Potential Protective Effect of Riboflavin Against Pathological Changes in the Main Organs of Male Mice Induced by Fluoride Exposure

Li, Xiang; Yang, Jie; Liang, Chen; Yang, Wei; Zhu, Qianlong; Luo, H; Liu, Xueyan; Wang, Jundong; Zhang, Jianhai

doi:10.1007/s12011-021-02746-7

Cited by 14 publications

(7 citation statements)

References 57 publications

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“…The results of this study show that the fluoride treatment induced hepatopathy because of significant observations of hepatocyte vacuolation and swollen mitochondria, indicating severe ongoing oxidative stress after the fluoride challenge. The findings in this study are consistent with those of previous reports [ 28 , 38 , 39 ]. The interventions of different dosages of TMP alleviated the severity of the hepatocyte damage in the current study, especially in the MT and HT groups.…”

Section: Discussionsupporting

confidence: 94%

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The Pathophysiological Changes and Clinical Effects of Tetramethylpyrazine in ICR Mice with Fluoride-Induced Hepatopathy

Zhang,

Zheng,

et al. 2023

Molecules

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The excessive intake of fluoride, one of the trace elements required to maintain health, leads to liver injury. Tetramethylpyrazine (TMP) is a kind of traditional Chinese medicine monomer with a good antioxidant and hepatoprotective function. The aim of this study was to investigate the effect of TMP on liver injury induced by acute fluorosis. A total of 60 1-month-old male ICR mice were selected. All mice were randomly divided into five groups: a control (K) group, a model (F) group, a low-dose (LT) group, a medium-dose (MT) group, and a high-dose (HT) group. The control and model groups were given distilled water, while 40 mg/kg (LT), 80 mg/kg (MT), or 160 mg/kg (HT) of TMP was fed by gavage for two weeks, with a maximum gavage volume for the mice of 0.2 mL/10 g/d. Except for the control group, all groups were given fluoride (35 mg/kg) by an intraperitoneal injection on the last day of the experiment. The results of this study showed that, compared with the model group, TMP alleviated the pathological changes in the liver induced by the fluoride and improved the ultrastructure of liver cells; TMP significantly decreased the levels of ALT, AST, and MDA (p < 0.05) and increased the levels of T-AOC, T-SOD, and GSH (p < 0.05). The results of mRNA detection showed that TMP significantly increased the mRNA expression levels of Nrf2, HO-1, CAT, GSH-Px, and SOD in the liver compared with the model group (p < 0.05). In conclusion, TMP can inhibit oxidative stress by activating the Nrf2 pathway and alleviate the liver injury induced by fluoride.

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Section: Discussionsupporting

confidence: 94%

“…At the end of the experiment, the brain, heart, liver, kidneys, lungs, and spleen of each subject were collected, weighed, and photographed. The organ index was calculated using the following formula [ 28 ]: Organ index (%) = Organ weight (mg)/body weight (g) × 100% …”

Section: Methodsmentioning

confidence: 99%

The Pathophysiological Changes and Clinical Effects of Tetramethylpyrazine in ICR Mice with Fluoride-Induced Hepatopathy

Zhang,

Zheng,

et al. 2023

Molecules

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“…Previous studies have found that riboflavin may alleviate fluorosis, 27 but it is unknown whether riboflavin has a mitigation effect on the testicular toxicity of fluoride. Our previous studies have shown that IL-17A is a key target of fluoride testicular toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…Riboflavin is a water-soluble vitamin (vitamin B 2 ) with various physiological functions, such as antioxidant, anti-inflammatory, and immune-enhancing functions. − Existing literature shows that riboflavin can attenuate the toxicological damage caused by various compounds. , Riboflavin has been shown to attenuate nigericin-induced macrophage inflammasome activation by inhibiting Caspase-3 . Our preliminary studies found that riboflavin had great potential for mitigating the fluoride-induced damage to the cerebral cortex, ileum, colon, and particularly the epididymis and testes. , However, whether riboflavin can alleviate testicular toxicity caused by fluoride via interleukin 17A-mediated pyroptosis has not been studied.…”

Section: Introductionmentioning

confidence: 86%

“…26 Our preliminary studies found that riboflavin had great potential for mitigating the fluoride-induced damage to the cerebral cortex, ileum, colon, and particularly the epididymis and testes. 27,28 However, whether riboflavin can alleviate testicular toxicity caused by fluoride via interleukin 17A-mediated pyroptosis has not been studied.…”

Section: Introductionmentioning

confidence: 99%

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Riboflavin Attenuates Fluoride-Induced Testicular Injury via Interleukin 17A-Mediated Classical Pyroptosis

Li,

Yang,

Luo

et al. 2024

J. Agric. Food Chem.

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Male reproductive toxicity of fluoride is of great concern worldwide, yet the underlying mechanism is unclear. Pyroptosis is a novel mode of inflammatory cell death, and riboflavin with anti-inflammatory properties has the potential to protect against fluoride damage. However, it is unknown whether pyroptosis is involved in fluoride-induced testicular injury and riboflavin intervention. Here, we first found that riboflavin could alleviate fluoride-caused lower sperm quality and damaged testicular morphology by reducing pyroptosis based on a model of ICR mice treated with NaF (100 mg/L) and/or riboflavin supplementation (40 mg/L) via drinking water for 13 weeks. And then, together with the results of in vitro Leydig cell modelsm it was confirmed that the pyroptosis occurs predominantly through classical NLRP3/Caspase-1/GSDMD pathway. Furthermore, our results reveal that interleukin-17A mediates the process of pyroptosis in testes induced by fluoride and riboflavin attenuation according to the results of our established models of riboflavin-and/or fluoride-treated IL-17A knockout mice. The results not only declare a new mechanism by which fluoride induces testicular injury via interleukin 17A-mediated classical pyroptosis but also provide evidence for the potential clinical application of riboflavin as an effective therapy for fluoride toxicity.

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Fluoride-Induced Cortical Toxicity in Rats: the Role of Excessive Endoplasmic Reticulum Stress and Its Mediated Defective Autophagy

Zhang

Tang

et al. 2022

Biol Trace Elem Res

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Potential Protective Effect of Riboflavin Against Pathological Changes in the Main Organs of Male Mice Induced by Fluoride Exposure

Cited by 14 publications

References 57 publications

The Pathophysiological Changes and Clinical Effects of Tetramethylpyrazine in ICR Mice with Fluoride-Induced Hepatopathy

The Pathophysiological Changes and Clinical Effects of Tetramethylpyrazine in ICR Mice with Fluoride-Induced Hepatopathy

Riboflavin Attenuates Fluoride-Induced Testicular Injury via Interleukin 17A-Mediated Classical Pyroptosis

Fluoride-Induced Cortical Toxicity in Rats: the Role of Excessive Endoplasmic Reticulum Stress and Its Mediated Defective Autophagy

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