Article

Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice

Authors:
  • School of Medicine, Shihezi University
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Abstract

To determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity. Sixty male Kunming mice received the following treatments by gavage: normal saline solution (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100 mg/kg); ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1), glutathione S-transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO +GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NQO1, and GST. GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

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... The substantial role of oxidative stress in As-induced toxicities has been evaluated in different studies [10,54]. According to the results reported in several studies, it is assumed that As has the potential to initiate a cascade of events culminating in oxidative stress in the testicular microenvironment [51,55,56]. In our study, we indicated that As significantly induced the overgeneration of ROS in the testicular tissue. ...
... As previously stated, it was observed that treating the mice with As significantly elevated the levels of MDA and protein carbonyl content in the testicular tissue. In accordance with these results, various studies reported that exposure to As commenced lipid peroxidation and induced damage to the protein structures within the mice's testicular tissue [51,53,55,62,63]. Another significant aspect of As male reproductive toxicity is that glutathione level and the activities of antioxidant defense enzymes might be detrimentally affected following the administration of As [51,55,62,64]. ...
... In accordance with these results, various studies reported that exposure to As commenced lipid peroxidation and induced damage to the protein structures within the mice's testicular tissue [51,53,55,62,63]. Another significant aspect of As male reproductive toxicity is that glutathione level and the activities of antioxidant defense enzymes might be detrimentally affected following the administration of As [51,55,62,64]. Correspondingly, the results of our study demonstrated significant decreases in the level of glutathione and a significant reduction in antioxidant enzymes GPx and SOD activities in the group that received arsenic. ...
Article
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Exposure to arsenic is linked to a wide range of diseases, in particular male reproductive toxicities. Trametes versicolor is a traditional medicinal fungus with a remarkable potential for antioxidant activity. The purpose of this study was to examine the ameliorating effects of water and methanol extracts of T. versicolor on arsenic-induced male reproductive toxicities via the abrogation of oxidative stress. The mice were divided as follows: control: normal saline, As: arsenic (15 mg/kg), WE: water extract (400 mg/kg), ME: methanol extract (400 mg/kg), As + WE: arsenic (15 mg/kg) + water extract (100, 200, 400 mg/kg), As + ME: arsenic (15 mg/kg) + methanol extract (100, 200, 400 mg/kg), and positive control: arsenic (15 mg/kg) + vitamin C (500 mg/kg). Animals were treated via the intraperitoneal route. About 24 hr later, the mice were euthanized, and oxidative stress parameters (reactive oxygen species [ROS], lipid peroxidation, glutathione concentration, protein carbonylation, glutathione peroxidase, and superoxide dismutase activity), histopathological changes and sperm parameters (count, motility, and morphology) were examined in the testicular tissue. Arsenic caused significant pathological changes in the testicular tissue and sperm morphology and significantly reduced sperm count and motility. Moreover, arsenic mediated oxidative stress via significant increases in ROS generation, lipid peroxidation, and protein carbonyl content, as well as significant depletion in glutathione concentration and superoxide dismutase and glutathione peroxidase activities. Although, coadministration of water and methanol extracts of T. versicolor at 200 and 400 mg/kg counteracted arsenic-induced oxidative and histopathological damages and improved sperm parameters. Our study indicated that T. versicolor ameliorated arsenic-induced testis toxicity and sperm dysfunction via attenuation of oxidative damage.
... Mitigation of arsenic-induced oxidative stress by GSE resulted in normalization of liver and kidney function and reduced inflammation. The role of GSP on antagonizing arsenicinduced oxidative stress has been investigated in vitro [72,74] and in vivo [74,85]. The treatment of hepatocyte cell line L-02 with GSP mitigates arsenic cytotoxicity by reducing oxidative stress and cell apoptosis [72]. ...
... The effect of GSP on oxidative stress is mediated through Nrf2 judging by increased expression of this molecule and its target genes (HO-1 and NQO1) in cells treated with GSP solely and in combination with arsenic. Besides the liver, protective effects of GSP against oxidative stress induced by arsenic were shown in vitro in human bronchial cells (BEAS-2B cells) [74], in the lungs [74] and testis [85] following 5-week co-treatment of mice with arsenic and GSP. ...
... extract [83,84]; proanthocyanidin [72,74,85] commercial cop.o. 12 mo [83,84] or 5 w [74,85], in vitro [72,74] lungs [74], liver [83], kidney [84], testis [85], BEAS-2B cells [74], L-02 cells [72] GSH [72,74,83], GSSG [83], CAT [74,83], SOD [72,74,83,85], GPx [74,83,85], GR [83], ROS [72,74,83,84], LPO [72,74,[83][84][85], PC [83,84], T-AOC [85], 8-OHDG [85], HO-1 [72,85], GST , NQO1, Nrf2 [72,85] Emblica officinalis: fruits [86][87][88][89][90] water [86], ethyl acetate [87][88][89][90] pre- [86], co- [87][88][89][90] acute i.p. [86]; p.o. 24 d [87]or 30 d [88][89][90] liver [86][87][88], thymus [89], spleen [90] LPO, SOD, CAT [86][87][88][89][90], GST [86,88], GSH [88,89], CD, NPSH [87], GPx [88], ROS [89,90] Trichosanthes dioica: root [91], fruit [92,93] ethanol [91,92], water [93] liver, kidney [106], brain, blood [106,110] GSH [106,110], GSSG [106), SOD, CAT [106,110], GPx [106], LPO [110] Psidium guajava: leaves [99] water co-p.o., 6 w liver, kidney, brain, blood P. granatum [103], I. aquatica [70], M. officinale [71] and garlic [97] reduce arsenic burden in tissues, while O. sanctum [106], T. purpurea [101] and M. officinale [75] have no effect. In addition, although the effect of different corn extracts (water, ethanol, salt and alkali) on the reduction of arsenic-induced oxidative stress was poorly described (authors have measured the GSH level solely), they reduced arsenic burden in various tissues, with aqueous extract being the most effective [107]. ...
Article
Background Heavy metals are elements that are naturally found in the earth. They are used in many modern-day applications, in agriculture, medicine, and industry. Heavy metal poisoning occurs when body’s soft tissues absorb too much of a particular metal. The heavy metals of interest for this review paper were cadmium, arsenic, mercury and lead, since these are the most common metals that the human body can absorb in toxic amounts. Different plant species were investigated in recent years for their effect on oxidative stress parameters after intoxication with heavy metals. Objectives This review paper is focused on current update to research on heavy metals induced oxidative stress in animal models and improvement of the oxidative stress parameters upon/co-/after treatment with different plant extracts and isolated compounds. Results Various parameters of oxidative stress were investigated and their improvement with plant extracts/compounds was noticed in the brain, lungs, kidneys, liver, uterus, testis, thymus, spleen, heart, skin and blood of experimental animals. Common parameters used to determine oxidative stress in animals were: superoxide dismutase; catalase; reduced glutathione; glutathione reductase; glutathione-S-transferase; glutathione peroxidase; lipid peroxidation; oxidized glutathione; malondialdehyde; xanthine oxidase; nonprotein-soluble thiol; thioredoxin reductase; total sulphydryl group; nitric oxide; γ-glutamyl cysteine synthetase. Conclusions The most investigated species for antioxidant effects upon intoxication with heavy metals seem to be Allium sp., Bacopa monniera, Camellia sinensis, Moringa oleifera, Vitis vinifera and Zingiber officinale. According to literature data, the most promising effect to alleviate symptoms of intoxication was achieved with proanthocyanidins obtained from Vitis vinifera.
... Second group (GSPE): Mice were with GSPE (50 mg/kg bw/every 2day/per OS for 2 weeks) [17] and injected with physiological saline solution. ...
... Fourth group (EST and GSPE): Mice were injected subcutaneously with 2.5 million cells of EAC/mouse [18] and treated with GSPE (50 mg/kg bw/every 2day/per OS for 2 weeks) at the same time [17]. ...
... Fifth group (EST then GSPE): Mice were injected subcutaneously with 2.5 million cells of EAC/mouse [18] and left for 2 weeks, after the development of solid tumor, mice were treated with GSPE (50 mg/kg bw/every 2day/per OS) for another 2 weeks [17] 2.5. Sampling 2.5.1. ...
Article
The current study was carried out to evaluate the protective effect of grape seed proanthocyanidins extract (GSPE) against Ehrlich solid tumor (EST) induced renal injury, with the respect to DNA fragmentation and P53 and PCNA proteins expression in renal tissue. A total of 50 female mice were randomly assigned into five groups. Control mice were injected with physiological saline solution. Mice of the 2 nd group were administered with GSPE (50 mg/kg bw/every 2day/per OS) for 2 weeks and injected with physiological saline solution. Mice of the 3 rd group were injected subcutaneously with 2.5 million cells of EAC/mouse. Mice of the 4 th group were injected with EAC as the 3 rd group and administered with GSPE as the 2 nd group simultaneously for 2 weeks. Mice of the 5 th group were injected with EAC as the 3 rd group and left for 2 weeks (till development of solid tumor), then treated with GSPE for another 2 weeks. EST significantly increased serum levels of urea, creatinine, potassium and chloride. In addition, it induced renal tissue and DNA injuries and increased P53, PCNA and ki67 proteins expression in renal tissues. On the other hand, it decreased serum levels of sodium and calcium ions. However, treatment of EST bearing mice with GSPE normalized serum levels of the above-mentioned parameters and improved renal tissue structure and reduced renal tissue DNA damage and P53, PCNA and ki67 proteins expression. These results indicated that GSPE is a promising nephron protective agent against EST induced renal injury.
... Studies have shown that adding an appropriate concentration of GSPs can significantly improve the semen cryopreservation effect of pigs [20,21]. Moreover, a study has shown that GSPs could alleviate oxidative stress in vivo [22], and dietary GSPs could prevent ultravioletradiation-induced non-melanoma skin cancer through the enhanced repair of damaged DNA-dependent activation of immune sensitivity [23]. In addition, in vitro and vivo malformation experiments in mice proved that GSPs do not have potential genotoxicity but have certain anti-mutagenic properties, which can effectively reduce the mitochondrial mutation rate [24]. ...
... The study by Jaime M et al. indicated that the higher the intake of antioxidant nutrients like vitamins C, E, and 3-carotene, the higher the semen quality, including sperm count number and motility in patients attending a fertility clinic [12]. Previous studies also showed that GSPs could mitigate cisplatin and arsenic-induced oxidative stress in research on rodents [22,39]. Especially given the ban on antibiotics as feed additives, phytogenic feed plays an important role in feed additives due to its antioxidant and anti-inflammatory characteristics; this includes ginger, green tea, echinacea extract, purslane extract, honey suzuki, moringa and rosemary, and other phenolic compounds [40,41]. ...
Article
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Oxidative stress leads to a decrease in semen quality during semen cryopreservation and fresh semen production. Grape seed proanthocyanidins (GSPs) are endowed with well-recognized antioxidant, anti-inflammatory, anti-cancer, and anti-aging activities. Therefore, the objective of this experiment was to explore the effects of GSPs on the quality of fresh and cryopreserved semen to provide a basis for GSPs as a new dietary additive and semen diluent additive for males’ reproduction. Fresh semen from three healthy bulls aged 3 to 5 years old were gathered and mixed with semen diluents dissolved with 0 µg/mL, 30 µg/mL, 40 µg/mL, 50 µg/mL, and 60 µg/mL GSPs respectively. The motility, physiological structures (acrosome integrity, membrane integrity, mitochondrial activity), and antioxidant capacity of frozen–thawed sperm were measured after storage in liquid nitrogen for 7 days (d). Bulls were fed with 20 mg/kg body weight (BW) GSPs in their diet for 60 days; the weight of the bull is about 600 kg. Then, the reproductive performance and antioxidant indexes of bulls were measured before and after feeding. The results demonstrated that GSPs supplementation significantly increased sperm motility, physiological structures, GSH-Px, and CAT enzyme activities and significantly decreased MDA content in sperm during semen cryopreservation. The optimal concentration of GSPs was 40 µg/mL (p < 0.05). After 20 mg/kg (body weight) GSP supplementation, sperm motility was significantly heightened (p < 0.05), the sperm deformity rate was significantly reduced (p < 0.05), and antioxidant enzyme activities (such as SOD, CAT, and GSH-Px) were significantly enhanced (p < 0.05), and the production of MDA was significantly suppressed (p < 0.05) in serum compared with that before feeding. In conclusion, these results reveal that a certain concentration of GSPs has a good protective effect on sperm damage caused by semen cryopreservation and the reproductive performance reduction caused by stress in bulls, which may be attributed to the antioxidant function of GSPs. In summary, GSPs are a useful cryoprotective adjuvant and dietary additive for bull sperm quality.
... A well-known symptom of oxidative stress is an imbalance between reactive oxygen species (ROS) that exhibit systemic manifestations in a biological system and their ability to easily detoxify and repair intermediates. Since ROS play a significant role in redox signaling, oxidative stress can disrupt normal mechanisms of cell communication [63]. It is believed that changes in the redox state of a cell are believed to have toxic effects through the production of peroxides and free radicals that are capable of oxidizing biological molecules such as unsaturated lipids, proteins, and DNA [64]. ...
... According to this study, GSPE exerts nephrotoprotective and hepatoprotective effects as an antioxidant on high-dose MP-induced oxidative kidney and liver damage. These results are in agreement with those obtained by Shin et al. [65], Li et al. [63], and Liu et al. [26]. ...
Article
In this study, we investigated the effects of grape seed proanthocyanidin extract (GSPE) against the side effects of high-dose administration of methylprednisolone (MP) in male rats. A total of 32 adult Wistar male albino rats were divided into four groups: (1) control (CON), received standard food only; (2) MP, received standard food + intraperitoneal injection of 60 mg/kg MP on day 7; (3) GSPE, received standard food + 200 mg/kg/day GSPE; and (4) MP + GSPE, received standard food + 200 mg/kg/day of GSPE + intraperitoneal injection of 60 mg/kg MP on day 7. All animals in the GSPE and GSPE + MP groups were treated once a day by oral gavage for 14 consecutive days. The feed intake of rats in the MP and MP + GSPE groups decreased significantly by 24.14% and 13.52%, respectively (p < 0.05). Administration of MP resulted in significant increases in serum concentrations of blood urea nitrogen (p < 0.001), glucose (p < 0.01), alkaline phosphatase, and adrenocorticotropic hormone (p < 0.05). High-dose MP administration significantly reduced catalase (p < 0.001) and glutathione peroxidase (p < 0.05) concentrations in the liver and kidney tissues of rats, while glutathione concentrations were only reduced in liver tissue (p < 0.05). The expression levels of Bcl-2 and TNF-α in liver, kidney, and testicular tissue were significantly increased, while the expression levels of caspase-3 were reduced (p < 0.001). Furthermore, sperm concentration was significantly affected by GSPE in rats induced by high-dose MP, and sperm loss was significantly reduced in MP + GSPE (p < 0.05). These findings suggest that GSPE could be useful as a supplement to alleviate MP-induced toxicity in rats.
... Many recent research studies were done to investigate the possible therapeutic effects of GSE in different pathological conditions (Ali et al., 2015;Kadri et al., 2019;Li et al., 2015;Zhang et al., 2014). Recent literature reported the benefits of GSE against oxidative stress and degenerative diseases including cardiovascular dysfunctions, gastrointestinal distress, neurological disorders, hepatic injuries, neoplastic processes, and carcinogenesis (Abd Eldaim et al., 2021;Ben Youssef et al., 2021;Grohmann et al., 2021;Kadri et al., 2021;Mao et al., 2021;Silvan et al., 2021). ...
... Our results were consistent with Ali et al., who examined the effects of GSE supplementation on the hepatic structural changes caused by oxidative stress induced by toxic liver injury, and they found significant structural and functional improvement(Ali et al., 2015). Also,Zhang et al., and Gang et al., found that the GSE improved the symptoms and histological appearance in arsenicinduced nephrotoxicity and testicular injury respectively, in rats(Li et al., 2015;Zhang et al., 2014). The tissue-protective effects of GSE were also coming in accordance with Ahmad et al., who proved significant functional and histopathological ameliorative effects of the GSE in rat models of rheumatoid arthritis(Ahmad et al., 2013). ...
Article
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In the present study, we investigated the antioxidant effect of grape seed extract (GSE) against chronic immobilization stress‐induced zona fasciculata injury in Wistar male rats. Thirty male rats were divided into three groups: Non‐stress group : rats were not subjected to stress protocol and received distilled water orally for 30 days. Stress group : rats received distilled water orally for 15 consecutive days before the induction of chronic immobilization stress experiment (repeated stress for 15 consecutive days), distilled water was continued along with the constant stress experiment. GSE‐stress group : rats treated with oral GSE (300 mg/kg), administered orally for 15 consecutive days before the induction of chronic immobilization stress experiment (repeated stress for 15 consecutive days), GSE was continued along with the stress exposure. Chronic stress was induced by placing each animal in a restrainer for 2 h daily for 15 consecutive days in both Stress and GSE‐stress groups. The serum corticosterone and adrenal cortex malondialdehyde (MDA) levels were measured as indices of stress. Immunohistochemistry of the inducible nitric oxide synthase (iNOS) as a nitrosative stress marker beside the adrenal cortex's ultrastructure, particularly zona fasciculata, was assessed. Chronic restraint stress significantly elevated the serum corticosterone and adrenal cortex MDA levels, while oral administration of GSE reduced the serum corticosterone level, adrenal cortex MDA levels, and iNOS immunoreactivity in zona fasciculata. Besides, adrenocortical ultrastructure significantly improved. These results suggested that GSE enhanced the antioxidant defense against reactive oxygen species produced under chronic stress conditions, protecting the adrenal cortex. Research Highlights This research highlighted the significant protective effects of grape seed extract administration on the histological findings, both in light and electron microscopic studies, as well as the biochemical and functional parameters in cases of stress‐induced adrenal cortex injury in rats.
... An impaired antioxidant defense mechanism along with OS might be the reason for arsenic-associated toxicity, which might lead to a hostile impact upon reproduction. Earlier, Li et al. (2015) also stated that arsenic trioxide treated mice showed a significantly diminished sperm count, testis somatic index, activity levels of SOD, GSH, and total antioxidative capability than the control group (31). ...
... An impaired antioxidant defense mechanism along with OS might be the reason for arsenic-associated toxicity, which might lead to a hostile impact upon reproduction. Earlier, Li et al. (2015) also stated that arsenic trioxide treated mice showed a significantly diminished sperm count, testis somatic index, activity levels of SOD, GSH, and total antioxidative capability than the control group (31). ...
Research
Arsenic toxicity has become one of the major public health problems in certain parts of the world. Thus, it is rational to find out a suitable compound to prevent arsenic-induced toxicity for clinical usage. Hence, the Coenzyme Q10 and Vitamin E were tested against arsenic-induced testicular oxidative stress and DNA damage. The mice were divided into five groups, animals of the four groups were exposed to 136 ppm arsenic via drinking water for 30 days. Subsequently, animals of three groups were treated with Vitamin E (50 mg/kg b.wt.), Coenzyme Q10 (10 mg/kg b.wt.), and their combination for 30 days, and animals of the 4th group were maintained without antioxidant treatment. The animals of the 5 th group (without any treatment) served as control. Thereafter, blood was collected, for DNA damage study, and testis dissected out to assess oxidative stress. The body and testis weight gain was lower in the arsenic subjected group compared to the control group whereas antioxidants (Vitamin E, Coenzyme Q10, and combination) treatment checks to some extent this decline. Biochemical data indicated that lipid peroxidation level was higher while reduced glutathione, total thiol, superoxide dismutase, and total protein level was significantly lesser in the arsenic exposed group compared to the control group, and antioxidants treatment diminished arsenic-induced these alterations to some extent. Arsenic induces DNA damage in the blood cells of mice by displaying a significantly lower head DNA percentage and a higher level of tail DNA percentage, tail length, tail moment, while Vitamin E, Coenzyme Q10, and combination were able to lower these changes. The data further revealed that the combined treatment of Vitamin E, Coenzyme Q10 is more effective than the treatment of these antioxidants individually.
... Our findings indicated that meaningful elevation in testicular H 2 O 2 and MDA companies with a notable diminution of GSH, SOD, and CAT in As-exposed rats to at 10 mg/kg BW for 4 weeks. These results were consistent with those findings published by Yilmaz et al. (2018) and Li et al. (2015); they reported that male rats showed a noteworthy increase in testicle oxidative stress markers like H 2 O 2 and O − 2 as well as a salient reduction in GSH, SOD, and GPx following exposed to sodium arsenite at 5 mg/kg Bw for 28 days. ...
... Thence these enzymes act as the protector against an extra generation of free radicals. Our findings agreed with many previous studies; these reports explicated that the reduction in SOD and CAT activity in reproductive tissues was an indicator of increased consumption toward normalized H 2 O 2 and MDA formed due to As treatments to rats (Ramanathan et al. 2003;Li et al. 2015;Mahajan et al. 2018). ...
Article
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Arsenic (As) indelibly exists in the environment and may reach to a food chain. Flavors and herbs are recognized sources of natural antioxidants that play imperative against harmful chemical pollutants. Ginger is utilized around the world as a zesty condiment. This study assessed the ability of ginger extract (GE) as a protector to improve regenerative disabilities initiated by sodium arsenate in reproductive functions in male rats. Thirty-two Sprague-Dawley male rats weighted 240 ± 10 g were arbitrarily relegated into four experimental groups (n = 8): the control group; the GE-treated group received at 100 mg/kg BW; the As-treated group received sodium arsenite at 10 mg/kg BW; the fourth group received sodium arsenite additionally GE at mentioned doses for 4 weeks. Phytochemical results of GE revealed that GE had good antioxidative characteristics and high content of total flavonoid, tannins, alkaloids, and total phenolic components. Simultaneously, treatment of GE showed protection against oxidative stress induced by As and restoration of the serum cholesterol, testosterone, LH, and sperm parameter to normal levels. GE significantly improved the antioxidant activities (GSH, SOD, and CAT) as well as H2O2 and MDA in rats received concurrently the GE and As compared with control group. Moreover, the expression of genes controlling the cholesterol transportation and testosterone synthesis (SR-B1, StAR, CYP11A1, 3b-HSD, 17b-HSD, and CYP17a) as well as LHR showed a meaningful improvement in rats treated by GE plus As compared with their expression in the As-treated group. Besides, GE treatment exhibited significant recovered testis histopathological alterations, reduced the arsenic content in testes, and improved the sperm parameters.
... This result suggested that Zingiber officinale Rhizoma may be promising in enhancing sperm healthy parameters. Gang et al. reported that grape seed from Vitis vinifera alleviated arsenic-induced pathological changes and oxidative stress damage in mouse testis [59]. Kunming mice were administered 4 mg/kg arsenic trioxide (ATO) in the morning and grape seed proanthocyanidin extract (100,200, 400 mg/kg) in the evening daily by gavage for 5 weeks. ...
... In the case of ROS, current studies identified the bilateral aspects of ROS in spermatogenesis working as activators as well as inhibitors [173]. Novel mechanisms such as the proliferation of SSC by 5H-purin-6-amine, PI3K/AKR, SFK signaling pathways, and the lack of Nrf2 genes were reported to probably affect arsenic-induced reproductive toxicity [41,59]. Moreover, the fluctuation of hormones such as FSH, are caused by more than one physiological process, therefore the hormonal changes by certain natural products should be interpreted with a wider variety of possibilities [174,175]. ...
Article
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Infertility, a couple's inability to conceive after one year of unprotected regular intercourse, is an important issue in the world. The use of natural products in the treatment of infertility has been considered as a possible alternative to conventional therapies. The present study aimed to investigate the effects and the mechanisms of various natural products on infertility. We collected articles regarding infertility and natural products using the research databases PubMed and Google Scholar. Several natural products possess antioxidant properties and androgenic activities on productive factors and hormones. Antioxidants are the first defense barrier against free radicals produced by oxidative stress (OS). They remove reactive oxygen stress (ROS), reducing insulin resistance, total cholesterol, fat accumulation, and cancer growth. Moreover, various natural products increase endometrial receptivity and fertility ability showing androgenic activities on productive factors and hormones. For example, Angelicakeiskei powder and Astragalus mongholicus extract showed anti-infertility efficacies in males and females, respectively. On the other hand, adverse effects and acute toxicity of natural products were also reported. Tripterygium glycoside decreased fertility ability both in males and females. Results indicate that management of infertility with natural products could be beneficial with further clinical trials to evaluate the safety and effect.
... In terms of reproduction, studies have reported harmful effects of As in the rat testis (Souza et al. 2016). More specifically, exposure of rodents to As results in the suppression of follicle-stimulating hormone and decreases the total proportion of Sertoli cells in the testis (Gang et al. 2015). Despite reports such as this, relatively few data are available regarding the toxic effects of As on male reproductive parameters in domestic animals . ...
... Previous studies have shown that As disrupts the histological structure and male sex hormonal profiles which when combined can lead to altered spermatogenesis . Impaired spermatogenesis in As-treated animals is hypothesized to be due disruption of meiotic and post-meiotic stages of sperms (Gang et al. 2015). In the testes of As-treated Teddy goats, excessive fibroblasts proliferation, indicating necrotic and fibrotic changes in seminiferous tubules and interstitial tissues, was observed. ...
Article
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Arsenic is a major environmental toxicant of concern, affecting both female and male reproductive systems. The present study was conducted to investigate the toxic effects of arsenic on semen quality and reproductive hormones of Teddy bucks, an important domestic species in regions of Pakistan. In addition to arsenic, vitamin C was fed to a subset of animals to determine if there were ameliorative effects on reproductive parameters. Sixteen adult Teddy bucks were randomly divided into four experimental groups: A (control), B (arsenic 5 mg/kg BW/day orally), and C (arsenic 5 mg/kg BW/day plus vitamin C of an oral dose of 200 mg/kg BW/day). The animals in experimental group D were given only vitamin C (oral dose of 200 mg/kg BW/day). Animals were fed treated food once a day for 12 weeks. Semen quality parameters (volume, motility, count, sperm morphology, live dead ratio, sperm membrane integrity, and sperm DNA integrity) of bucks from each experimental group were evaluated on a weekly basis. Hematology and the level of arsenic in the blood were assessed every 2 weeks. Serum was collected fortnightly to measure reproductive and stress hormones (testosterone, luteinizing hormone, follicle-stimulating hormones, and cortisol). At the end of the study, all the animals were slaughtered, and the testes of all the animals were collected and evaluated for histopathology. Semen parameters in arsenic-treated bucks were significantly reduced (p < 0.05) compared with controls. Moreover, the levels of male hormones (testosterone, luteinizing hormone, and follicle-stimulating hormone) were significantly decreased in arsenic-treated animals, while cortisol was significantly increased with arsenic exposure. The histopathological lesions in the testes were present in the form of the loss of germinal epithelium and atrophy of Leydig cells. Supplementation of vitamin C however ameliorated the adverse effects of arsenic on semen quality and hormones. The histopathological lesions were also ameliorated due to vitamin C treatment. This study demonstrates that arsenic can adversely affect reproductive endpoints in Teddy goat bucks and supports the hypothesis that vitamin C is an effective treatment in arsenic-induced toxicosis. This study has high significance for Pakistan, as water contaminated with arsenic is a top health concern and is a recurring issue for both domestic animals and humans.
... Hence it isn't astounding that expanded digestion in light of hyperthyroidism can make hepatic brokenness and oxidative harm hepatic frameworks [15]. Several plant extracts have significant antioxidant activity; one of this is a grape seeds that is rich sources for proanthocyanidins [16][17][18][19]. Proanthocyanidins are consists of many polyphenolic compounds and it have become of high importance because of their biological properties (anti-oxidant, anti-inflammatory and anti-carcinogenic) and their protective effects by reducing mitochondria damage and inhibiting cell apoptosis [20,21]. ...
... G1 : Control group in which mice did not received any treatment. G2 : GSPE; mice received GSPE (50 mg/Kg/day) only for three weeks orally by a stomach tube [17]. G3 : Hyperthyroid; mice received 100 µg/Kg Eltroxin in drinking water for 3 weeks to induce the hyperthyroid state [2]. ...
Article
Objectives: Thyroid hormones control the basal metabolic pace of hepatocytes, and can make oxidative harm hepatic frameworks. The reason for this investigation was to investigate how hyperthyroidism-prompted liver danger, oxidative pressure and apoptosis changes could be alleviated with Grape seed proanthocyanidin extract (GSPE). This investigation assessed some biochemical, histological and immunohistochemical changes in post pubertal hyperthyroidism and its effect on liver capacity and structures. Notwithstanding the enhancing job of Grape seed proanthocyanidin remove (GSPE) supplementation was analyzed. Materials and Methods: Fifty male Swiss albino mice were randomly divided into 5 groups (G1, Control; G2, GSPE; G3, Eltroxin-induced hyperthyroid mice; G4, Post treated hyperthyroid with GSPE; G5, Self-treated hyperthyroid mice). Results: Our results revealed that, a significant increase in serum T3, T4, ALT, AST, ALP, liver MDA, P53 levels, injury and P53 expression in hyperthyroid mice when compared to control and GSPE. In contrast; serum albumin, liver catalase, GSH, SOD and Bcl2 were decrease in hyperthyroid mice. Treatment of hyperthyroid mice with GSPE advantages in improving the adverse effect of hyperthyroidism and moreover the histopathological and P53 expression result approves this finding. Conclusions: GSPE can be used in hyperthyroidism treatment to help propylthiouracil or carbimazole or methimazole therapy.
... Oxidative stress is also related to male infertility through sperm dysfunction caused by an increase of oxygen and oxygen-derived free radicals i.e., ROS [44]. In addition, it has been demonstrated that As and Cd exposition reduces male fertility by peroxidative damage to the plasma membrane [43,47]. In this context, a recent study showed that a dosage of 100/mg/kg BW of GSPE significantly decreased the oxidative stress markers i.e., thiobarbituric acid reactive substance (TBARS), lipid hydroperoxides (LOOH), protein carbonyls (PC), conjugated dienes (CD), and nitric oxide in Cd-induced testes-toxicity rats when administering for 4 weeks [43]. ...
... Authors also found a significant decrease of ROS when the extract was employed alone as a treatment and when it was pre-administrated to Cd-treated rats [43,46]. The supplementation with 400 mg/kg/BW of GSPE showed to block As-induced pathological changes and oxidative damage in rats by significantly reducing MDA and 8-OHdG levels and increasing the T-AOC, GSH and SOD activities [47]. In the same line, dosages of 100 and 300 mg/kg BW of GSPE administered to a high-fat diet fed male Sprague Dawley rats significantly decreased malondialdehyde (MDA) levels and increased the glutathione reduced (GSH); glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities of the testes tissue, thus, ameliorating HFD-induced testicular toxicity [44]. ...
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Over the last decade, proanthocyanidins (PACs) are attracting attention not only from the food industry but also from public health organizations due to their health benefits. It is well-known that grapes are a good source of PACs and for that reason, the industry is also focused on grape by-products identification and bioactivity evaluation. Grape seeds extract (GSPE) is a rich source of PACs, mainly composed of monomeric catechin and epicatechin, gallic acid and polymeric and oligomeric proanthocyanidins. Thus, this review encompasses the state-of-art structure and the most recent evidence about the impact of GSPE on chronic diseases, with a focus on oxidative stress, inflammation and metabolic syndrome (MeS)-related disorders such as obesity, diabetes and cardiovascular risk disease in vivo to offer new perspectives in the field that allow further research. Despite the controversial results, is undeniable that PACs from grape seeds are highly antioxidants, thus, the capacity of GSPE to improve oxidative stress might mediate the inflammation process and the progress of MeS-related pathologies. However, further well-design animal studies with standardized dosages and GSPE composition are necessary to shed light into the cause-effect relationship in a more accurate way to later allow a deeper study of the effect of GSPE in humans.
... Chronic exposure to arsenic has also been associated with oxidative stress (Li et al. 2015). Oxidative stress brings about an increase in the production of oxidizing species or a marked decrease in the potency of endogenous antioxidant defenses, such as glutathione (GSH). ...
... Specifically, arsenic is associated with testicular oxidative stress a common feature of male infertility (Li et al. 2015). It is therefore plausible to opine that the development of potent antioxidant agents may be beneficial in the management of hypo-spermatogenesis (Turner and Lysiak 2008;Yousef and Salama 2009). ...
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The global burden of heavy metal especially mercury, arsenic, lead, and cadmium toxicities remains a significant public health challenge. Developing nations are particularly at high risk and carry the highest burden of this hazard. Chelation therapy has been the mainstay for treatment of heavy metal poisoning where the chelating agent binds metal ions to form complex ring–like structures called “chelates” to enhance their elimination from the body. Metal chelators have some drawbacks such as redistribution of some heavy metals from other tissues to the brain thereby increasing its neurotoxicity, causing loss of essential metals such as copper and zinc as well as some serious adverse effects, e.g., hepatotoxicity. The use of natural antidotes, which are easily available, affordable, and with little or no side effects compared to the classic metal chelators, is the focus of this review and suggested as cheaper options for developing nations in the treatment of heavy metal poisoning.
... Recent investigations of naturally derived polyphenols have shown potential as protective and preventive agents that influence a multitude of physiological processes via various signaling pathways. Dietary polyphenols may provide a promising therapeutic or preventive strategy to mitigate the health risks associated with air pollution, particularly from PM2.5 exposure [33]. For instance, pretreating A549 cells with the antioxidant morin effectively protected against PM2.5-induced toxicity and restored gene expression levels [34]. ...
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PM2.5, a fine particulate matter, poses considerable health risks. When inhaled, PM2.5 can deeply penetrate the lungs, triggering respiratory issues such as pneumonia and bronchitis, aggravating heart and lung conditions, increasing the risk of lung cancer, causing cardiovascular problems, and affecting the nervous, immune, and reproductive systems. This study investigated the protective effects of the combination extract (CRGE) of Thunbergia laurifolia Lindl. (Rang Chuet) water extract (RWE), and Zingiber officinale (ginger) ethanol extract (GEE) against PM2.5-induced oxidative stress in A549 and HepG2 cells. CRGE exhibited superior cytoprotective effects compared to the single extracts (RWE and GEE) by significantly reducing PM2.5-induced cytotoxicity and reactive oxygen species production while enhancing antioxidant enzyme activity. To investigate the effects of PM2.5 exposure on cellular responses, gene expression analysis was conducted on a panel of antioxidant enzymes (heme oxygenase 1, superoxide dismutase, catalase, and glutathione peroxidase), the phase II detoxification enzyme NQO1, and the inflammatory markers interleukin (IL)-6 and IL-8 using the A549 and HepG2 cell lines. CRGE treatment effectively reversed the PM2.5-mediated changes in gene expression in both cell lines, suggesting that it may help restore cellular antioxidant defense mechanisms and mitigate PM2.5-induced oxidative stress. This study showed that CRGE holds promise as a natural antioxidant and cytoprotective agent against PM2.5-induced oxidative stress. Further studies are required to investigate the underlying mechanisms and confirm the efficacy of CRGE in vivo.
... Vineetha et al., (2014) highlighted the protective role of polyphenols found in the apple peel, in case of heart injury produced by the action of arsenic trioxide. The extract of Vitis vinifera seeds, protects the liver (Li et al., 2015) and Viscum album extracts has reduced the elevated plasma levels of liver enzymes and clastogenicity induced by sodium arsenite in rats (Adegboyega & Odunola, 2012). The Zea mays extracts might protect rats from accumulation of arsenic in different tissues and oxidative stress, which is reflected by the increasing the glutathione concentration in those tissues (Chowdhury et al., 2009). ...
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Recent research has shown that the level of heavy metals in the human body is near 700 times higher than that of our ancestors. It is known that heavy metals do not degrade and are not broken-down by microorganisms and the period for their elimination from the body is very long. They can accumulate in the liver, brain, kidneys, muscles, bones, nails and hair. The World Health Organization highlights the risks of neurological, renal, liver, heart and bone diseases caused by heavy metals. The treatment for most heavy metal intoxications is chelating therapy, which can extend over a very long period of time and is quite costly. However, complementary treatments with medicinal plants have proven helpful to remove heavy metals by intensify diuresis, purifying the blood, through their depurative and hepato-protective role, etc. The paper presents the results of some publications in the field, focusing on the plants role in the human body detox.
... Laboratory investigation of the effect of grape seed proanthocyanidin on arsenic-induced reproductive toxicity in male mice showed that administration of the extract improved oxidative stress, Nrf2, and NADPH. This suggests that the extract counteracts arsenic-induced reproductive toxicity by mitigating oxidative damage and inhibiting Nrf2 (Li et al. 2015). ...
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Arsenic is a ubiquitous metalloid and heavy metal that contributes to the global decline in human fertility. Humans are constantly exposed to arsenic through biotic and abiotic sources, especially ingestion of arsenic-contaminated food and water. Its exposure is associated with several adverse health challenges, including reproductive toxicity. In spite of its reported adverse effects, arsenic exposure remains a global challenge. Hence, this study provides a comprehensive review of the literature on the impact and mechanism of arsenic on male and female reproductive function. Additionally, a review of the potential therapeutic strategies is presented. Evidence from the literature reveals that arsenic upregulates reactive oxygen species (ROS) generation which mediates arsenic-induced suppression of the hypothalamic-pituitary–gonadal axis and inactivation of 3β-HSD and 17β-HSD activities, leading to reduced gonadal steroidogenesis. Through several oxidative stress-dependent signaling, arsenic induces the apoptosis of the germ cells, thus contributing to the development of infertility. At the moment, there is no specific treatment for arsenic-induced reproductive toxicity. However, increasing data form the scientific literature reveals the benefits of antioxidants in ameliorating arsenic-induced reproductive toxicity. These molecules suppress ROS generation and maintain optimal activities of the hypothalamic-pituitary–gonadal axis, leading to optimal steroidogenesis and gametogenesis as well as improved germ cells. Overall, this study revealed the impact and associated mechanism of arsenic-induced reproductive toxicity. It also provides evidence from the literature demonstrating potential therapeutic measures in managing arsenic-induced reproductive toxicity.
... Several natural compounds have been identified as active in alleviating arsenic toxicity ( Figure 3, Table 1). Arjunolic acid (4aS,6aR,6aS,6bR,8aR,9R,10R,11R,12aR,14bS)-10,11-dihydroxy-9-(hydroxymethyl)-2,2,6a,6b,9,12ahexamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid These include alpha-lipoic acid (α-LA) and its reduced form dihydrolipoic acid (DHLA) [23,119,120], naringenin [121], epigallocatechin-3-gallate [122][123][124], sulforaphane [125][126][127], allicin [128], eriodictyol [129], hydroxytyrosol [130], lutein [131], oleuropein [132], ellagic acid [133], curcumin [134], biochanin [135], resveratrol [136][137][138], β-Carotene [139], genistein [140], quercetin [141], rutin [142], α-Tocopherol [143,144], and D-pinitol [145], which have shown ameliorative effects against various As-induced toxicities in animal models and in vitro studies. Folic acid supplementation can decrease blood As concentrations [146]. ...
Article
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Chronic exposure to arsenic (As) compounds leads to its accumulation in the body, with skin lesions and cancer being the most typical outcomes. Treating As-induced diseases continues to be challenging as there is no specific, safe, and efficacious therapeutic management. Therapeutic and preventive measures available to combat As toxicity refer to chelation therapy, antioxidant therapy, and the intake of natural dietary compounds. Although chelation therapy is the most commonly used method for detoxifying As, it has several side effects resulting in various toxicities such as hepatotoxicity, neurotoxicity, and other adverse consequences. Drugs of plant origin and natural dietary compounds show efficient and progressive relief from As-mediated toxicity without any particular side effects. These natural compounds have also been found to aid the elimination of As from the body and, therefore, can be more effective than conventional therapeutic agents in ameliorating As toxicity. This review provides an overview of the recently updated knowledge on treating As poisoning through natural dietary compounds. This updated information may serve as a basis for defining novel prophylactic and therapeutic formulations.
... In this study, an increase in HDL-C was found higher in GBTF Group, GBTP Group, GBT Group, and Flaxseed Group than the other groups. Li et al. (2015) mentioned that anthocyanins had an additive effect on HDL-C. Therefore, the rich anthocyanin content of grape seed extract in GBTF Group, GBTP Group, and GBT Group may be responsible for this significant effect in the study. ...
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Detoxification enzymes involved in human metabolism works to minimize the potential xenobiotic-induced damage constantly. Studies have revealed that toxin accumulation plays an important role in the etiology of cardiovascular disease. This study has been designed to provide evidence of medicinal use of bentonite, turmeric (Curcuma longa L.), grape (Vitis vinifera L.) seed, flaxseed (Linum usitatissimum L.), and psyllium (Plantago ovata L.) as detoxification and cholesterol-lowering agents using a hypercholesterolemic model in mice. The potential hypocholesterolemic effects and detoxification ability of these ingredients were evaluated at the same time: Total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, glucose, aspartate aminotransferase, alanine aminotransferase, malondialdehyde, plasma total antioxidant activity, nitric acid, leptin levels and glutathione, glutathione peroxidase, lipid peroxidation, superoxide dismutase and catalase values were measured. It was determined that GBTF group (grape seed extract, bentonite, turmeric, and flaxseed), GBTP group (grape seed extract, bentonite, turmeric, and psyllium), and GBT group (grape seed extract, bentonite, and turmeric) of the tested materials decreased the serum total cholesterol concentration by 64.8, 57.5, and 48.9%, respectively, in mice fed a high cholesterol diet. In addition, it was determined that some detoxification parameters such as superoxide dismutase, catalase, glutathione, and glutathione peroxidase were statistically significantly reversed in GBTF, GBTP, and GBT groups. Flaxseed, psyllium, and bentonite clay did not show significant effects in reducing total cholesterol; however, GBTF, GBTP, and GBT groups interventions had a significant effect in reducing total cholesterol levels. Moreover, it was observed that adding flaxseed or psyllium to the GBT group increased the cholesterol-lowering effect. Therefore, it can be thought that this significant effect is due to the synergistic effect of the raw materials. When the results obtained were evaluated, it was seen that the cholesterol-lowering and detoxification effects of the combinations were higher than from the effect of natural material used alone. As a result, combinations of some of these ingredients have a positive effect on reducing the risk of cardiovascular disease.
... By acting as an antioxidant or free radical scavenger, phytochemicals enhance health [38]. ROS and free radicals are produced when the normal redox status of cells changes, which causes cytotoxicity and damages every component of the cell [39]. Naringin decreases lipid peroxidation and the buildup of ROS [40]. ...
Article
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The application of traditional medicines for the treatment of diseases, including diabetic neuropathy (DN), has received great attention. The aim of this study was to investigate the ameliorative potential of naringin, a flavanone, to treat streptozotocin-induced DN in rat models. After the successful induction of diabetes, DN complications were measured by various behavioral tests after 4 weeks of post-induction of diabetes with or without treatment with naringin. Serum biochemical assays such as fasting blood glucose, HbA1c%, insulin, lipid profile, and oxidative stress parameters were determined. Proinflammatory cytokines such as TNF-α and IL-6, and neuron-specific markers such as BDNF and NGF, were also assessed. In addition, pancreatic and brain tissues were subjected to histopathology to analyze structural alterations. The diabetic rats exhibited increased paw withdrawal frequencies for the acetone drop test and decreased frequencies for the plantar test, hot plate test, and tail flick test. The diabetic rats also showed an altered level of proinflammatory cytokines and oxidative stress parameters, as well as altered levels of proinflammatory cytokines and oxidative stress parameters. Naringin treatment significantly improved these parameters and helped in restoring the normal architecture of the brain and pancreatic tissues. The findings show that naringin’s neuroprotective properties may be linked to its ability to suppress the overactivation of inflammatory molecules and mediators of oxidative stress.
... Lutein treatment at a dose of 40 mg/kg given orally for five weeks increased mRNA expression of Nrf-2 downstream genes (HO-1, GST, and NQO1) in response to As exposure [180]. Proanthocyanidin, grape seed extract, given orally at doses of 100 and 200 mg/kg for 5 weeks, boosted T-AOC, Nrf-2 expression, GSH, and SOD activity, while decreasing MDA and 8-OHdG levels [181]. Green tea component, epigallocatechin-3-gallate (EGCG) at a dose of 20 mg/kg intraperitoneally for 40 days restored sperm kinetic characteristics, structural membrane integrity (SMI), and functional membrane integrity (FMI). ...
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Arsenic (As) is a poisonous metalloid that is toxic to both humans and animals. Drinking water contamination has been linked to the development of cancer (skin, lung, urinary bladder, and liver), as well as other disorders such as diabetes and cardiovascular, gastrointestinal, neurological, and developmental damage. According to epidemiological studies, As contributes to male infertility, sexual dysfunction, poor sperm quality, and developmental consequences such as low birth weight, spontaneous abortion, and small for gestational age (SGA). Arsenic exposure negatively affected male reproductive systems by lowering testicular and accessory organ weights, and sperm counts, increasing sperm abnormalities and causing apoptotic cell death in Leydig and Sertoli cells, which resulted in decreased testosterone synthesis. Furthermore, during male reproductive toxicity, several molecular signalling pathways, such as apoptosis, inflammation, and autophagy are involved. Phytonutrient intervention in arsenic-induced male reproductive toxicity in various species has received a lot of attention over the years. The current review provides an in-depth summary of the available literature on arsenic-induced male toxicity, as well as therapeutic approaches and future directions.
... Several natural compounds have been identified as active in alleviating arsenic toxicity ( Figure 3, Table 1). These include alpha-lipoic acid (α-LA) and its reduced form dihydrolipoic acid (DHLA) [23, 119,120], naringenin [121], epigallocatechin-3-gallate [122][123][124], sulforaphane [125][126][127], allicin [128], eriodictyol [129], hydroxytyrosol [130], lutein [131], oleuropein [132], ellagic acid [133], curcumin [134], biochanin [135], resveratrol [136][137][138], β-Carotene [139], genistein [140], quercetin [141], rutin [142], α-Tocopherol [143,144], and D-pinitol [145], which have shown ameliorative effects against various As-induced toxicities in animal models and in vitro studies. Folic acid supplementation can decrease blood As concentrations [146]. ...
Article
Full-text available
Chronic exposure to arsenic (As) compounds leads to its accumulation in the body, with skin lesions and cancer being the most typical outcomes. Treating As-induced diseases continues to be challenging as there is no specific, safe, and efficacious therapeutic management. Therapeutic and preventive measures available to combat As toxicity refer to chelation therapy, antioxidant therapy, and the intake of natural dietary compounds. Although chelation therapy is the most commonly used method for detoxifying As, it has several side effects resulting in various toxicities such as hepatotoxicity, neurotoxicity, and other adverse consequences. Drugs of plant origin and natural dietary compounds show efficient and progressive relief from As-mediated toxicity without any particular side effects. These natural compounds have also been found to aid the elimination of As from the body and, therefore, can be more effective than conventional therapeutic agents in ameliorating As toxicity. This review provides an overview of the recently updated knowledge on treating As poisoning through natural dietary compounds. This updated information may serve as a basis for defining novel prophylactic and therapeutic formulations.
... 167 Grape seed extracts typically act by alleviating oxidative stress and endoplasmic reticulum stress-induced apoptosis. [168][169][170] Pre-clinical studies of grape seed extracts in animal models of CKD have also reported improved kidney function, decreased proteinuria and reduced podocyte cell death. 171 Clinical trials have demonstrated that grape seed extracts increased GFR, decreased proteinuria and triglycerides, prevented anemia, and counteracted plasma low density lipoprotein and thrombocytopenia. ...
Article
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Chronic kidney disease (CKD) is debilitating, increasing in incidence worldwide, and a financial and social burden on health systems. Kidney failure, the final stage of CKD, is life-threatening if untreated with kidney replacement therapies. Current therapies using commercially-available drugs, such as angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and calcium channel blockers, generally only delay the progression of CKD. This review article focuses on effective alternative therapies to improve the prevention and treatment of CKD, using plants or plant extracts. Three mechanistic processes that are well-documented in CKD pathogenesis are inflammation, fibrosis, and oxidative stress. Many plants and their extracts are already known to ameliorate kidney dysfunction through antioxidant action, with subsequent benefits on inflammation and fibrosis. In vitro and in vivo experiments using plant-based therapies for pre-clinical research demonstrate some robust therapeutic benefits. In the CKD clinic, combination treatments of plant extracts with conventional therapies that are seen as relatively successful currently may confer additive or synergistic renoprotective effects. Therefore, the aim of recent research is to identify, rigorously test pre-clinically and clinically, and avoid any toxic outcomes to obtain optimal therapeutic benefit from medicinal plants. This review may prove to be a filtering tool to researchers into complementary and alternative medicines to find out the current trends of using plant-based therapies for the treatment of kidney diseases, including CKD.
... At present, the research on the defense mechanism of GSPs is mainly limited to its regulation of apoptosis (Liu X. T. et al., 2018), which has been the main cause of GC death and follicular atresia (Tilly et al., 1995 and;Matsuda-Minehata et al., 2006). GSPs relieve the oxidative stress of testicular tissue caused by arsenic and cisplatin in rodents (Genç et al., 2014;Zhao et al., 2014;Li et al., 2015), skeletal muscle of diabetic rats induced by low-dose streptomycin and high-sugar/high-fat (Ding et al., 2013), cyclosporine A poisoning in the heart tissue (Ozkan et al., 2012) and the porcine ovary induced by diquat . Meanwhile, GSPs pretreatment effectively alleviates the apoptosis of porcine GCs induced by oxidative stress in vitro and ovarian aging by increasing antioxidant enzyme activity and the expression of antioxidant genes in aging ovaries . ...
Article
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A significant decrease in poultry egg production occurs due to ovarian aging and autophagy is one of the important factors of ovarian aging that is induced predominantly by oxidative stress. Increasing evidence showed potential roles of plant-derived grape seed proanthocyanidin (GSPs) in protecting ovarian granulosa cells (GCs) from oxidative damage, although the underlying mechanism is still unclear. Here we investigated the possible functions of autophagy involved in the preventive effect of GSPs on oxidative stress in the GCs of ovarian hierarchical follicles of laying chickens. The results showed that increased autophagy was observed in the aging hens (580-day-old, D580) compared with the peak-lay hens (D280). Treatment of GSPs significantly restored the elevated autophagy and decreased viability of cultured D280 chicken GCs that were elicited by hydrogen peroxide. GSPs also suppressed the increased autophagy in the natural aging hens. Similar to the effect of GSPs on GC viability, inhibition of autophagy also showed a protective effect on the decreased viability of GCs under oxidative damage. However, GSPs were not able to provide further protection in GCs that were pretreated with 3-methyladenine (an autophagy inhibitor). In addition to its promoting action on antioxidant capacity, treatment with GSPs increased survival of GCs from autophagy that was caused by oxidative stress through the FoxO1-related pathway. Inhibition of FoxO1 or activation of PI3K-Akt pathway by GSPs increased the confrontation of GCs to oxidative damage and decreased autophagy in GCs. In addition, activation of the SIRT1 signal inhibited the GCs autophagy that was caused by oxidative stress via GSPs-induced deacetylation of FoxO1. These results revealed a new mechanism of GSPs against oxidative stress of GCs via inhibiting FoxO1, which was probably a possible target for alleviating ovarian aging in laying poultry.
... Grape seed extract (GSE) group Mice received GSE (50 mg/kg body weight) orally day by day, for 2 weeks (Li et al. 2015). ...
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This study evaluated the ameliorative potential of grape seed extract (GSE) against Ehrlich solid tumor (EST)–induced hepatic tissue alterations in mice. The control group was infused with physiological saline. The second group received GSE (50 mg/kg day by day orally) for 2 weeks. The third group was subcutaneously injected with 2.5 million of EST cells. The fourth group was injected with EST cells and treated with GSE extract simultaneously. The fifth group was injected with EST cells and kept for 2 weeks until the appearance of a solid tumor, then treated with GSE for 2 weeks. The phytochemical analysis of GSE revealed the presence of total phenols (17.442 mg GAE/g) and total flavonoid (6.687 mg CE/g) with antioxidant activity of 81.506 mg TE/g DPPH. The Ehrlich solid tumor significantly raised the activities of ALT, AST, and ALP; the level of alpha fetoprotein (AFP) in serum; and the protein expressions of hepatic proliferating cell nuclear antigen (PCNA) and tumor suppressor protein (P53), as well as induced DNA damage and pathological alterations in liver tissue. However, it significantly reduced serum albumin and total protein levels. In contrast, the co- or post-treatment of EST-bearing mice with GSE reduced the activities of ALT, AST, and ALP; the level AFP in serum; and hepatic P53 and PCNA protein expressions. In addition, it reduced EST-induced hepatic DNA damage and pathological alterations, while it increased serum albumin and total protein levels. This study suggested that GSE is a potent hepatoprotective agent and both co- and post-treatment of EST-bearing mice with GSE almost had the same effects. Graphical abstract
... At this dose, it is evident that spermatogenesis was not affected, looking at the fertility index and implantation index (Tables 9 and 10). A possible explanation to the above effects of UNCP administration could be due to the high levels of polyphenols and proanthocyanidins, which have protective effects on the testes by activating Nrf2 signalling and prevent ovarian ageing in hens [56][57][58]. ...
Article
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Unsweetened natural cocoa (UNCP) was evaluated for reproductive toxicity in rats. A preliminary genotoxic potential was evaluated by the DNA comet assay test using C57Bl/6 mice. Both therapeutic dose (TD; 900 mg/kg) and high dose (HD; 9000 mg/kg) of UNCP were used. White Wistar rats were used in two experimental groups. The females received UNCP 15 days before crossing with untreated males. The males received UNCP for 48 days before mating with untreated females. Subacute toxicity was observed during a 14-day oral administration of UNCP. Results show that a high tail DNA% was observed with methyl mesylate administration in all tissues analysed. The lowest tail DNA% value was observed in the liver (1.64 ± 0.26) and kidney (1.63 ± 0.30) during UNCP (TD) administration. UNCP did not induce observable physical congenital malformations on the pubs of treated female and male rats, lacks genotoxic potential, and did not adversely affect pregnancy index, pub weights, and survival index, but UNCP exhibited proimplantation potential (p>0.05).
... In addition, grape seed proanthocyanidins extract (GSPE) can improve the nephrotoxicity and DNA damage caused by cisplatin in rats treated with grape seed extract and fish oil (48). Also, GSPE exhibits scavenging of peroxyl and superoxide radicals that can protect the renal tissue against oxidative stress that causes damage to the renal tissue, apoptosis, and fragmentation of DNA (49,50). Furthermore, treatment of Ehrlich solid tumor (EST) induced renal injury in mice with GSPE improved renal tissue structure and reduced renal tissue DNA damage and P53, PCNA and ki67 proteins expression (51). ...
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The current study focused on investigating the renoprotective effects of grape seed oil (GSO) against hexavalent chromium (Cr (VI))-induced nephrotoxicity. A total of 40 male rats were randomly divided into four groups: group I served as the control group, group II received 1000 mg/L potassium dichromate (353.5 mg/L Cr(VI)) in drinking water for 12 weeks, group III received 3.7 g/kg body weight/day GSO orally for 12 weeks, and group IV received GSO together with potassium dichromate for 12 weeks. Cr(VI) significantly increased serum levels of urea, creatinine, potassium and glucose. In addition, Cr(VI) increased MDA levels and induced renal tissue damage and DNA damage. On the other hand, Cr(VI) decreased serum levels of sodium and antioxidant defence system [reduced glutathione (GSH) and catalase (CAT)]. However, treatment with GSO prevented elevation levels of serum urea, creatinine, potassium and glucose. In addition, GSO enhanced sodium level, renal tissue antioxidant defense system due to its curative effect ameliorated particularly oxidative stress, renal tissue and DNA damage. In conclusion, these results demonstrate that GSO is a promising nephroprotective agent against Cr(VI)-induced nephrotoxicity
... Grape seed procyanidin (GSP), which is extracted from French Pinot Noir red grape seeds, has long been recognized to posse myriads of properties, including antioxidant, antiinflammatory, anticarcinogenic, platelet aggregation inhibiting and metal chelating capabilities, etc. GSP is rich source of monomeric phenolic compounds that scavenge hydroxyl and other radicals, such as superoxide radicals (Balu et al., 2005;Wang et al., 2017). Moreover, GSP protects against the neurotoxic effect of ethanol by reducing the crosslinking of cellular proteins and repairing damaged nerve fibers, promoting normal signal transmission between neurons to improve impaired learning and memory (Li et al., 2015). In addition, GSP has been shown to improve symptoms such as irritability, fatigue and hypomnesia (Mao et al., 2015). ...
Article
Aims: Ethanol is a small molecule capable of interacting with numerous targets in the brain, the mechanisms of which are complex and still poorly understood. Studies have revealed that ethanol-induced hippocampal neuronal injury is associated with oxidative stress. Grape seed procyanidin (GSP) is a new type of antioxidant that is believed to scavenge free radicals and be anti-inflammatory. This study evaluated the ability and mechanism by which the GSP improves ethanol-induced hippocampal neuronal injury. Methods: Primary cultures of hippocampal neurons were exposed to ethanol (11, 33 and 66 mM, 1, 4, 8, 12 and 24 h) and the neuroprotective effects of GSP were assessed by evaluating the activity of superoxide dismutase (SOD), the levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) and cell morphology. Results: Our results indicated that GSP prevented ethanol-induced neuronal injury by reducing the levels of MDA and LDH, while increasing the activity of SOD. In addition, GSP increased the number of primary dendrites and total dendritic length per cell. Conclusion: Together with previous findings, these results lend further support to the significance of developing GSP as a therapeutic tool for use in the treatment of alcohol use disorders.
... As high-fat diet consumption didn't change testicular weight and volume it could be suggested that arsenic administration is more potent than this diet on testicular properties. However, acute administration of arsenic couldn't change the testicular weight (22) , but this variable reduced after 5-week arsenic utilization in male mice (23). So, the duration of arsenic exposure is an important reason to produce a testicular weight reduction. ...
Article
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Objective: Obesity is associated with reproductive disorders. Arsenic disrupts male reproduction by direct effects on the male gonads or androgens secretion. So, the present study was conducted to evaluate the toxic effects of chronic concomitant administration of high-fat diet (HF) and arsenic on the reproductive system of the male mouse. Materials and methods: In this experimental study, 72 adult male mice were randomly divided into 6 groups: low-fat diet (LF0), LF+arsenic 25 ppm, LF+arsenic 50ppm, HF0, HF+arsenic 25 ppm and, HF+arsenic 50 ppm. 24 hours after the last experimental day, plasma samples, the cauda of epididymis and testis were prepared and removed for hormonal, sperm count and histopathological assessments. Results: Testis weight and volume increased in HF0 than other groups except for LF0. Plasma LH and testosterone levels decreased in LF50, HF0, HF25, and HF50 compared to LF0. A similar effect was observed in plasma FSH levels of HF0, HF25 and HF50 groups compared with LF0. Plasma level of estradiol increased in LF50 versus to other groups. Testosterone to estradiol ratio and sperm count decreased in all groups compared to LF0. Reduced interstitial cells and large numbers of vacuoles were observed in germinal epithelium of HF0 group, that these changes were more intense in both concentrations of arsenic-treated mice. Conclusion: Present study indicated that chronic exposure to HF and arsenic-induced hypogonadotropic hypogonadism concomitant with sperm count reduction and testicular damage.
... GSPB2 is one of the main components of proanthocyanidin extracts from grape seed and has been shown to be a potent antioxidant and effective scavenger of free radicals [45]. Recent studies have shown that grape seed proanthocyanidin extract (GSPE) alleviates oxidative damage in mouse testis and liver by activating Nrf2 signaling [46,47]. Another study demonstrated that GSPE can reduce high-fat-diet-(HFD-) induced dyslipidemia in mice by attenuating the HFD-induced upregulation of miR-96 expression [48]. ...
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Oxidative stress is a causal factor and key promoter of all kinds of reproductive disorders related to granulosa cell (GC) apoptosis that acts by dysregulating the expression of related genes. Various studies have suggested that grape seed procyanidin B2 (GSPB2) may protect GCs from oxidative injury, though the underlying mechanisms are not fully understood. Therefore, whether the beneficial effects of GSPB2 are associated with microRNAs, which have been suggested to play a critical role in GC apoptosis by regulating the expression of protein-coding genes, was investigated in this study. The results showed that GSPB2 treatment protected GCs from a H 2 O 2 -induced apoptosis, as detected by an MTT assay and TUNEL staining, and increased let-7a expression in GCs. Furthermore, let-7a overexpression markedly increased cell viability and inhibited H 2 O 2 -induced GC apoptosis. Furthermore, the overexpression of let-7a reduced the upregulation of Fas expression in H 2 O 2 -treated GCs at the mRNA and protein levels. Dual-luciferase reporter assay results indicated that let-7a directly targets the Fas 3 ′ -UTR. Furthermore, the overexpression of let-7a enhanced the protective effects of GSPB2 against GC apoptosis induced by H 2 O 2 . These results indicate that GSPB2 inhibits H 2 O 2 -induced apoptosis of GCs, possibly through the upregulation of let-7a.
... The histopathological analysis of testes showed that arsenic has an adverse effect on the seminiferous tubules at the given dose (5mg/kg BW), consequently on the spermatogenesis process as a whole, as some seminiferous tu-bules appeared depleted of cellularity with an edematous interstitial space with few Leydig cells. Arsenic disrupts meiosis and post-meiotic stages of spermatogenesis (Gang et al., 2015). This severe damage, in this study, is consistent with the previous reports, (Li et al., 2012;Jahan et al., 2015;Zubair et al., 2017). ...
... The current study investigated the expression of HO1 and NQO1, two target genes for Nrf2 binding with ARE at their promoter (27,28). The activity of Nrf2 and the expression of antioxidant genes such as NQO1 and HO1 play protective roles against testicular damage and improve semen quality parameters such as number, motility, and morphology (29,30). The current study indicated that the expression level of Nrf2, HO1, and NQO1 decreased in epididymis of cryptorchid mice over time. ...
... Recently, research on the naturally derived polyphenols has escalated to newer heights as protective and preventive therapeutics unveiled their intervention in various physiological processes by activating several signaling pathways. Modulation of PM 2.5 induced pathology, using dietary polyphenolic compounds could reveal a novel therapeutic or preventive approach against the air pollution related health hazards [30,31]. Epigallocatechin-3-gallate has been reported to restrain lung cancer through up regulation of miR210 via reduced ubiquitination, thus stabilization of the pro-angiogenic factor HIF1α [32]. ...
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Heavy metals are well-known environmental pollutants owing to their toxicity, longevity in the atmosphere, and ability to accumulate in the human body via bioaccumulation. The pollution of terrestrial and aquatic ecosystems with toxic heavy metals is a major environmental concern that has consequences for public health. Most heavy metals occur naturally, but a few are derived from anthropogenic sources. Heavy metals are characterized by their high atomic mass and toxicity to living organisms. Most heavy metals cause environmental and atmospheric pollution, and may be lethal to humans. Heavy metals can become strongly toxic by mixing with different environmental elements, such as water, soil, and air, and humans and other living organisms can be exposed to them through the food chain. Plenty of experimental studies were performed to appraise the promising treatment options from natural products. Additionally, nanotechnology based treatment options are being constantly developed. As an emerging field, nanotechnology is making substantial advances in the analysis and removal of heavy metals from complicated matrices. Removal of heavy metal has been accomplished by the use of a variety of nanomaterials, including graphene and its derivatives, magnetic nanoparticles, metal oxide nanoparticles, and carbon nanotubes, to name a few. Using nanotechnology for heavy metal analysis and removal from food and water resources provides many benefits over traditional methods. These advantages include a broad linear range, low detection and quantification limits, a high sensitivity, and high selectivity. Therefore this review aimed to explore the environmental consequences of the heavy metals, toxicity to the human health, as well as novel therapeutics development from the natural resources. Additionally, nanotechnological and nanomedicinal applications to treat heavy metal toxicity are also highlighted in this review.
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Detoxification enzymes involved in human metabolism works to minimize the potential xenobiotic-induced damage constantly. Studies have revealed that toxin accumulation plays an important role in the etiology of cardiovascular disease. This study has been designed to provide evidence of medicinal use of bentonite, turmeric (Curcuma longa L.), grape (Vitis vinifera L.) seed, flaxseed (Linum usitatissimum L.), and psyllium (Plantago ovata L.) as detoxification and cholesterol-lowering agents using a hypercholesterolemic model in mice. The potential hypocholesterolemic effects and detoxification ability of these ingredients were evaluated at the same time: Total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, glucose, aspartate aminotransferase, alanine aminotransferase, malondialdehyde, plasma total antioxidant activity, nitric acid, leptin levels and glutathione, glutathione peroxidase, lipid peroxidation, superoxide dismutase and catalase values were measured. It was determined that GBTF group (grape seed extract, bentonite, turmeric, and flaxseed), GBTP group (grape seed extract, bentonite, turmeric, and psyllium), and GBT group (grape seed extract, bentonite, and turmeric) of the tested materials decreased the serum total cholesterol concentration by 64.8, 57.5, and 48.9%, respectively, in mice fed a high cholesterol diet. In addition, it was determined that some detoxification parameters such as superoxide dismutase, catalase, glutathione, and glutathione peroxidase were statistically significantly reversed in GBTF, GBTP, and GBT groups. Flaxseed, psyllium, and bentonite clay did not show significant effects in reducing total cholesterol; however, GBTF, GBTP, and GBT groups interventions had a significant effect in reducing total cholesterol levels. Moreover, it was observed that adding flaxseed or psyllium to the GBT group increased the cholesterol-lowering effect. Therefore, it can be thought that this significant effect is due to the synergistic effect of the raw materials. When the results obtained were evaluated, it was seen that the cholesterol-lowering and detoxification effects of the combinations were higher than from the effect of natural material used alone. As a result, combinations of some of these ingredients have a positive effect on reducing the risk of cardiovascular disease.
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In vitro and rodent studies have shown that arsenic (As) exposure can deplete glutathione (GSH) and induce oxidative stress. GSH is the primary intracellular antioxidant; it donates an electron to reactive oxygen species producing glutathione disulfide (GSSG). Cysteine (Cys) and cystine (CySS) are the predominant thiol/disulfide redox couple found in human plasma. Arsenic, GSH, and Cys are linked in several ways. First, GSH is synthesized via the transulfuration pathway and Cys is the rate limiting substrate. Second, intermediates of the methionine cycle regulate both the transulfuration pathway and As methylation. Third, GSH serves as the electron donor for reduction of arsenate to arsenite. Fourth, As has a high affinity for sulfhydryl groups and therefore binds to GSH and Cys. To test the hypotheses that As exposure is associated with decreases in GSH and Cys and increases in GSSG and CySS, i.e., a more oxidized environment. For this cross-sectional study, the Folate and Oxidative Stress Study, we recruited a total of 378 participants from each of 5 water As categories: <10 (n=76), 10-100 (n=104), 101-200 (n=86), 201-300 (n=67), and >300 µg/L (n=45). Concentrations of GSH, GSSG, Cys, and CySS were measured using HPLC. An interquartile range (IQR) increase in water As was negatively associated with blood GSH (mean change = -25.4 µmol/L; 95% CI: -45.3, -5.31) and plasma CySS (mean change = -3.00 µmol/L; 95% CI: -4.61, -1.40). Similar associations were observed with urine and blood As. There were no significant associations between As exposure and blood GSSG or plasma Cys. The observed associations are consistent with the hypothesis that As may influence concentrations of GSH and other non-protein sulfhydryls through binding and irreversible loss in bile and/or possibly in urine.
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Natural dietary antioxidants are studied for their ability to protect cells from miscellaneous damage. Grape seed extract (Vitis vinifera L., Vitacease) is a potent antioxidant. The present study aimed to investigate the protective effect of grape seed extract (GSE) against the possible testicular dysfunction caused by aluminium chloride (AlCl3) in male rats. Twenty sexually mature male albino rats were divided into four equal groups, the first served as negative control, the second received AlCl3 (20 mg/kg bw, 1/ 20 LD 50), the third administered GSE (75 mg/kg bw), and the fourth received AlCl3 and treated with GSE. Doses were given once daily via gavage for 70 consecutive days. The results revealed that, AlCl3 induced significant decrease in final body weight, sex organs relative weight, sperm concentration, motility and viability, serum testosterone concentration and superoxide dismutase (SOD) activity, with significant increase in sperm abnormalities and thiobarbituric acid reactive substance (TBARS) concentrations. Moreover, AlCl3 induced apparent alteration in the histological structure of the testis. Treatment with GSE ameliorated the harmful effects of AlCl3, this was also proved histopathologically by the noticeable improvement in the testis tissues. It may be concluded that GSE may be promising as a natural therapeutic agent in AlCl3-induced reproductive toxicity and oxidative stress in the male rat testes. Hala, A.
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Different forms of aluminium (Al) are environmental xenobiotics that induce free radical-mediated cytotoxicity and reproductive toxicity. Propolis has been reported to be important antioxidant. Therefore, this study aimed at elucidating the protective effects of propolis against reproductive toxicity of aluminium chloride (AlCl3) in male rats. The first group served as control. Group 2 received 34 mg AlCl3/kg bw (1/25 LD50). Group 3 was administered 50 mg propolis/kg bw/day. Group 4 was treated with AlCl3 plus propolis. Treatment was continued for 70 days. AlCl3 caused a decrease in testes, seminal vesicle and epididymis weights, sperm concentration, motility, testosterone level and the activities of 17-ketosteroid reductase, CAT and GST, and GSH content. While, dead and abnormal sperm and testes TBARS concentrations were increased. In the AlCl3-treated group, histopathologic examinations revealed apparent alterations in the testes, where it induced marked lesions in seminiferous tubules. Propolis alone decreased dead and abnormal sperm and TBARS, and increased testosterone, GSH, 17-ketosteroid reductase, CAT and GST. Results showed that propolis antagonized the harmful effects of AlCl3. This was proved histopathologically by the great improvement in testes. In conclusion propolis could be effective in the protection against the reproductive toxicity of AlCl3.
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