Figure - available from: Biological Trace Element Research
This content is subject to copyright. Terms and conditions apply.
Protective effects of ZnONPs on aluminum chloride (AlCl3)-induced inflammation in testis of rats. Data are expressed as mean ± SD values (n = 7). ap < 0.05 vs. the control group; bp < 0.05 vs. the AlCl3-intoxicated group, using the Tukey’s post hoc test
Source publication
Reproductive toxicity is a major challenge associated with aluminum (Al) exposure. Therefore, this study aimed to investigate the effects of zinc oxide nanoparticle (ZnONP) treatment on Al-induced reproductive toxicity in rats. Thirty-two adult male albino rats were allocated into four equal groups as follows: control, AlCl3 orally administered gro...
Citations
... In this study, the increase in serum and testes MDA levels following exposure to AlCl3 can be attributed to an increased burden of oxidative stress. This is likely due to the production of reactive oxygen species (ROS), which in turn induce lipid and protein oxidation, as previously mentioned by recent studies [27][28][29]. Additionally, there was a reduction in TAC activity and sperm count. ...
... The results of this study demonstrated that the administration of AlCl3 (AlCl3) led to a significant reduction in the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. This is in line with prior studies which also observed that AlCl₃ substantially lowered the concentrations of LH, FSH, and testosterone in rat blood [11,29,34]. These studies suggest that AlCl3 acts as an endocrine disruptor, interfering with the synthesis and regulation of various hormones, including testosterone, FSH, and LH. ...
Background: There is a growing focus on aluminum compounds due to their significant impact on fertility, and reproduction. Natural products offer a promising solution for treating heavy metal toxicity as they are effective, have fewer side effects, and are relatively affordable. Objective: This study aimed to investigate the effects of Salvia sahendica hydroalcoholic extract on reproductive toxicity induced by aluminum (Al) exposure in rats. Methods: Thirty-two adult male Wistar rats were divided into four groups: control, AlCl3 orally administered group (40 mg/kg bw), S. sahendica hydroalcoholic extract gavaged group (100 mg/kg bw), and AlCl3+ S. sahendica treated group. The rats were treated daily for 70 consecutive days. Results: Oral administration of AlCl3 resulted in oxidative damage, indicated by an increase in malondialdehyde level and a decrease in total antioxidant content. Additionally, AlCl3-intoxicated rats exhibited significant declines in serum levels of male reproductive hormones testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). However, daily administration of S. sahendica to rats before AlCl3 was found to reduce testicular oxidative stress and improve reproductive markers in the serum, ameliorating the reproductive toxicity induced by Al administration. Conclusion: These findings suggest that S. sahendica could potentially be used as an alternative agent to minimize reproductive toxicity associated with Al exposure.
... Reagents and conditions: (a) TESÀ Cl (20 equiv), imidazole (12 equiv), dry DMF, 0°C to rt over 6 h; (b) RedÀ Al, dry THF, À 10°C, 20 min; (c) a m-benzoic acid analog (4) (8 equiv), DIC (8 equiv), DMAP (8 equiv), CH 2 Cl 2 , rt, 2-5 days; (d) HF/pyridine, pyridine/ AcCN, 0°C to rt, overnight; (e) acetic, propanoic, or cyclopropane carboxylic anhydride (10 equiv), CeCl 3 · 7H 2 O (0.1 equiv), THF, rt, 20 h; (f) TESÀ Cl (3 equiv), imidazole (4 equiv), dry DMF, 0°C to rt, over 45 min; (g) LiHMDS (1.5 equiv), dry THF, À 40°C, 2 h; (h) HF/pyridine, pyridine/AcCN, 0°C to rt, overnight. metal hydride reduction reagent stimulates an undesired intramolecular rearrangement where the newly made C2 alkoxide intermediate ring-opens the adjacent oxetane ring and creates a new furano-taxane (14) (Scheme 2B). [8][9][10] RedÀ Al can also cleave the C4 acyl group to afford an undesired triol (15) in quantitative yield (Scheme 2C). ...
... [11][12][13] Furthermore, the aluminum salts produced in this reaction are considered toxic disposal agents and can cause conjunctivitis and fetal damage. [14][15] Biocatalysis continues to emerge as a promising technology for the assembly of fine chemicals. [16][17][18][19][20] This study uses a taxane benzoyltransferase (mTBT) instead of RedÀ Al to biocatalytically and regioselectively debenzoylate- (22)(23)(24) and rearoylate (26)(27)(28) the C2 hydroxyl of 13-oxobaccatin III scaffolds (without silyl ether protection) (Scheme 3). ...
A taxane 2‐O‐benzoyltransferase (mTBT, derived from Accession: AF297618) biocatalyzed the dearoylation and rearoylation of next‐generation taxane precursors of drugs effective against multidrug‐resistant cancer cells. Various taxanes bearing an acyl, hydroxyl, or oxo group at C13 were screened to assess their turnover by mTBT catalysis. The 13‐oxotaxanes were the most productive, where 2‐O‐debenzoylation of 13‐oxobaccatin III was turned over faster compared to 13‐oxo‐10‐O‐(n‐propanoyl)‐10‐O‐deacetylbaccatin III and 13‐oxo‐10‐O‐(cyclopropane carbonyl)‐10‐O‐deacetylbaccatin III, yielding ~20 mg of each. mTBT catalysis was likely affected by an intramolecular hydrogen bond with the C13−hydroxyl. Oxidation to the 13‐oxo recovered catalysis. The experimental data for the debenzoylation reaction was supported by Gaussian‐accelerated molecular dynamics simulations that evaluated the conformational changes caused by different functional groups at C13 of the substrate. These findings also helped postulate where the 2‐O‐benzoylation reaction occurs on the paclitaxel pathway in nature. mTBT rearoylated the debenzoylated 13‐oxobaccatin III acceptors fastest with a non‐natural 3‐fluorobenzoyl CoA among the other aroyl CoA thioesters evaluated, yielding ~10 mg of each with excellent regioselectivity at laboratory scale. Reducing the 13‐oxo group to a hydroxyl yielded key modified baccatin III precursors (~10 mg at laboratory scale) of new‐generation taxoids.
... Taken together, it can be concluded that Sn levels in plasma might be response for the development of PCOS. Aluminum toxicity resulted severe imbalance of the oxidative-antioxidant system to produce highly reactive oxygen species (ROS), which would damage nucleic acids, lipids and proteins [60]. Other studies investigated that daily systemic aluminum over-expose in women was greater than 100-fold above the typical human daily Al consumption equivalent (0.1 µg/kg) [61]. ...
The objective of this study is to explore the correlation of metal levels with assisted reproductive technology (ART) outcomes in polycystic ovary syndrome (PCOS) patients. The individuals were recruited who met the research criteria, only tubal factor or male infertility served as the control group (n = 40) and patient group was PCOS patients (n = 35). Individuals (n = 75) were divided into PCOS group (n = 35) and control group (n = 40). The normal body mass index (BMI) group (control) includes women with BMI < 25 kg/m² in PCOS group (n = 24) and control group (n = 33), and BMI ≥ 25 kg/m² in PCOS group (n = 11) and control group (n = 7). We performed an analysis of insulin resistance (IR) (n = 15) group and without insulin resistance (NIR) group (n = 20) in PCOS patient and control patients. Comparing difference demographic data, ART outcomes and the metal levels in every group respectively, the correlation of metal levels and ART outcomes in control participants and PCOS patients were analyzed by the Spearman correlation analysis, and multiple linear regression model was used to examine the association between the concentration of 19 metals and ART outcomes in PCOS group and control group. Plasma manganese (Mn), titanium (Ti), sodium (Na), magnesium (Mg), copper (Cu), calcium (Ca)/Mg ratio, and Cu/zinc (Zn) ratio levels in PCOS patients were higher than that in control, while Zn and Ca levels were lower in PCOS patients than that in control. The Mg levels had a positive connection with the number of eggs recovered, and the iron (Fe) levels were positively associated with the number of transplanted embryos in PCOS-IR. In PCOS-NIR, Mn levels positively correlated with the number of follicles and the number of good embryos. Silver (Ag) levels were negatively correlated with the number of follicles, and aluminum (Al) levels were negatively related with the normal fertilization and the number of good embryos. The Spearman analysis in PCOS-BMI ≥ 25 group exhibited that nickel (Ni) levels were negatively associated with the number of follicles. The plasma metal levels seem to affect the clinical manifestations and in vitro fertilization outcomes in assisted reproduction.
... The impact of CYP11A1, HSD-3b, and StAR transcript levels was down-regulated in testicular tissues following the AlCl 3 administration. However, experimental mice exposed to AlCl3 have altered testicular development and testosterone synthesis (Lokman et al., 2022). The injurious effects provoked by the AlCl3 may be attributed to the increased mitochondrial oxidative stress and disorders of the mitochondrial energy metabolism. ...
The male reproductive system is negatively influenced by Al exposure. Al represented a considerable hazard to men’s reproduction capabilities. Amygdalin (AMG) and spirulina platensis (SP) have been considered to have a strong antioxidant and repro-protective activity; also, targeted drug delivery systems called niosomes improve the distribution of water-soluble medications like amygdalin and spirulina. Current study targeted to determine the effectiveness of AMG and SP against negative reproductive impact resulted by aluminum chloride (AlCl3) toxicity. Sixty adult male albino rats were separated into 6 groups, including the control group, which received distilled water; AlCl3 group, which received AlCl3; AMG+AlCl3 group, which received AlCl3+AMG; AMGLN+AlCl3 group, which received AlCl3+amygdalin-loaded niosomes; SP+AlCl3 group, which received AlCl3+SP; and SPLN+AlCl3 group, which received AlCl3+spirulina-loaded niosomes. All treatments were orally gavaged daily for 5 weeks, and rats were weighed weekly. At the termination of the experiment, some males (three from each group) were used for fertility traits via mating thirty virgin rat females (in a ratio of 1:2 and 2:3 male:female, respectively) followed by recording of birth weights and litter size (number of pups per each female) at birth to assess males’ reproductive capability. Other males were euthanized for collection of serum, epididymal semen samples, and tissue samples for biochemical, sperm evaluation, gene expression, and histopathological measurements. There are a considerable number of negative impacts of AlCl3 on male fertility clarified by declined serum testosterone levels; an increased oxidative stress (MDA, TAC); deteriorated semen quality; down-regulation of CYP11A1, StAR, and HSD-3b gene expressions; and testicular tissue degenerative changes. In addition, litter size (number of pups per each female) and birth weights of pups obtained from mated females were affected. AMG and SP treatments, either in niosomal or conventional form, alleviated the AlCl3 negative effects by reducing oxidative stress; increasing testosterone levels; improving semen quality; upregulating of CYP11A1, StAR, and HSD-3b gene expressions; and reducing degenerative changes of testicular tissue. Besides, negative reproductive effect was diminished as observed by changes in the litter size (number of pups per each female) and birth weights of pups obtained from mated females. AMG and SP treatments (either in niosomal or conventional form), ameliorated the AlCl3 negative effects as they possess powerful antioxidant activity, as well as they have the ability to improve the reproductive activity of affected males.
Graphical abstract
... Similar to our findings, ZnO-NPs were found to be efficient in decreasing MDA and increasing reduced glutathione in diabetic rats' testes [31]. Moreover, treating rats with ZnO-NPs for 6 weeks succeeded to defend against aluminum (Al)-induced oxidative stress in the testes [32]. On the other side, Ziamajidi et al. [33] showed that ZnO-NPs at 200 mg/kg induced oxidative stress in the testes. ...
... All histopathological Zn deficiency has been linked to a malfunction in the normal development of Leydig cells as well as impairment in LH receptors, both of which have a negative impact on testosterone biosynthesis [40]. In addition, the favorable effects of cZnO and ZnO-NPs on testosterone and sperm quality may potentially be attributable to their antioxidant activity, which protects testicular tissues from BPA-induced oxidative damage [32], which confirmed our findings. More notably, ZnO-NPs outperformed cZnO in terms of testosterone production, which could be attributed to ZnO-NPs' stronger antioxidant activity than the conventional version [20]. ...
... Zn was a promising treatment to protect thyroid gland against potassium dichromate thyrotoxicity [45]. Additionally, the beneficial effects on thyroid hormones may be due to the high antioxidant activity of cZnO or ZnO-NPs [32], which may protect the thyroid tissue from oxidative damage. ...
Bisphenol A (BPA) is a widely used endocrine disruptor that represents a significant risk to male reproductive function. Zinc (Zn) is vital for appropriate development of testes and to guarantee optimal testicular function and spermatogenesis. Our goal was to investigate if zinc oxide (ZnO), either in conventional or nanoformulation, could safeguard adult male rats’ reproductive performance against the damaging effects of BPA. Signaling expression of CYP11A1 and Nrf-2 in the testis, testicular oxidant-antioxidant status, Bax/Bcl-2 apoptotic ratio, and histological examination of various reproductive organs were all evaluated. Twenty-eight adult male albino rats were divided randomly into 4 groups (7 animals each) including the control, BPA, conventional zinc oxide (cZnO) + BPA, and zinc oxide nanoparticles (ZnO-NPs) + BPA groups. The study was extended for 2 successive months. Our findings revealed strong negative effects of BPA on sperm cell characteristics such as sperm motility, viability, concentration and abnormalities. Additionally, BPA reduced serum levels of testosterone, triiodothyronine (T3), and thyroxine (T4). Also, it evoked marked oxidative stress in the testes; elevating malondialdehyde (MDA) and reducing total antioxidant capacity (TAC). BPA significantly downregulated testicular mRNA relative expression levels of CYP11A1 and Nrf-2, compared to control. Testicular apoptosis was also prompted by increasing Bax/ Bcl-2 ratio in testicular tissue. Histopathological findings in the testes, epididymis, prostate gland, and seminal vesicle confirmed the detrimental effects of BPA. Interestingly, cZnO and ZnO-NPs significantly alleviated all negative effects of BPA, but ZnO-NPs performed better. In conclusion, our findings point to ZnO, specifically ZnO-NPs, as a viable treatment for BPA-induced testicular dysfunction.
... One of the main problems is the adverse side effects promoted by these compounds (Levy et al. 2008;Forzán et al. 2014;Ibrahim et al., 2016b). In this context, the development of new biotechnological approaches is urgent, and many researchers are considering the use of nanoparticles to promote animal sterility safely (Asri-Rezaei et al., 2018;de Brito et al., 2020;Ding et al., 2021;Gavas et al., 2021;Hozyen et al., 2020;Iftikhar et al., 2021;Jivago et al., 2021;Lokman et al., 2022;Morrow et al., 2007). ...
This study aimed to evaluate the gold nanoparticles (AuNPs) animal sterilizing potential after intratesticular injections and long-term adverse reproductive and systemic effects. Adult male Wistar rats were divided into control and gold nanoparticle (AuNPs) groups. The rats received 200µL of saline or AuNPs solution (16µg/mL) on experimental days 1 and 7 (ED1 and ED7). After 150 days, the testicular blood flow was measured, and the rats were mated with females. After mating, male animals were euthanized for histological, cellular, and molecular evaluations. The female fertility indices and fetal development were also recorded. The results indicated increased blood flow in the testes of treated animals. Testes from treated rats had histological abnormalities, shorter seminiferous epithelia, and oxidative stress. Although the sperm concentration was lower in the AuNP-treated rats, there were no alterations in sperm morphology. Animals exposed to AuNPs had decreased male fertility indices, and their offspring had lighter and less efficient placentas. Additionally, the anogenital distance was longer in female fetuses. There were no changes in the histology of the kidney and liver, the lipid profile, and the serum levels of LH, testosterone, AST, ALT, ALP, albumin, and creatinine. The primary systemic effect was an increase in MDA levels in the liver and kidney, with only the liver experiencing an increase in CAT activity. In conclusion, AuNPs have a long-term impact on reproduction with very slight alterations in animal health. The development of reproductive biotechnologies that eliminate germ cells or treat local cancers can benefit from using AuNPs.
... Reproductive toxicity is a major challenge associated with AL exposure. High concentrations of this metal cause the degeneration of the seminiferous tubules, the presence of edema in the testicular intertubular areas, the presence of immature spermatocytes in the lumen, and a decrease in the level of serum testosterone [5]. It has been reported that histopathological findings increase and antioxidant enzymes decrease with AL exposure [6,7]. ...
... This result was consistent with other studies reporting AL-induced reductions in serum testosterone [7,27,28,31]. It is thought that this decrease in serum testosterone levels may be caused by the reduction of gonadotropin secretion from the pituitary gland by blocking calcium channels of AL [5,32]. In addition, a study reported that AL caused testicular dysfunction by inhibiting gonadotropin receptor expression in rats [3]. ...
... AL leads to an increase in germ cell apoptosis and a decrease in the level of intercellular ATP, reducing sperm count and motility [7,36]. Studies have shown that AL administration increases the proapoptotic CASP3 level and cell death in testicular tissue [5,7]. In this current study, it was observed that AL exposure increased proapoptotic BAX and CASP3 levels. ...
Aluminum (AL) is a heavy metal known to have toxic effects on the reproductive system. It is known that N-acetylcysteine (NAC), which has an antioxidant effect, is a useful chelator for heavy metals. This study aimed to determine whether NAC may reduce AL-induced oxidative stress, inflammation, and germ cell apoptosis in testicular tissues and its effects on meteorin-like (METRNL) levels, which are known to play a role in energy metabolism. In this experimental study, 28 Sprague–Dawley male rats were randomly divided into 4 groups (n = 7): control, AL (30 mg/kg/day AL), AL + NAC (30 mg/kg/day AL + 150 mg/kg/day NAC), and NAC (150 mg/kg/day NAC). All AL and NAC applications were performed intraperitoneally for 14 days. At the end of the experiment, the effects of AL and/or NAC applications on testicular tissue were examined histomorphometrically, histopathologically, immunohistochemically, and biochemically. It was determined that AL exposure caused histomorphometric and histopathological changes, oxidative stress, apoptosis of germ cells, and inflammation in testicular tissues. In addition, AL caused an increase in METRNL levels. It was determined that NAC treatment significantly reduced the negative effects of AL. NAC therapy may be a protective strategy in reproductive toxicity due to AL exposure.
... AlCl 3 -induced toxicity in the epididymis, vas deferens, seminal vesicle, and ventral prostate of mice was also reported by ALMurshidi et al. (2021). Moreover, exposure to AlCl 3 has been reported to affect testicular development and testosterone synthesis in experimental animals (Lokman et al. 2021). Xu et al. (2017) found that AlCl 3 exposure promotes mitochondrial oxidative stress, which may contribute to mitochondrial energy metabolism disorder and liver dysfunction. ...
Aluminum, the third most plentiful metal in the Earth’s crust, has potential for human exposure and harm. Oxidative stress plays an essential role in producing male infertility by inducing defects in sperm functions. We aimed to investigate the role of endoplasmic reticulum (ER) stress and mitochondrial injury in the pathogenesis of aluminum chloride (AlCl 3 )-induced testicular and epididymal damage at the histological, biochemical, and molecular levels, and to assess the potential protective role of taurine. Forty-eight adult male albino rats were separated into four groups (12 in each): negative control, positive control, AlCl 3 , and AlCl 3 plus taurine groups. Testes and epididymis were dissected. Histological and immunohistochemical (Bax and vimentin) studies were carried out. Gene expression of vimentin , PCNA , CHOP , Bcl-2 , Bax , and XBP1 were investigated via quantitative real-time polymerase chain reaction (qRT-PCR), besides estimation of malondialdehyde (MDA) and total antioxidant capacity (TAC). Light and electron microscopic examinations of the testes and epididymis revealed pathological changes emphasizing both mitochondrial injury and ER stress in the AlCl 3 group. Taurine-treated rats showed a noticeable improvement in the testicular and epididymal ultrastructure. Moreover, they exhibited increased gene expression of vimentin , Bcl-2 , and PNCA accompanied by decreased CHOP , Bax , and XBP1 gene expression. In conclusion, male reproductive impairment is a significant hazard associated with AlCl 3 exposure. Both ER stress and mitochondrial impairment are critical mechanisms of the deterioration in the testes and epididymis induced by AlCl 3 , but taurine can amend this.
