Folic acid protects against fluoride-induced oxidative stress and testicular damage in rats

Objective:To investigate the effects of folic acid on testicular oxidative damage in sodium fluoride-induced male Wistar rats.Methods:A total of 24 male Wistar rats were divided into 4 groups:the control,sodium fluoride(fed with 100 mg/L sodium fluoride through drinking water orally for 21 days),folic acid(36μg/kg body weight/day,orally),and sodium fluoride plus folic acid(received similar dose orally)groups.At the end of 21 days,epididymal sperm parameters,biochemical analysis of testicular tissue,and serum hormonal levels were performed along with histopathological studies.Results:Sodium fluoride intoxication resulted in marked reduction in gonado somatic index,serum luteinizing hormone,and testosterone level along with 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase activities.In addition,reduction in sperm density,as well as loss of sperm motility and sperm viability,were also observed.Besides,increased levels of testicular malondialdehyde,nitrite,interleukin-6 and tumor necrosis factor-α as well as decreased levels of superoxide dismutase and catalase activities and reduced glutathione content were found to be associated with this toxicity.Folic acid co-treatment,on the other hand,could prevent all the sodium fluoride-induced testicular pathophysiology and oxidative stress related parameters.Histological examinations of testicular sections from the experimental rats supported these results.Conclusions:Combining all,this study suggests that being an antioxidant,folic acid plays a beneficial role against fluoride-induced adverse effects on the male reproductive system.

Potential role of punicalagin against oxidative stress nduced testicular damage

Punlcalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin （purity L〉98%） on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide （LPS） induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin （PU） against oxidative stress-induced infertility. Results demonstrated that 9 mg kg-1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU ＋ LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.

Antioxidant activity and protective effect of Clitoria ternatea flower extract on testicular damage induced by ketoconazole in rats

Background： Ketoconazole （KET）, an antifungal drug, has adverse effects on the male reproductive system. Pre-treatments with antioxidant plant against testicular damage induced by KET are required. The flowers of Clitoria tematea （CT） are proven to have hepatoprotective potential. However, the protective effect on KET-induced testicular damage has not been reported. Objective： To investigate the protective effect of CT flower extracts with antioxidant activity on male reproductive parameters including sperm concentration, serum testosterone level, histopathology of the testis, and testicular tyrosine phosphorylation levels in rats induced with KET. Methods： The antioxidant activity of CT flower extracts was determined using 2,2-diphenyl-1-picrylhydrazyl （DPPH） and ferric reducing antioxidant power （FRAP） assays. Male rats were treated with CT flower extracts （10, 50, or 100 mg/kg BW） or distilled water via a gastric tube for 28 d （preventive period： Days 1-21） and induced by KET （100 mg/kg BW） via intraperitoneal injection for 7 d （induction period： Days 22-28）. After the experiment, all animals were examined for the weights of the testis, epididymis plus vas deferens and seminal vesicle, serum testosterone levels, sperm concentration, histological structures and diameter of testis, and testicular tyrosine phosphorylation levels by immunoblotting. Results： The CT flower extracts had capabilities for DPPH scavenging and high reducing power. At 100 mg/kg BW, the extract had no toxic effects on the male reproductive system. Significantly, in CT＋KET groups, CT flower extracts （50 and 100 mg/kg BW） alleviated the reduction of reproductive organ weight parameters, testosterone levels, and sperm concentration. In addition, CT flower extracts gave protection from testicular damage in KET-induced rats. Moreover, in the CT100＋KET group, CT flower extracts significantly enhanced the expression of a testicular 50-kDa tyrosine phosphorylated protein compared with that of other groups. Conclusions： C. ternatea flower extracts possessing antioxidant activity are not harmful to the male reproductive system and can protect against testicular damage in KET-induced rats.

Phyllanthus emblica leaf extract ameliorates testicular damage in rats with chronic stress

Stress affects the male reproductive system and can cause sub-fertility or infertility. Although Phyllanthus emblica L.(PE) extract has been shown to have high antioxidant capacity and protective properties in damaged tissue, the preventive effects of PE extract on testicular function from stress-related impairment have never been demonstrated. This study aimed to investigate the effects of PE aqueous leaf extract on testicular impairment and protein marker changes in rats suffering from chronic stress. Adult male rats were divided into four groups: a control group, a chronic stress(CS) group, and two groups with CS that received different doses of PE extract(50 or 100 mg/kg body weight(BW)). In the treatment groups, the animals were given PE extract daily before stress induction for 42 consecutive days. Stress was induced through immobilization(4 h/d) followed by forced cold swimming(15 min/d). Sperm quality and the histology of the testes and caudal epididymis were examined, as were levels of serum corticosterone, testosterone, and malondialdehyde(MDA). The expressions of testicular steroidogenic acute regulatory(StAR) and tyrosine-phosphorylated proteins were investigated using immuno-Western blot analysis, as these proteins are assumed to play important roles in spermatogenesis and androgen synthesis. The results showed that PE(50 mg/kg BW) significantly increased sperm concentration and testosterone levels, while decreasing corticosterone levels, MDA levels, sperm head abnormalities, and acrosome-reacted sperm in CS rats. In addition, PE at both doses was found to diminish testicular histopathology in the CS rats. We also found that 50 mg/kg BW of PE significantly improved StAR protein expression and altered the intensities of some tyrosine-phosphorylated proteins in testis. We conclude that PE leaf extract at 50 mg/kg BW can prevent testicular damage in rats with CS.

The calcium-sensing receptor participates in testicular damage in streptozotocin-induced diabetic rats

Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor （CaSR） is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin （STZ, 40 mg kg-1） in Wistar rats. Animals then received GdCl3 （an agonist of CaSR, 8.67 mg kg-1）, NPS-2390 （an antagonist of CaSR, 0.20 g kg-~）, or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde （MDA）, lower superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH2-terminal protein kinase （JNK）, p38, and extracellular signaling-regulated kinase （ERK） 1/2. The above parameters could be further increased or aggravated by the administration of GdCI3, but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men.

The in-vivo assessment of Turkish propolis and its nano form on testicular damage induced by cisplatin

Objective: Chemotherapeutic drugs, such as cisplatin(CP), which are associated with oxidative stress and apoptosis, may adversely affect the reproductive system. This study tests whether administration of propolis and nano-propolis(NP) can alleviate oxidative stress and apoptosis in rats with testicular damage induced by CP.Methods: In this study, polymeric nanoparticles including propolis were synthesized with a green sonication method and characterized using Fourier transform-infrared spectroscopy, Brunauer-EmmettTeller, and wet scanning transmission electron microscopy techniques. In total, 56 rats were divided into the following seven groups: control, CP, propolis, NP-10, CP + propolis, CP + NP-10, and CP + NP-30.Propolis(100 mg/kg), NP-10(10 mg/kg), and NP-30(30 mg/kg) treatments were administered by gavage daily for 21 d, and CP(3 mg/kg) was administered intraperitoneally in a single dose. After the experiment,oxidative stress parameters, namely, malondialdehyde(MDA), glutathione(GSH), glutathione peroxidase(GPx), and catalase(CAT), and apoptotic pathways including B cell leukemia/lymphoma-2 protein(Bcl-2)and Bcl-2-associated X protein(Bax) were measured in testicular tissues. Furthermore, sperm quality and weights of the testis, epididymis, right cauda epididymis, seminal vesicles and prostate were evaluated.Results: Propolis and NP(especially NP-30) were able to preserve oxidative balance(decreased MDA levels and increased GSH, CAT, and GPx activities) and activate apoptotic pathways(decreased Bax and increased Bcl-2) in the testes of CP-treated rats. Sperm motility in the control, CP, and CP + NP-30 groups were 60%, 48.75%, and 78%, respectively(P<0.001). Especially, NP-30 application completely corrected the deterioration in sperm features induced by CP.Conclusion: The results show that propolis and NP treatments mitigated the side effects of CP on spermatogenic activity, antioxidant situation, and apoptosis in rats.

The leaf extracts of Camellia sinensis (green tea) ameliorate sodium fluoride-induced oxidative stress and testicular dysfunction in rats

Objective:To investigate the effect of Camellia(C.)sinensis in mitigating oxidative damage and reproductive toxicity in testis induced by sodium fluoride in a rat model.Methods:Twenty-four adult male Wister rats were divided into 4 groups,with 6 rats in each group.Group 1 orally received distilled water(1 mL/100 g body weight)daily and served as the control group,while group 2 received drinking water with 100 ppm sodium fluoride per day for 21 consecutive days,group 3 was administered with only C.sinensis extract by gavage at a dose of 100 mg/kg body weight and group 4 received drinking water with 100 ppm sodium fluoride and 100 mg/kg body weight C.sinensis leaf extract per day for 21 consecutive days.At the end of the treatment,the rats were sacrificed under light ether anesthesia.The gonado-somatic index,sperm count and motility,serum level of luteinizing hormone and testosterone were assayed.Lipid peroxidation[malondialdehyde(MDA)level],nitric oxide(NO)production,and activities of antioxidant enzymes-superoxide dismutase(SOD),catalase,and reduced glutathione level(GSH)were also analysed.Results:Sodium fluoride treatment significantly decreased gonado-somatic index,sperm count and motility as well as the serum level of luteinizing hormone and testosterone(P<0.05).The histological examination of testes revealed atrophy and degenerative changes in several seminiferous tubules,along with enhanced interstitial space and a reduced number of Leydig cells.There was a highly significant increase in NO and MDA production(P<0.05),while SOD,catalase activities and GSH level decreased significantly(P<0.05).However,C.sinensis significantly restored testicular weight,sperm parameter,hormonal level(P<0.05),and also reversed MDA and NO generation and antioxidant enzymes activities in the testicular tissue(P<0.05).Conclusions:C.sinensis may have an ameliorative role against sodium fluoride-induced oxidative damage in the testis probably because of its antioxidant property.

Preventive effects of β-cryptoxanthin against cadmium-induced oxidative stress in the rat testis

β-cryptoxanthin （CRY）, a major carotenoid of potential interest for health, is obtained naturally from orange vegetables and fruits. A few research studies have reported that CRY could decrease oxidative stress and germ cell apoptosis. The purpose of this study was to examine the effects of CRY on acute cadmium chloride （CdCl2）-induced oxidative damage in rat testes. For this study, 24 rats were divided into four groups, one of which serves as a control group that received intraperitoneal （i.p.） injections of corn oil and physiological saline. The other rats were i.p. injected with CRY （10 μg kg^-1） every 8 h, beginning 8 h before CdCI2 （2.0 mg kg^-1） treatment. The pathological and TUNEL findings revealed that CRY ameliorated the Cd-induced testicular histological changes and germ cell apoptosis in the rats, Furthermore, the Cd-induced decrease in the testicular testosterone （T） level was attenuated after CRY administration （P 〈 0.05）. The administration of CRY significantly reversed the Cd-induced increases in the lipid peroxide （LPO） and malondialdehyde （MDA） levels （P 〈 0.01）. The testicular antioxidants superoxide dismutase （SOD）, catalase （CAT） and glutathione （GSH） were decreased by treatment with Cd alone but were restored by CRY co-treatment. These results demonstrated that the application of CRY can enhance the tolerance of rats to Cd-induced oxidative damage and suggest that it has promised as a pharmacological agent to protect against Cd-induced testicular toxicity.