Abstract

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

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