scholarly journals Guilingji Protects Against Spermatogenesis Dysfunction From Oxidative Stress via Regulation of MAPK and Apoptotic Signaling Pathways in Immp2l Mutant Mice

2022 ◽  
Vol 12 ◽  
Zhenqing Wang ◽  
Yun Xie ◽  
Haicheng Chen ◽  
Jiahui Yao ◽  
Linyan Lv ◽  

Male infertility is a major health issue with an estimated prevalence of 4.2% of male infertility worldwide. Oxidative stress (OS) is one of the main causes of male infertility, which is characterized by excessive reactive oxygen species (ROS) or lack of antioxidants. Meanwhile, it is reported that oxidative stress plays an important role in the spermatogenic impairment in Inner mitochondrial membrane peptidase 2-like (Immp2l) mutant mice. In this study, we focused on the potential mechanism of Guilingji in protecting the spermatogenic functions in Immp2l mutant mice. The results revealed that Immp2l mutant mice exhibit impaired spermatogenesis and histology shows seminiferous tubules with reduced spermatogenic cells. After administration of Guilingji [150 mg/kg per day intragastric gavage], however, alleviated spermatogenesis impairment and reversed testis histopathological damage and reduced apoptosis. What’s more, western blotting and the levels of redox classic markers revealed that Guilingji can markedly reduce reactive oxygen species. Moreover, Guilingji treatment led to inhibition of the phosphorylation of mitogen-activated protein kinase (MAPK), regulated apoptosis in the cells. In summary, Guilingji can improve spermatogenesis in Immp2l mutant mice by regulating oxidation-antioxidant balance and MAPK pathway. Our data suggests that Guilingji may be a promising and effective antioxidant candidate for the treatment of male infertility.

2021 ◽  
Vol 6 (4) ◽  
pp. 193-198
S. S. Ostrovska ◽  
V. F. Shatorna ◽  
O. G. Slesarenko ◽  
P. G. Gerasymchuk ◽  

Lead does not succumb to biological decomposition, and its ability to accumulate in the body makes it a serious threat to the health of people and animals, while affecting the reproductive function. In most cases, poisoning with lead remains asymptomatic. In a number of studies the authors concluded that in men the level of lead in the blood more than >40 μg/dL leads to the disorder of reproductive functions, such as low libido, a small sperm volume, the amount of spermatozoa, an increase in the abnormal morphology of spermatozoa and decrease in their motility. Male factors are considered the main cause of infertility in 40% of infertile couples and contribute to the emergence of this state in combination with female factors in 20% of cases. The mechanisms of how lead causes male infertility are covered in depth. It is assumed that the basic effect on the reproductive function of men is likely to occur due to changes in the reproductive hormonal axis and hormonal control of spermatogenesis, and not due to direct toxic effects on the seminiferous tubules. The adverse effect of lead on the male reproductive function, especially at low doses (<10 μg/dl), has not been studied properly yet. The risk of lead poisoning is directly connected not only with an increase in concentration, but also with the duration of the impact of metal. There are a number of possible ways of how exposure of lead reduces male fertility. Lead, most likely, impairs the endocrine profile of regulation, mainly through the axis of the hypothalamus-pituitary testosterone, hereafter reduces the production of sperm in the seminiferous tubules of the testicles. At the same time, it acts as an endocrine destroyer, affecting hormones responsible for the production of sperm. In addition to changes in the reproductive hormone axis and hormonal control of spermatogenesis, the activity of enzymes, such as alkaline phosphatase and potassium-sodium ATP-ase, direct toxic effects on the seminiferous tubules, the exposure time of the metal and its dose affect male infertility. Another problem associated with the reproductive toxicity of lead is determined by the excessive generation of the reactive oxygen species. It is known that the oxidative stress caused by lead is involved in the abnormal functions of spermatozoa and male infertility. The possibility to decrease lead level in the body using a number of methods, such as chelatotherapy, nano-encapsulation, use of N-acetylcysteine is considered. Conclusion. Based on animal studies, it seems to be rational to prescribe the corresponding antioxidants to persons suffering from abnormal parameters of spermatozoa and infertility due to the effects of lead. Antioxidants showed a protective effect on spermatogenesis on animal models and reduced reactive oxygen species in sperm and DNA fragmentation in studies in humans. Although there is no final evidence confirming the use of antioxidant additives in men with low fertility to improve fertility rates, it is believed that due to the low cost and a small number of side effects, antioxidants need to be recommended to men with insufficient fertility

2020 ◽  
Vol 3 (2) ◽  
pp. 184-192
Ji Eun Park ◽  
Young Mi Kim

Ultraviolet (UV) irradiation generates reactive oxygen species (ROS) in cells, which induces sunburn cell formation, melanoma, photoaging, and skin cancer. This study examines the anti-photodamage effects of kudzu root vinegar and adenosine in UVB-exposed human keratinocytes (HaCaT cells). UVB significantly decreased HaCaT cell viability, whereas kudzu root vinegar and adenosine did not exhibit cytotoxic effects and increased the viability of HaCaT cells. To investigate the protective effects of kudzu root vinegar and adenosine on UVB-induced oxidative stress in HaCaT cells, ROS, matrix metalloproteinases (MMPs), and mitogen-activated protein kinase (MAPK) were analyzed. UVB-induced treatment reduced the activity of antioxidant enzymes; however, kudzu root vinegar and adenosine increased their activity. These results indicated that kudzu root vinegar and adenosine exert cytoprotective activity against UVB-induced oxidative stress in HaCaT cells. Moreover, they suppressed the UVB-induced downregulation of MMPs and inhibited the phosphorylation of MAPK induced by UVB-irradiation. Therefore, kudzu root vinegar and adenosine offer anti-oxidative effects, via lowering ROS production, suppressing JNK activation, and downregulating expression of MMPs. Our findings suggest that kudzu root vinegar and adenosine have potential application in preventing skin damage owing to UVB exposure. Keywords: reactive oxygen species (ROS), HaCaT cell, UVB, skin damage, anti-aging

1999 ◽  
Vol 14 (11) ◽  
pp. 2801-2807 ◽  
Rakesh K. Sharma ◽  
Fabio F. Pasqualotto ◽  
David R. Nelson ◽  
Anthony J. Thomas ◽  
Ashok Agarwal

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 616 ◽  
Ana Izabel Silva Balbin Villaverde ◽  
Jacob Netherton ◽  
Mark A. Baker

Reactive oxygen species (ROS) can be generated in mammalian cells via both enzymatic and non-enzymatic mechanisms. In sperm cells, while ROS may function as signalling molecules for some physiological pathways, the oxidative stress arising from the ubiquitous production of these compounds has been implicated in the pathogenesis of male infertility. In vitro studies have undoubtedly shown that spermatozoa are indeed susceptible to free radicals. However, many reports correlating ROS with sperm function impairment are based on an oxidative stress scenario created in vitro, lacking a more concrete observation of the real capacity of sperm in the production of ROS. Furthermore, sample contamination by leukocytes and the drawbacks of many dyes and techniques used to measure ROS also greatly impact the reliability of most studies in this field. Therefore, in addition to a careful scrutiny of the data already available, many aspects of the relationship between ROS and sperm physiopathology are still in need of further controlled and solid experiments before any definitive conclusions are drawn.

2021 ◽  
Vol 12 ◽  
Hawa Nordin Siti ◽  
Juriyati Jalil ◽  
Ahmad Yusof Asmadi ◽  
Yusof Kamisah

Cardiac hypertrophy is characteristic of heart failure in patients who have experienced cardiac remodeling. Many medicinal plants, including Parkia speciosa Hassk., have documented cardioprotective effects against such pathologies. This study investigated the activity of P. speciosa empty pod extract against cardiomyocyte hypertrophy in H9c2 cardiomyocytes exposed to angiotensin II (Ang II). In particular, its role in modulating the Ang II/reactive oxygen species/nitric oxide (Ang II/ROS/NO) axis and mitogen-activated protein kinase (MAPK) pathway was examined. Treatment with the extract (12.5, 25, and 50 μg/ml) prevented Ang II-induced increases in cell size, NADPH oxidase activity, B-type natriuretic peptide levels, and reactive oxygen species and reductions in superoxide dismutase activity. These were comparable to the effects of the valsartan positive control. However, the extract did not significantly ameliorate the effects of Ang II on inducible nitric oxide synthase activity and nitric oxide levels, while valsartan did confer such protection. Although the extract decreased the levels of phosphorylated extracellular signal-related kinase, p38, and c-Jun N-terminal kinase, valsartan only decreased phosphorylated c-Jun N-terminal kinase expression. Phytochemical screening identified the flavonoids rutin (1) and quercetin (2) in the extract. These findings suggest that P. speciosa empty pod extract protects against Ang II-induced cardiomyocyte hypertrophy, possibly by modulating the Ang II/ROS/NO axis and MAPK signaling pathway via a mechanism distinct from valsartan.

2004 ◽  
Vol 96 (2) ◽  
pp. 793-801 ◽  
Yong-Jin Lee ◽  
Il-Jun Kang ◽  
Rolf Bünger ◽  
Young-Hee Kang

We recently reported that pyruvate inhibited translocation and activation of p53 caused by DNA damage due to oxidant injury (Lee YJ, Kang IJ, Bünger R, and Kang YH. Microvasc Res 66: 91-101, 2003); this was associated with increased expression of apoptosis-related bcl-2 and decreased expression of bax gene. This study attempted to delineate possible regulatory sites and mechanisms of antiapoptotic pyruvate, focusing on reactive oxygen species-mediated signaling in a human umbilical vein endothelial cell model. We compared the effects of the cytosolic reductant l-lactate and malate-aspartate shuttle blocker aminooxyacetate, both of which increase cytosolic NADH, on the downstream signaling pathway. Hydrogen peroxide (0.5 mM H2O2) depleted intracellular total glutathione that was prevented by pyruvate but not by l-lactate or aminooxyacetate. Activation of caspase-3 and the cleavage of procaspase-6 and procaspase-7 were strongly inhibited by pyruvate but markedly enhanced by l-lactate and aminooxyacetate, implicating redox-related antiapoptotic mechanisms of pyruvate. Western blot analysis and immunochemical data revealed that H2O2-induced transactivation of nuclear factor-κB (NF-κB) was also inhibited by pyruvate but not by l-lactate or aminooxyacetate. In addition, H2O2 downregulated extracellular signal-regulated kinase (ERK1/2) and phosphorylated p38 mitogen-activated protein kinase (MAPK), effects that were fully reversed by pyruvate within 2 h. Collectively, these findings indicate that pyruvate can protect cellular glutathione, thus enhancing cellular antioxidant potential, and that enhanced antioxidant potential can desensitize NF-κB transactivation due to reactive oxygen species, suggesting possible metabolic redox relations to NF-κB. Furthermore, pyruvate blocked the p38 MAPK pathway and activated the ERK pathway in an apparently redox-sensitive manner, which may regulate expression of genes believed to prevent apoptosis and promote cell survival. Thus pyruvate may have therapeutic potential for reducing endothelial dysfunction and improving survival during oxidative stress.

2002 ◽  
Vol 282 (2) ◽  
pp. G300-G306 ◽  
Zuo-Liang Xiao ◽  
Maria J. Pozo Andrada ◽  
Piero Biancani ◽  
Jose Behar

Reactive oxygen species (ROS) have been implicated in the pathogenesis of muscle dysfunction in acute inflammatory processes. The aim of these studies was to determine the effects of ROS on gallbladder muscle function in vitro. Single muscle cells were obtained by enzymatic digestion. H2O2 (70 μM) caused maximal contraction of up to 14% and blocked the response to CCK-8, ACh, and KCl. It did not affect the contractions induced by guanosine 5′- O-(3-thiotriphosphate), diacylglycerol, and inositol 1,4,5-trisphosphate that circumvent membrane receptors. The contraction induced by H2O2 was inhibited by AACOCF3 [cytosolic phospholipase A2(cPLA2) inhibitor], indomethacin (cyclooxygenase inhibitor), chelerythrine [protein kinase C (PKC) inhibitor], or PD-98059 [mitogen-activated protein kinase (MAPK) inhibitor]. H2O2 also reduced the CCK receptor binding capacity from 0.36 ± 0.05 pmol/mg protein (controls) to 0.17 ± 0.03 pmol/mg protein. The level of lipid peroxidation as well as the PGE2 content was significantly increased after H2O2 pretreatment. Unlike superoxide dismutase, the free radical scavenger catalase prevented the H2O2 induced contraction, and its inhibition of the CCK-8 induced contraction. It is concluded that ROS cause damage to the plasma membrane of the gallbladder muscle and contraction through the generation of PGE2 induced by cPLA2-cyclooxygenase and probably mediated by the PKC-MAPK pathway.

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Huimin Li ◽  
Jing Chen ◽  
Chaomei Xiong ◽  
Han Wei ◽  
Changchang Yin ◽  

Arachniodes exilisis used as a folk medicine in China and proved to have antibacterial, anti-inflammatory, and sedative activities. In the present study, the antitumor effect of the total flavonoids ofA. exilis(TFAE) against HepG2 cells was evaluated. The results showed that TFAE inhibited the growth of HepG2 cells in a dosage- and time-dependent manner. Flow cytometry and Hoechst 33342 fluorescence staining results showed that TFAE could significantly increase the apoptosis ratio of HepG2 cells, which is accompanied with increased intracellular reactive oxygen species (ROS) production and decreased mitochondrial membrane potential(ΔΨm). Western blotting indicated that TFAE downregulated the ratio of Bcl-2/Bax, increased cytochrome c release, and activated the caspases-3 and -9. Further analysis showed that TFAE stimulated the mitogen-activated protein kinase (MAPK). However, treatment with NAC (reactive oxygen species scavenger) and MAPK-specific inhibitors (SP600125 and SB203580) could reverse the changes of these apoptotic-related proteins. These results suggested that TFAE possessed potential anticancer activity in HepG2 cells through ROS-mediated mitochondrial dysfunction involving MAPK pathway.

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

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