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 :
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
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,
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
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
NADPH oxidase participates in the oxidative damage caused by fluoride in rat spermatozoa. Protective role of a-tocopherol
Fluorosis, caused by drinking water contaminated with inorganic fluoride, is a public health problem in many areas around the world. The aim of this study was to evaluate oxidative stress in spermatozoa caused by fluoride and NADPH oxidase in relationship to fluoride. Four experimental groups of male Wistar rats were
Related FAN Content :
Fluoride's Effect on Male Reproductive System -- The "Sprando/Collins" Anomaly
In contrast to the findings of over 60 animal studies from other research teams, a series of studies by FDA researchers Sprando & Collins reported virtually no evidence of reproductive toxicity among animals treated with very high levels of fluoride exposure. The reasons for this discrepancy remains unclear.
Excerpts from Sprando/Collins' Studies:
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 & 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 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
Fluoride's Effect on Male Reproductive System: Animal Studies
Over 60 studies on animals (including rats, mice, roosters, and rabbits) have found that fluoride adversely impacts the male reproductive system. These studies have repeatedly found the following effects: (1) decreases in testosterone levels; (2) reduced sperm motility; (3) altered sperm morphology; (4) reduced sperm quantity; (5) increased oxidative stress; (6) and reduced capacity to breed.