Objective: To determine the oxidative stress and endoplasmic reticulum stress and their changes after a-lipoic acid (a-LA) intervention, and to explore the effect and mechanism of fluoride-induced reproductive lesion.
Methods: A total of 40 male Sprague-Dawley (SD) rats were randomly divided into four groups, control group(0.9% sodium chloride), a-LA group(100 mg/kg a-LA), NaF group(25 mg/kg NaF), and NaF+a-LA group(25 mg/kg NaF+100 mg/kg a-LA). Each group was treated in the way of intragastric administration for eight weeks. Sperm quality and the content of NaF in testis were analyzed. The morphologic changes of the testis were observed with the use of HE staining and the apoptosis was detected by the TUNEL assay. Biochemical method was used to measure oxidative stress. Western blot was used to detect the expression of endoplasmic reticulum stress markers, such as GRP78, PERK, and CHOP.
Results: Compared with the control group, the NaF group had a low level in sperm density [(5.99±1.45)×10(6)/ml to (10.96±1.83)×10(6)/ml, P<0.01] and sperm vitality [(33.40±2.71)% vs (66.41±3.33)%, P<0.01], but a high level in sperm abnormality rate [(26.43±2.43)% vs (11.44±1.55)%, P<0.01]. Compared with the NaF group,the NaF+a-LA group had a high level in both sperm density [(8.47±0.82)×10(6)/ml vs (5.99±1.45)×10(6)/ml, P<0.05] and sperm vitality [(49.97±3.51)% vs (33.40±2.71)%, P<0.05], but a low level in sperm abnormality rate [(22.69±2.39)% vs (26.43±2.43)%, P<0.05].There was a significantly higher content of NaF in testis in the NaF group [(11.14±0.77) ug/g vs (5.78±0.28) ug/g, P<0.01] than the control group. Optical microscope was used to observe the morphologic changes of the testis, and it was showed that loose structure appeared both in spermatogenic cells and mature sperm cells while the amount of them decreased. However, after the administration of a-LA, there were complete organelles structure and exfoliated cells in the lumen ameliorated. TUNEL assay found that the apoptotic cells were in a high level in the NaF group [(61.32±7.14)% vs (6.99±2.17)%, P<0.01], while a-LA significantly suppressed the percentage of apoptotic cells in the NaF+a-LA group compared with the Naf group [(45.96±5.31)% vs (61.32±7.14)%, P<0.01].Oxidative stress assays showed that there were higher express of Malondialdehyde(MDA) content [(5.46±0.30) nmol/mgprot vs (3.24±0.58) nmol/mgprot, P<0.01], the activity of Superoxide Dismutase(SOD) [(6.04±0.71) U/mgprot vs (7.19±0.52) U/mgprot, P<0.01] and Glutathione peroxidase(GSH-Px) [(23.67±0.99) U/mgprot vs (26.91±1.67) U/mgprot, P<0.01] in the NaF group than the control group. To compared with the NaF group, the counterpart in the NaF+a-LA group of MDA content was less [(4.66±0.70) nmol/mgprot vs (5.46±0.30) nmol/mgprot, P<0.05] and the GSH-Px activity was high [(25.90±1.93) U/mgprot vs (23.67±0.99) U/mgprot, P<0.05]. Towards the detection of endoplasmic reticulum stress, we found that there were all in higher level in the NaF group that the expression of GRP78 [(0.79±0.05) vs (0.45±0.09), P<0.01], PERK [(0.71±0.04) vs (0.40±0.05), P<0.01], and CHOP[(0.79±0.09) vs (0.19±0.08), P<0.01] than the control group, and to compared with the NaF group, a-LA significantly supressed the expression of GRP78 [(0.46±0.06) vs (0.79±0.05), P<0.01] and CHOP[(0.52±0.09) vs (0.79±0.09), P<0.01].
Conclusion: a-lipoic acid plays a protective role in fluoride-induced reproductive lesion in rats by oxidative stress-mediated endoplasmic reticulum stress.
*Original abstract online at https://pubmed.ncbi.nlm.nih.gov/33342149/
*Information in Chinese at http://journal.yiigle.com/LinkIn.do?linkin_type=DOI&DOI=10.3760/cma.j.cn112137-20200629-01986
Related Studies :
Effects of sodium fluoride and sulfur dioxide on oxidative stress and antioxidant defenses in rat testes
To assess effects of sodium fluoride and sulfur dioxide on oxidative stress and antioxidant defenses in the testes, 96 sexually mature male Wistar rats were divided randomly into four groups of twenty-four rats each. One group of rats was left untreated as controls, and the other three groups were administered,
Testicular toxicity in sodium fluoride treated rats: association with oxidative stress
This study examined the effect of sodium fluoride, a water pollutant important through the world, including India, on testicular steroidogenic and gametogenic activities in relation to testicular oxidative stress in rats. Sodium fluoride treatment at 20mg/kg/day for 29 days by oral gavage resulted in significant diminution in the relative wet
Effect of long-term fluoride exposure on lipid peroxidation and histology of testes in first- and second-generation rats
This experiment was designed to investigate the histological and lipid peroxidation effects of chronic fluorosis on testes tissues of first- and second-generation rats. Sixteen virgin female Wistar rats were mated with eight males (2:1) for approximately 12 h to obtain first-generation rats. Pregnant rats were divided into two groups: controls
Toxic effects of sodium fluoride on reproductive function in male mice
To investigate the effects and possible mechanisms of the action of fluoride on testis cell cycle and cell apoptosis in male mice, sexually mature male Kunming mice were exposed to 50, 100, 200, and 300 mg NaF/L in their drinking water for 8 weeks. At the end of the exposure
Fluoride-elicited developmental testicular toxicity in rats: roles of endoplasmic reticulum stress and inflammatory response
Long-term excessive fluoride intake is known to be toxic and can damage a variety of organs and tissues in the human body. However, the molecular mechanisms underlying fluoride-induced male reproductive toxicity are not well understood. In this study, we used a rat model to simulate the situations of human exposure
Related FAN Content :
Fluoride & Oxidative Stress
A vast body of research demonstrates that fluoride exposure increases oxidative stress. Based on this research, it is believed that fluoride-induced oxidative stress is a key mechanism underlying the various toxic effects associated with fluoride exposure. It is also well established that fluoride's toxic effects can be ameliorated by exposure
Fluoride's Effect on the Male Reproductive System -- In Vitro Studies
Carefully controlled in vitro studies have found that direct exposure of fluoride to the testes or semen inhibits testosterone production and damages sperm. While researchers have known since the 1930s that mega concentrations of fluoride can completely (but reversibly) immobilize sperm, it was not until the 1970s and 1980s that researchers found that relatively modest concentrations of fluoride could cause damage prior to complete immobilization.
Fluoride's Effect on Male Reproductive System - Human Studies
Consistent with in vitro and animal research, studies of human populations have reported associations between fluoride exposure and damage to the male reproductive system. Most notably, a scientist at the Food & Drug Administration reported in 1994 that populations in the United States with more than 3 ppm fluoride in their water had lower "total fertility rates" than populations with lower fluoride levels.
Nutrient Deficiencies Enhance Fluoride Toxicity
It has been known since the 1930s that poor nutrition enhances the toxicity of fluoride. As discussed below, nutrient deficiencies have been specifically linked to increased susceptibility to fluoride-induced tooth damage (dental fluorosis), bone damage (osteomalacia), neurotoxicity (reduced intelligence), and mutagenicity. The nutrients of primary importance appear to be calcium,
Fluoride content in tea and its relationship with tea quality.
J Agric Food Chem. 2004 Jul 14;52(14):4472-6.
Fluoride content in tea and its relationship with tea quality.
Lu Y, Guo WF, Yang XQ.
Department of Tea Science, Zhejiang University, 268 Kaixuan Road, Hangzhou 310027, People's Republic of China.
Abstract: The tea plant is known as a fluorine accumulator. Fluoride (F) content in fresh leaves collected