reduced glutathione (GSH), and an antiapoptotic agent B-cell lymphoma 2 (BCl-2) was observed. The detected MSG effects were normalized by Graviola administration, either a prophylactic or protecting dose. Besides, Graviola reduced the expression of inducible nitric oxide synthase (iNOS) and hepatic fatty acid synthase (FAS) and led to the upregulation of the silent information regulator protein one gene expression gene (SIRT1).In conclusion, the results suggest that Gaviola's interrelated antiapoptotic, antioxidant, and anti-inflammatory properties are potential mechanisms to enhance hepatic deficits and protect the liver. Graviola can, therefore, be considered a promising hepatoprotective supplement. Additionally, further human clinical trials are also necessary to validate the present research.

Dataset Information

Pendimethalin-induced oxidative stress, DNA damage and activation of anti-inflammatory and apoptotic markers in male rats.

Publications

Pendimethalin-induced oxidative stress, DNA damage and activation of anti-inflammatory and apoptotic markers in male rats.

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