Inactivation of Mst/Nrf2/Keap1 signaling flexibly mitigates MAPK/NQO-HO1 activation in the reproductive axis of experimental fluorosis.

Fluoride induced reprotoxicity through oxidative stress-mediated reproductive cell death. Hence, the current study evaluated the importance of the MST/Nrf2/MAPK/NQO-HO1 signaling pathway in fluorosis-induced reproductive toxicity. For this purpose, the reproductive toxicity of sodium fluoride (NaF) at physiological, biochemical, and intracellular levels was evaluated. In-vivo, NaF at 100 mg/L instigated physiological dysfunction, morphological, stereological, and structural injuries in the gut-gonadal axis of fluorosis mice through weakening the antioxidant signaling, Nrf2/HO-1/NQO1signaling pathway, causing the gut-gonadal barrier disintegrated via oxidative stress-induced inflammation, mitochondrial damage, apoptosis, and autophagy. Similar trends were also observed in-vitro in the isolated Leydig cells (LCs) challenging with 20 mg/L NaF. Henceforth, activating the cellular antioxidant signaling pathway, Nrf2/HO-1/NQO1, inactivating autophagy and apoptosis, or attenuating lipopolysaccharide (LPS) can be the theoretical basis and valuable therapeutic targets for coping with NaF-induced reproductive toxicity.

Molybdenum-Induced Apoptosis of Splenocytes and Thymocytes and Changes of Peripheral Blood in Sheep.

To investigate the effects of molybdenum (Mo) on apoptosis of lymphocytes and changes of peripheral blood in sheep, a total of 20 5-month-old healthy female sheep were randomly divided into five groups of 4 and orally administered with water containing Na2MoO4·2H2O (0, 5, 10, 20, and 50 mg/kg BW/day) for 28 days. Jugular vein blood was taken on the 0th, 7th, 14th, 21st, and 28th day of Mo treatment, respectively. On the 28th day, the spleen and thymus were removed for observing histopathology and apoptosis-related DNA damage by hematoxylin and eosin (HE) staining and TdT­mediated dUTP Nick-End Labeling (TUNEL) staining, respectively. The blood routine indexes were determined by an automatic blood analyzer. Further, the apoptosis of lymphocytes and changes in mitochondrial membrane potential (MMP) of peripheral blood were analyzed by flow cytometry. Results showed that excessive Mo induced apoptosis-related DNA damage in the splenocytes and thymocytes and significantly increased the apoptosis indexes of the splenocytes and thymocytes (P < 0.01). Furthermore, the treatment with excessive Mo significantly decreased the MMP (P < 0.01) and promoted apoptosis in peripheral blood lymphocytes (P < 0.01). And the number of WBC, Lymph, Gran, and RBC and the indexes of HGB and HCT were also significantly decreased (P < 0.05 or P < 0.01), while RDW was significantly increased by excessive Mo (P < 0.05 or P < 0.01). In conclusion, excessive Mo-induced DNA damage and apoptosis of the lymphocytes changed the RBC-related indexes of the peripheral blood in sheep.