Article

ROLE OF OXIDATIVE STRESS AND VITAMIN C, E ON MALE FERTILITY: MINI REVIEW

Authors:
  • Govt Medical College Shivpuri MP
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Abstract

Exposure to reactive oxygen intermediates or free radicals cause oxidative stress. These free radicals cause damage to proteins, nucleic acids and cell membranes. Increasing evidence suggests that the cumulative damage caused by reactive oxygen species contribute to numerous diseases. Recently many stressful conditions reported to disturb the prooxidant and antioxidant balance of the cells by generating reactive oxygen species and oxygen free radicals thereby inducing oxidative stress. Accumulating evidence has implied that the production of free radical plays a critical role in male reproduction and many studies reported that stress play important role in etiology of male infertility. Chronic psychological and physical stresses induce erectile dysfunction, possibly resulting from neurotransmission changes in various erectile response pathways and a reduced blood flow in male genital organs. Due to high PUFAs content in sperm plasma membrane which results vulnerable to oxidative stress, low membrane fluidity and loss of sperm oocyte interaction. After molecular biology, pharmacology and therapeutics became active for finding the molecules for quenching free radicals. The recent growth in the knowledge of free radicals or ROS is producing a medical revolution and that promises a new age of health disease management. Supplementation of antioxidants improve the sperm quality and reduces oxidative stress induced infertility.

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... A study that examined the effect of Vitamin D on sperm motility confirmed a positive relationship between both serum and seminal plasma with the level of Vitamin D, and the reason for that may be due To the concentration of vitamin D in the seminal plasma, which stimulates the sperm mitochondria to produce ATP during the electron transport chain by activating the cAMP / PKA pathway while increasing the intracellular calcium ion (25). Vitamin C, which plays an active role in protecting the sperm formation process while maintaining semen integrity by increasing testosterone concentration while preventing sperm agglutination through its effective role as an antioxidant that fights free radicals (26). Vitamin E is also one of the most important vitamins and anti-sterility by protecting the cellular membranes of the sperm that are rich in polyunsaturated lipids from oxidative stress and thus inhibiting fatty oxidation which enhances spermatogenesis by increasing the fluidity of sperm membranes while reducing the production of abnormal sperm (26). ...
... Vitamin C, which plays an active role in protecting the sperm formation process while maintaining semen integrity by increasing testosterone concentration while preventing sperm agglutination through its effective role as an antioxidant that fights free radicals (26). Vitamin E is also one of the most important vitamins and anti-sterility by protecting the cellular membranes of the sperm that are rich in polyunsaturated lipids from oxidative stress and thus inhibiting fatty oxidation which enhances spermatogenesis by increasing the fluidity of sperm membranes while reducing the production of abnormal sperm (26). The results also showed a high concentration of testosterone in the walnut group, possibly due to compounds in the Walnut such as arginine and aspartic acid, and niacin, which has a role in the production of steroid hormones (27). ...
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Oxidative stress contributes to defective spermatogenesis leading to male factor infertility. The aim of this study was to review the current literature on the effects of various antioxidants to improve fertilisation and pregnancy rates. The sources of literature were Pubmed and the Cochrane data base. Reviewing the current literature revealed that Carnitines and vitamin C and E have been clearly shown to be effective by many well-conducted studies and may be considered as a first line treatment. The efficacy of antioxidants, such as glutathione, selenium and coenzyme Q10 has been demonstrated by few, but well-performed studies, and may be considered second line treatment. There is, however, a need for further investigation with randomised controlled studies to confirm the efficacy and safety of antioxidant supplementation in the medical treatment of idiopathic male infertility as well as the need to determine the ideal dose of each compound to improve semen parameters, fertilisation rates and pregnancy outcomes.
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To study the anti-inflammatory mechanisms of total glycosides of Acanthopanax Giraldii (TGA). The changes of prostaglandin E(2)(PGE(2)), tumor necrosis factor (TNF-alpha), nitric oxide (NO), and expressions of COX-1 mRNA and COX-2 mRNA in BALB/c mouse macrophages were observed by the radioimmunoassay, ELISA and nitric acid reduction and RT-PCR in the presence or absence of TGA. (1) TGA could significantly decrease the production of PGE(2)and NO in mouse peritoneal macrophages. The inhibitory rate to LPS-induced PGE(2)production was 87% (TGA 100 mg/L, P<0.05, vs. LPS) and 62% (TGA 20 mg/L, P<0.05, vs. LPS), respectively. The inhibitory rate of NO production in mouse peritoneal macrophages was 49% (TGA 100 mg/L, P<0.05, vs. LPS) and 21% (TGA 20 mg/L, P<0.05 vs. LPS), respectively. TGA could not inhibit LPS-induced TNF-alpha production in mouse peritoneal macrophages. (2) TGA also inhibited the expression of COX-1 and COX-2 mRNA in RAW264.7 cells. The inhibitory rate of TGA to COX-1 mRNA was 22% (TGA 100 mg/L, P<0.05, vs. blank). The inhibitory rate of TGA to COX-2 mRNA was 55% (TGA 20 mg/L, P<0.05, vs. LPS) and 100% (TGA 100 mg/L, P<0.01 vs. LPS), respectively. The anti-inflammatory mechanisms of TGA for inhibiting the production of NO and PGE(2)are through inhibiting COX-2 mRNA expression without TNF-alpha changes.
Article
Powdered rooibos tea extract (RTE), which is rich in polyphenols, is made from rooibos tea by freeze-drying. "Rooibos" is Afrikaans for "red bush," and the scientific name is "Aspalathus linearis." It is a broom-like member of the legume family of plants and is used to make an herbal tea which has been popular in South Africa for generations and is now consumed in many countries. In the present work, the anti-oxidative effect of RTE on oils and fats in autoxidation or thermal oxidation was studied, and it was confirmed that RTE has a very strong anti-oxidative effect on emulsifying oils owing to the water-soluble polyphenols such as rutin and quercetin contained in RTE. RTE was found to have a strong ability to quench radicals generated in the water phase, and to confer higher thermal stability against deep fat frying than tocopherol. But RTE showed little anti-oxidative effect on frying oil because of its lower oil-solubility.
Article
VITAMIN E (α-tocopherol) and vitamin C (ascorbic acid) react rapidly with organic free radicals, and it is widely accepted that the antioxidant properties of these compounds are responsible in part for their biological activity1-5. Tissue vitamin C levels are often considerably greater than those of vitamin E, for example in liver the values are approximately 2 mM and 0.02 mM, respectively. Nevertheless, vitamin E is considerably more lipophilic than vitamin C, and in biomembranes has been found to be the more potent antioxidant, particularly with respect to lipid peroxidation; penetration to a precise site in the membrane may be an important feature of the protection against highly reactive radicals6. Tappel has suggested that the two vitamins act synergistically, vitamin E acting as the primary antioxidant and the resulting vitamin E radical then reacting with vitamin C to regenerate vitamin E7. We now report direct observation of this interaction, which we feel may be an important feature in the maintenance of vitamin E levels in tissues.
Article
Modification of low density lipoproteins (LDL) by oxidation has been shown to permit recognition by the acetyl-LDL receptor of macrophages. The extensive oxidation of LDL that is required before interaction occurs with this receptor produces major alterations in both the lipid and protein components of LDL. Several chemical modifications of LDL also lead to recognition by this receptor; all of these involve derivatization of lysine residues of apolipoprotein B by adducts that neutralize the positively charged epsilon-amino group. The present studies show that oxidation also results in derivatization of LDL lysine residues. Analysis of amino acid composition indicated that 32% of lysine residues were modified after oxidation of LDL by exposure to 5 microM CuSO4 for 20 h. About one-half of the derivatized lysines were labile under the conditions of acid hydrolysis. Fluorescence of LDL protein was greatly increased by oxidation, with excitation maximum at 350 nm and emission maximum at 433 nm. When LDL containing phosphatidylcholine with isotopically labeled arachidonic acid in the sn-2 position was oxidized, there was a 5-fold increase in radioactivity bound to protein compared to nonoxidized LDL or oxidized LDL labeled with 2-[1-14C]palmitoyl phosphatidylcholine. Prior methylation of LDL prevented the rapid uptake and degradation by macrophages that normally accompanies oxidation. These findings suggest that oxidation of LDL is accompanied by derivatization of lysine epsilon-amino groups by lipid products and that these adducts may be important in the interaction of oxidized LDL with the acetyl-LDL receptor.
Article
The role of vitamin E in the endocrine system, in particular the pituitary-gonadal axis, was studied in humans and male rats by examining the hormonal differences between vitamin E deficient and supplemented conditions. In vitamin E deficient rats, pituitary content and basal plasma level of FSH and LH were significantly lower than those of the control rats, but testicular content and basal plasma level of testosterone were not significantly changed. On the other hand, in vitamin E supplemented rats, FSH and LH content in pituitary tissue was significantly higher than that of the controls, but there was no significant rise in basal FSH and LH level in plasma. The testosterone level was significantly elevated in both testicular tissue and plasma. It was also demonstrated that basal plasma testosterone and F.T.I. were increased in normal male subjects following oral vitamin E administration and the responsiveness of plasma testosterone levels to HCG was significantly higher during vitamin E administration than before administration. These results suggest that vitamin E may play an important and potent role in hormone production in the pituitary-gonadal axis in humans and rats.
Article
Lipid peroxidation products and antioxidant enzyme activities were studied in the rat testis following exposures to cigarette smoke, polychlorinated biphenyls (PCBs), or polychlorinated naphthalenes (PCNs). Three hours after a single 1-hour period of smoke inhalation, the levels of fluorescent chromolipids and thiobarbituric acid-reactive species (TBARS) were markedly increased in the testis (+49%, P < 0.01, and +43%, P < 0.05, respectively). Twelve hours after daily smoking for 1 hour, for 1, 5, or 10 days, such an increase was not found. Activities of the antioxidant enzymes superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), glutathione transferase (GSH-Tr), or hexose monophosphate shunt (HMS) were not affected immediately, 3 hours, or 12 hours after a single smoking session. Twelve hours after smoking for 5 days, the activity of catalase was decreased (-16%, P < 0.05). Smoking exposures had no consistent effects on serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), or testosterone concentrations. Single i.p. injections of PCB or PCN mixtures resulted in decreases in testicular SOD activity 1 day after the exposures (-14%, P < 0.05, and -51%, P < 0.01, respectively). Catalase activity also decreased after both exposures (-30 to -42%, P < 0.05, at days 1-7 after PCB exposure, and -37 to -43%, P < 0.05, at days 3-7 after PCN exposure). Ninety days after the PCN exposure, activities of GSH-Px and GSH-Tr were decreased in the testis (-20%, P < 0.05, and -26%, P < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Free oxygen radicals are increasingly discussed as important factors involved in the phenomenon of biological ageing. Higher formation rates of free radicals from senescent animals observed in isolated biological materials (mainly in mitochondria), accumulation of free radical damage and changes of antioxidant capacities appear to prove the correctness of this assumption. In the present review these findings are critically examined in order to evaluate whether free radicals do contribute to the initiation and/or propagation of ageing. It is concluded that data available so far do not allow a definite answer to this question although, free radicals are very likely to contribute considerably to the development of stochastic disorders observed during the progress of ageing.
Article
Diabetes mellitus is a syndrome initially characterized by a loss of glucose homeostasis. The disease is progressive and is associated with high risk of atherosclerosis, kidney and nerve damage as well as blindness. Abnormalities in the regulation of peroxide and transition metal metabolism are postulated to result in establishment of the disease as well as its longer term complications. Diabetes mellitus is associated with oxidative reactions, particularly those which are catalyzed by decompartmentalized transition metals, but their causative significance in diabetic tissue damage remains to be established.
Article
Ischaemic myocardial tissue will, inevitably, necrose if blood flow is not restored. Whilst reperfusion is always beneficial in terms of potential recovery of heart muscle, reperfusion in itself is believed to bring about cellular injury. While the causes of this 'reperfusion injury' are apparently multifactorial, there is now an increasing body of evidence to suggest that oxygen free radicals play a major role in the pathogenesis of reperfusion injury. The initial evidence for this hypothesis was indirect, based on the ability of free radical scavengers to limit myocardial injury in animal models. More recent work has utilised the highly specific technique of electron spin resonance (ESR) spectroscopy and ESR spin trapping to detect the free radical species. The evidence for free radical production on myocardial reperfusion will be presented along with details of human studies. The potential for a therapeutic intervention will also be briefly discussed.
Article
In recent years it has become increasingly apparent that, in man, free radicals play a role in a variety of normal regulatory systems, the deregulation of which may play an important role in inflammation. As examples, we discuss the second messenger roles of: NO in the regulation of vascular tone, O2.- in fibroblast proliferation and H2O2 in the activation of transcription factors such as NF kappa B. Other control mechanisms, the physiological function of which may be perturbed in inflammation, include: the oxidative modification of low density lipoprotein, the oxidative inactivation of alpha-1-protease inhibitor, DNA damage/repair and heat shock protein synthesis. At sites of inflammation, increased free radical activity is associated with the activation of the neutrophil NADPH oxidase and/or the uncoupling of a variety of redox systems, including endothelial cell xanthine dehydrogenase. Although free radicals, thus produced, have the capacity to mediate tissue destruction, either alone or in concert with proteases, we argue that disturbances in the second messenger and regulatory activities of free radicals may also contribute significantly to the inflammatory process.
Article
Oxygen toxicity is an inherent challenge to aerobic life, including spermatozoa, the cells responsible for propagation of the species. How this toxicity affects the spermatozoan in its interactions with the ovum is still unknown. An increase in oxidative damage to sperm membranes, proteins, and DNA is associated with alterations in signal transduction mechanisms that affect fertility. Recent evidence suggests that spermatozoa and oocytes possess an inherent but limited capacity to generate ROS to aid in the fertilization process. Though a variety of defense mechanisms encompassing antioxidant enzymes (SOD, catalase, and GSH peroxidase and reductase), vitamins (E, C, and carotenoids), and biomolecules (GSH and ubiquinol) are available, a balance of the benefits and risks from ROS and antioxidants appears to be necessary for the survival and functioning of spermatozoa. An assay system for the evaluation of OSS needs to be developed. Such an assay will assist the clinician in the assessment of fertility status of both male and female partners. The determination of this OSS value will also theoretically identify the subgroups of responders and nonresponders to any putative antioxidant therapy. Though the therapeutic use of antioxidants appears attractive, clinicians need to be aware of exaggerated claims of antioxidant benefits by various commercial supplements for fertility purposes until proper multicenter clinical trial have been completed.
Article
Diets rich in fruits and vegetables are associated with decreased risk of cardiovascular disease and cancer. Biomarkers of oxidative DNA damage and lipid peroxidation can be used to establish the role of antioxidants in this protection and the optimal intake of those antioxidants. This concept is based on the presumptions that oxidative DNA damage is a significant contributor to the age-related development of some cancers and that lipid peroxidation plays a key role in the development of cardiovascular disease. Mass spectrometric measurements of various families of isoprostanes (F2-, F3-, and F4-isoprostanes) and of multiple DNA base oxidation products are probably the most promising biomarkers for use in human nutritional intervention studies. Biomarker studies should precede, as well as accompany, major intervention trials that measure disease incidence. The use of biomarkers provides a logical scientific basis for major intervention trials of antioxidants; such trials will, in turn, eventually validate or disprove the biomarker concept.
Article
There have been several reports indicating that the quality and quantity of human spermatozoa are facing a serious decline. This leads some scientists and environmentalists to believe that the human species is approaching a fertility crisis. Several factors have been claimed to be the attributable causes of the decline in male fertility potentials. These include heavy metals and various chemical agents widely used in agriculture and industry. Moreover, other physical factors such as the increased global temperature and radiation exposure as well as the biologic factors such as the contamination of phyto- and xeno-estrogen in the environment could detrimentally affect male reproductive function. These effects can result in, not only a reduction in sperm concentration, but also alterations in sexual behavior, mood disorders and the presence of genital cancers. The knowledge in male gonadal toxicity, therefore, is very useful in understanding the impact of environment to the male reproductive system. This will lead us to protective strategies to avoid the adverse effects of environmental factors on the male fertility.
Article
Lead exposure related oxidative stress has been incriminated, at least in part, to its toxic effects in different organs. The present investigation was carried out to study the ameliorative effects of antioxidant (ascorbic acid, alpha tocopherol or L-methionine) alone and antioxidant (alpha tocopherol) plus a conventional chelator (CaNa2 EDTA) on some of the parameters indicative of oxidative stress in the liver, kidney and brain in lead-exposed rats. Rats were given 0 (n=6, healthy controls) or 1 mg of Pb(2+)/kg b.w (n=30) as lead acetate solution in sterile normal saline ip for a period of 4 weeks. The ip injections were then withdrawn and lead exposed rats were randomly divided into five equal groups. Six lead-exposed rats were given no treatment during the 5th week (Pb group) to serve as positive controls. The rest four groups received either ascorbic acid, alpha tocopherol or L-methionine in the 5th week at the daily dose of 100 mg/kg b.w orally or alpha tocopherol as above plus CaNa2 EDTA at the rate of 110 mg/kg b.w twice a day ip for a period of 4 days. All the animals were sacrificed 1 day after the end of the experiment, and the liver, kidney and brain were quickly excised for the estimation of lead burden and alteration in the oxidative indices. Lead exposure for a period of 4 weeks followed by a period of 1 week to recover, resulted in significantly (P<0.05) higher accumulation of lead, associated with significant (P<0.05) increases in lipid peroxide level in the liver and brain, and non-protein bound thiol contents in the brain. Changes in the superoxide dismutase and catalase activities in lead-exposed rats did not reach statistical (P<0.05) significance. Treatment with antioxidants alone resulted in reversal of oxidative stress without significant decline in tissue lead burden. Tissue specific changes, following lead exposure and responses to the treatment with different antioxidants were recorded in the parameters of oxidative damage viz. lipid peroxide level, antioxidant enzymes and thiol contents.
Article
The aqueous suspension of Withania somnifera root powder was investigated for their in vivo and in vitro immunomodulatory properties. W. somnifera showed potent inhibitory activity towards the complement system, mitogen induced lymphocyte proliferation and delayed-type hypersensitivity reaction. Administration of W. somnifera root powder did not have a significant effect on humoral immune response in rats. Our results report immunosuppressive effect of W. somnifera root powder, thus it could be a candidate for developing as an immunosuppressive drug for the inflammatory diseases.
Article
Experimental induction of diabetes mellitus in animal models using chemical diabetogens is demonstrated to impair testicular function progressively leading to decreased fertility. Although, both steroidogenic and spermatogenic dysfunctions have been reported, the role of oxidative stress mechanism/s has been less understood. We have investigated the induction of oxidative damage during early diabetic phase in testis and epididymal sperm (ES) in mice administered an acute dose of streptozotocin (STZ). Our results show enhanced lipid peroxidation in testis (cytosol and mitochondria) and ES and increased ROS production as early as 5 days. Further, significant perturbations in the activities of antioxidant enzymes in testis/ES and enhanced protein carbonyl content were suggestive of increased oxidative stress during early diabetic phase. STZ-induced oxidative damage in both compartments was amenable for attenuation by treatment with oral supplements of either ascorbic acid (10mg/(kg(bw)day)) or taurine (1g/(kg(bw)day)). Furthermore, the oxidative impairments in testis/ES were persistent during the progressive phase (as measured at 2 and 4 weeks of sampling) and were associated with significant increase DNA damage (testis) and higher incidence of abnormal sperms. Interestingly, mating of STZ treated males sequentially for a period of 5 weeks with virgin untreated females resulted in a significant increase in the male-mediated dominant lethal-type mutations during the first 3 weeks, indicating a stage-specific genotoxic effect on post-meiotic germ cells. Based on the occurrence of oxidative impairments in STZ-treated mice both during both early and progressive phase, it is hypothesized that oxidative stress mechanisms may be wholly or in part contribute towards the development of testicular dysfunction and degeneration under situations of experimentally induced diabetes in animal models.
Article
Diabetes mellitus is associated with diabetic impairment of testicular function, ultimately leading to reduced fertility. Its etiology may involve oxidative damage by reactive oxygen substances, and protection against this damage can be offered by antioxidant supplementation. The aim of this study was to investigate the effects of intraperitoneal administration of vitamin C and E, selenium (Se), and vitamin E plus Se (COM) on concentrations of lipid peroxide (as malondialdehyde; MDA), reduced glutathione (GSH), and vitamin E concentrations and glutathione peroxidase (GSH-Px) activity in the testes of rats with diabetes induced by streptozotocin (STZ). Sixty groups were used (10 animals each) and these animals were initially allocated to two groups: control group and diabetic group. The diabetic group was subdivided into five groups as follows: diabetic control (DC), vitamin E, Se, COM, and vitamin C. Animals in the DC group and vitamin C, vitamin E, Se, and COM groups were made diabetic by the injection of STZ on 4 d after an injection of vitamins C and E, Se, and COM. Those vitamins and Se were also administered for 21 consecutive days. The MDA, vitamin E, GSH levels, and GSH-Px activities in testes were determined. Although the vitamin E concentration was higher in the control than in the DC group, the MDA levels were found to be lower in the control than in the DC group. The MDA levels in the testes samples of vitamin C, vitamin E, Se, and COM groups were lower than the DC group. However, GSH-Px activity and GSH levels in the testes were not significantly different between the control and DC groups. Vitamin E concentrations in the vitamin C, vitamin E, Se, and COM groups and GSH levels and GSH-Px activities in the Se, COM, and vitamin C groups were higher than either the control or DC group. The results indicate that reactive oxygen substances may be involved in possible testicular complications in diabetes of rats. Administration of vitamins C and E and Se reduced the testicular lipid peroxidation; these vitamins and Se had significant protective effects on testes of rats against oxidative damage in diabetes.