The widely used herbicide atrazine (ATR) can cause many adverse effects including immunotoxicity, but the underlying mechanisms are not fully understood. The current study investigated the role of oxidative stress and calcium homeostasis in ATR-induced immunotoxicity in mice. ATR at doses of 0, 100, 200, or 400 mg/kg body weight was administered to Balb/c mice daily for 21 days by oral gavage. The studies performed 24 hr after the final exposure showed that ATR could induce the generation of reactive oxygen species in the spleen of the mice, increase the level of advanced oxidation protein product (AOPP) in the host serum, and cause the depletion of reduced glutathione in the serum, each in a dose-related manner. In addition, DNA damage was observed in isolated splenocytes as evidenced by increase in DNA comet tail formation. ATR exposure also caused increases in intracellular Ca2+ within splenocytes. Moreover, ATR treatment led to increased expression of genes for some antioxidant enzymes, such as HO-1 and Gpx1, as well as increased expression of NF-κB and Ref-1 proteins in the spleen. In conclusion, it appears that oxidative stress and disruptions in calcium homeostasis might play an important role in the induction of immunotoxicity in mice by ATR.
The present study aimed to investigate the protective effects of etomidate on hyperoxia-induced acute lung injury in mice, particularly on the nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. Fifty specific pathogen-free mice were randomly divided into the blank control, model, high oxygen exposure + low etomidate dose (0.3 mg•kg -1 ), a high oxygen exposure + moderate etomidate dose (3 mg•kg -1 ), and a high oxygen exposure + high etomidate dose (10 mg•kg -1 ) groups, with ten mice allotted per group. After 72 h, the mice were sacrificed and the lung tissues were harvested, and the wet-to-dry (W/D) ratio of the tissues was calculated. Hematoxylin-eosin staining was performed to observe the pathological changes in the lung tissues, and the lung injury score (LIS) was calculated. The mRNA and protein expression levels of Nrf2 and HO-1 were measured. The malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) levels were also measured, and interleukin (IL)-1β, IL-6, tumor necrosis factor alpha (TNF-α) and IL-10 concentrations in the bronchoalveolar lavage fluid were determined. At low and moderate doses, etomidate decreased pathological damage in the lung tissue, decreased the LIS and W/D ratio, upregulated Nrf2 and HO-1 mRNA and protein expression, decreased IL-1β, IL-6, and TNF-α concentrations, increased MPO activity and IL-10 levels, suppressed the production of the oxidation product MDA, and enhanced the activities of the antioxidant enzymes CAT and SOD. Within a certain dose range, etomidate enhanced antioxidant and anti-inflammatory effects in mice, thereby decreasing lung injury induced by the chronic inhalation of oxygen at high concentrations. Furthermore, the underlying mechanism may be associate with the upregulation of the Nrf2/HO-1 signaling pathway.
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