Opuntia spp. in Human Health: A Comprehensive Summary on Its Pharmacological, Therapeutic and Preventive Properties. Part 2.

Plants of the genus Opuntia spp are widely distributed in Africa, Asia, Australia and America. Specifically, Mexico has the largest number of wild species; mainly O. streptacantha, O. hyptiacantha, O. albicarpa, O. megacantha and O. ficus-indica. The latter being the most cultivated and domesticated species. Its main bioactive compounds include pigments (carotenoids, betalains and betacyanins), vitamins, flavonoids (isorhamnetin, kaempferol, quercetin) and phenolic compounds. Together, they favor the different plant parts and are considered phytochemically important and associated with control, progression and prevention of some chronic and infectious diseases. Part 1 collected information on its preventive actions against atherosclerotic cardiovascular diseases, diabetes and obesity, hepatoprotection, effects on human infertility and chemopreventive capacity. Now, this second review (Part 2), compiles the data from published research (in vitro, in vivo, and clinical studies) on its neuroprotective, anti-inflammatory, antiulcerative, antimicrobial, antiviral potential and in the treatment of skin wounds. The aim of both reviews is to provide scientific evidences of its beneficial properties and to encourage health professionals and researchers to expand studies on the pharmacological and therapeutic effects of Opuntia spp.

Potential protective effect of beta-caryophyllene against cadmium chloride-induced damage to the male reproductive system in mouse.

Cadmium is a metal that can affect the male reproductive process, possibly leading to infertility. In contrast, beta-caryophyllene (BC) is a sesquiterpene that has shown antigenotoxic, anticancer, and antioxidant properties. Therefore, the aim of the present study was to determine the protective effect of BC against the deleterious effects of cadmium chloride (CC) on various mouse testicular and sperm parameters. We tested three doses of BC (20, 200, and 400 mg/kg) given before and during exposure to 3 mg/kg CC (six days after a single administration). Our results show significant alleviation of the damage induced by CC after the three doses of BC. Regarding the sperm concentration and morphology, the protection with the high dose was complete, and regarding sperm mobility and viability, the protection was more than 74%. In the comet assay, the highest dose showed a reduction of 92.5% in the damage induced by CC, and regarding the number of micronuclei in the spermatids, the reduction was 83.3%. In the oxidative evaluation, regarding sperm lipoperoxidation, the improvement was complete with the high dose, and in the ABTS.+ test, the improvement in the response to the BC high dose was 26.3%. Regarding testicular lipoperoxidation and protein oxidation, the protective effects of the high BC dose were 87.6% and 89.9%, respectively. We also found that BC protected against the histological and morphometric alterations induced by CC. Therefore, our study clearly demonstrates the beneficial, chemopreventive effect of BC against the mouse sperm and testicular alterations induced by CC.

Arsenic exposure and non-carcinogenic health effects.

Inorganic arsenic (iAs) exposure is a serious health problem that affects more than 140 million individuals worldwide, mainly, through contaminated drinking water. Acute iAs poisoning produces several symptoms such as nausea, vomiting, abdominal pain, and severe diarrhea, whereas prolonged iAs exposure increased the risk of several malignant disorders such as lung, urinary tract, and skin tumors. Another sensitive endpoint less described of chronic iAs exposure are the non-malignant health effects in hepatic, endocrine, renal, neurological, hematological, immune, and cardiovascular systems. The present review outlines epidemiology evidence and possible molecular mechanisms associated with iAs-toxicity in several non-carcinogenic disorders.

Subacute and subchronic toxicity of microencapsulated pomegranate juice in rats and mice.

Pomegranate (Punica granatum L.) is a fruit used extensively in traditional medicine by ancient and modern cultures. Different parts of the tree and fruit, such as leaf, peel, pericarp, aril, seed, and juice contain considerable amounts of phenolic compounds with high antioxidant activities. To improve its storability, pomegranate juice was microencapsulated by spray drying. The present study evaluated microencapsulated pomegranate juice (MPJ) for toxic effects in Wistar rats and CD-1 mice to determine if MPJ can be considered safe for human consumption and used as a nutraceutical. No deaths or deleterious effects occurred when high doses of 5000 mg/kg were orally administered in rats for 14 days, indicating an absence of subacute toxicity. Similarly, 3000 mg/kg MPJ administered to CD-1 mice for 90 days did not show subchronic toxicity. In fact, MPJ resulted in lowered weight gain in both rats and mice. Cytotoxic and microbiological analyses of MPJ were also performed. MPJ did not cause any cytotoxicity in epithelial cell culture as tested using the Alamar blue assay. Additionally, histopathological analysis of kidney and liver corroborated the absence of toxicity in CD-1 mice. The microbial load of the MPJ was low, and no pathogenic bacteria were present. In conclusion, the results reported here show that high doses of MPJ are apparently innocuous in rats and mice for the 14 and 90 days investigated, respectively. Although preliminary, our results suggest that MPJ may be safe to ingest and may even have beneficial effects in reducing weight gain.

Asthma: New Integrative Treatment Strategies for the Next Decades.

Asthma is a chronic disease whose main anatomical-functional alterations are grouped into obstruction, nonspecific bronchial hyperreactivity, inflammation and airway remodeling. Currently, the Global Initiative of Asthma 2020 (GINA 2020) suggests classifying it into intermittent cases, slightly persistent, moderately persistent and severely persistent, thus determining the correct guidelines for its therapy. In general, the drugs used for its management are divided into two groups, those with a potential bronchodilator and the controlling agents of inflammation. However, asthmatic treatments continue to evolve, and notable advances have been made possible in biological therapy with monoclonal antibodies and in the relationship between this disease and oxidative stress. This opens a new path to dietary and herbal strategies and the use of antioxidants as a possible therapy that supports conventional pharmacological treatments and reduces their doses and/or adverse effects. This review compiles information from different published research on risk factors, pathophysiology, classification, diagnosis and the main treatments; likewise, it synthesizes the current evidence of herbal medicine for its control. Studies on integrative medicine (IM) therapies for asthmatic control are critically reviewed. An integrative approach to the prevention and management of asthma warrants consideration in clinical practice. The intention is to encourage health professionals and scientists to expand the horizons of basic and clinical research (preclinical, clinical and integrative medicine) on asthma control.

Organic Acids from Roselle (Hibiscus sabdariffa L.)-A Brief Review of Its Pharmacological Effects.

Roselle (Hibiscus sabdariffa L.), also known as jamaica in Spanish, is a perennial plant that grows in tropical and subtropical regions, including China, Egypt, Indonesia, Mexico, Nigeria, Thailand, and Saudi Arabia. It has a long history of uses, mainly focused on culinary, botanical, floral, cosmetic, and medicinal uses. The latter being of great impact due to the diuretic, choleretic, analgesic, antitussive, antihypertensive, antimicrobial, immunomodulatory, hepatoprotective, antioxidant, and anti-cancer effects. These therapeutic properties have been attributed to the bioactive compounds of the plant, mainly phenolic acids, flavonoids, anthocyanins, and organic acids (citric, hydroxycitric, hibiscus, tartaric, malic, and ascorbic). Most literature reviews and meta-analyses on the therapeutic potential of Hibiscus sabdariffa L. (Hs) compounds have not adequately addressed the contributions of its organic acids present in the Hs extracts. This review compiles information from published research (in vitro, in vivo, and clinical studies) on demonstrated pharmacological properties of organic acids found in Hs. The intent is to encourage and aid researchers to expand their studies on the pharmacologic and therapeutic effects of Hs to include assessments of the organic acid components.

Molecular Characterization of SehB, a Type II Antitoxin of Salmonella enterica Serotype Typhimurium: Amino Acid Residues Involved in DNA-Binding, Homodimerization, Toxin Interaction, and Virulence.

Salmonella enterica serotype Typhimurium is a bacterium that causes gastroenteritis and diarrhea in humans. The genome of S. Typhimurium codes for diverse virulence factors, among which are the toxin-antitoxin (TA) systems. SehAB is a type II TA, where SehA is the toxin and SehB is the antitoxin. It was previously reported that the absence of the SehB antitoxin affects the growth of S. Typhimurium. In addition, the SehB antitoxin can interact directly with the SehA toxin neutralizing its toxic effect as well as repressing its own expression. We identified conserved residues on SehB homologous proteins. Point mutations were introduced at both N- and C-terminal of SehB antitoxin to analyze the effect of these changes on its transcription repressor function, on its ability to form homodimers and on the virulence of S. Typhimurium. All changes in amino acid residues at both the N- and C-terminal affected the repressor function of SehB antitoxin and they were required for DNA-binding activity. Mutations in the amino acid residues at the N-terminal showed a lower capacity for homodimer formation of the SehB protein. However, none of the SehB point mutants were affected in the interaction with the SehA toxin. In terms of virulence, the eight single-amino acid mutations were attenuated for virulence in the mouse model. In agreement with our results, the eight amino acid residues of SehB antitoxin were required for its repressor activity, affecting both homodimerization and DNA-binding activity, supporting the notion that both activities of SehB antitoxin are required to confer virulence to Salmonella enterica.

Garlic (Allium sativum L.): A Brief Review of Its Antigenotoxic Effects.

Traditional Medicine/Complementary and Alternative Medicine is a practice that incorporates medicine based on plants, animals, and minerals for diagnosing, treating, and preventing certain diseases, including chronic degenerative diseases such as obesity, diabetes, hypertension, atherosclerosis, and cancer. Different factors generate its continued acceptance, highlighting its diversity, easy access, low cost, and the presence of relatively few adverse effects and, importantly, a high possibility of discovering antigenotoxic agents. In this regard, it is known that the use of different antigenotoxic agents is an efficient alternative to preventing human cancer and that, in general, these can act by means of a combination of various mechanisms of action and against one or various mutagens and/or carcinogens. Therefore, it is relevant to confirm its usefulness, efficacy, and its spectrum of action through different assays. With this in mind, the present manuscript has as its objective the compilation of different investigations carried out with garlic that have demonstrated its genoprotective capacity, and that have been evaluated by means of five of the most outstanding tests (Ames test, sister chromatid exchange, chromosomal aberrations, micronucleus, and comet assay). Thus, we intend to provide information and bibliographic support to investigators in order for them to broaden their studies on the antigenotoxic spectrum of action of this perennial plant.

Evidence of Some Natural Products with Antigenotoxic Effects. Part 2: Plants, Vegetables, and Natural Resin.

Cancer is one of the leading causes of death worldwide. The agents capable of causing damage to genetic material are known as genotoxins and, according to their mode of action, are classified into mutagens, carcinogens, or teratogens. Genotoxins are also involved in the pathogenesis of several chronic degenerative diseases, including hepatic, neurodegenerative, and cardiovascular disorders; diabetes; arthritis; cancer; chronic inflammation; and ageing. In recent decades, researchers have found novel bioactive phytocompounds able to counteract the effects of physical and chemical mutagens. Several studies have shown the antigenotoxic potential of different fruits and plants (Part 1). In this review (Part 2), we present a research overview conducted on some plants and vegetables (spirulina, broccoli, chamomile, cocoa, ginger, laurel, marigold, roselle, and rosemary), which are frequently consumed by humans. In addition, an analysis of some phytochemicals extracted from those vegetables and the analysis of a resin (propolis),whose antigenotoxic power has been demonstrated in various tests, including the Ames assay, sister chromatid exchange, chromosomal aberrations, micronucleus, and comet assay, was also performed.

Effects of Heliopsis longipes ethanolic extract on mouse spermatozoa in vitro.

CONTEXT: Heliopsis longipes (A. Gray) Blake (Asteraceae), a plant native to Mexico, is used in traditional medicine as analgesic and microbicide. The main component in the H. longipes ethanolic extract (HLEE) is affinin, as determined by HPLC/UV-visible and NMR measurement. To date, there is no documented evidence on the spermicidal activity of this extract. OBJECTIVE: The objective of this study was to assess in vitro the effectiveness of HLEE as spermicide. MATERIALS AND METHODS: The spermicidal activity of HLEE was evaluated by the Sander-Cramer assay. Spermatozoa were incubated for 20 s with HLEE in concentrations ranging from 75 to 2000 µg/mL to determine the minimum effective concentration (MEC) value. The 50% effective concentration (EC50) of HLEE was estimated by assaying serial dilutions from the MEC. Additionally, sperms were incubated with 125, 250, or 500 µg/mL of HLEE to evaluate the viability and the integrity of sperm membrane. Lipid peroxidation was assessed by the thiobarbituric acid reactive substances assay. RESULTS: HLEE caused an inhibition of 100% in spermatozoa motility at a MEC value of 2000 µg/mL; the EC50 value was 125 µg/mL. Additionally, exposure to HLEE at 125, 250, or 500 µg/mL for 30 min decreased sperm viability to 27%, 8%, and 2% of the control value, respectively, and significantly increased the percentage of sperms with structurally disorganized membrane. HLEE also increased significantly the level of lipid peroxidation in sperms with respect to controls. DISCUSSION AND CONCLUSION: The results demonstrate the spermicidal activity of HLEE in vitro and suggest that this action is caused by oxidative damage and alterations in the spermatozoal membrane.

Prevention of Aflatoxin B1-Induced DNA Breaks by ß-D-Glucan.

Aflatoxins are a group of naturally-occurring carcinogens that are known to contaminate different human and animal foodstuffs. Aflatoxin B1 (AFB1) is the most genotoxic hepatocarcinogenic compound of all of the aflatoxins. In this report, we explore the capacity of ß-D-glucan (Glu) to reduce the DNA damage induced by AFB1 in mouse hepatocytes. For this purpose, we applied the comet assay to groups of animals that were first administered Glu in three doses (100, 400 and 700 mg/kg bw, respectively) and, 20 min later, 1.0 mg/kg of AFB1. Liver cells were obtained at 4, 10 and 16 h after the chemical administration and examined. The results showed no protection of the damage induced by AFB1 with the low dose of the polysaccharide, but they did reveal antigenotoxic activity exerted by the two high doses. In addition, we induced a co-crystallization between both compounds, determined their fusion points and analyzed the molecules by UV spectroscopy. The data suggested the formation of a supramolecular complex between AFB1 and ß-D-glucan.

Role of ATP-sensitive K+ channels in the antinociception induced by non-steroidal anti-inflammatory drugs in streptozotocin-diabetic and non-diabetic rats.

There is evidence that systemic sulfonylureas block diclofenac-induced antinociception in normal rat, suggesting that diclofenac activates ATP-sensitive K(+) channels. However, there is no evidence for the systemic interaction between different non-steroidal anti-inflammatory drugs (NSAIDs) and sulfonylureas in streptozotocin (STZ)-diabetic rats. Therefore, this work was undertaken to determine whether two sulfonylureas, glibenclamide and glipizide, have any effect on the systemic antinociception that is induced by diclofenac (30 mg/kg), lumiracoxib (56 mg/kg), meloxicam (30 mg/kg), metamizol (56 mg/kg) and indomethacin (30 mg/kg) using the non-diabetic and STZ-diabetic rat formalin test. Systemic injections of NSAIDs produced dose-dependent antinociception during the second phase of the test in both non-diabetic and STZ-diabetic rats. Systemic pretreatment with glibenclamide (10 mg/kg) and glipizide (10 mg/kg) blocked diclofenac-induced systemic antinociception in the second phase of the test (P<0.05) in both non-diabetic and STZ-diabetic rats. In contrast, pretreatment with glibenclamide or glipizide did not block lumiracoxib-, meloxicam-, metamizol-, and indomethacin-induced systemic antinociception (P>0.05) in both groups. Results showed that systemic NSAIDs are able to produce antinociception in STZ-diabetic rats. Likewise, data suggest that diclofenac, but not other NSAIDs, activated K(+) channels to induce its systemic antinociceptive effect in the non-diabetic and STZ-diabetic rat formalin test.

Investigation on the protective effects of cranberry against the DNA damage induced by benzo[a]pyrene.

There are few reports that demonstrate the antigenotoxic potential of cranberries. Although the types of berry fruits consumed worldwide are many, this paper focuses on cranberries that are commonly consumed in Mexico (Vaccinium macrocarpon species). The purpose of the present study is to determine whether cranberry ethanolic extract (CEE) can prevent the DNA damage produced by benzo[a]pyrene (B[a]P) using an in vivo mouse peripheral blood micronucleus assay. The experimental groups were organized as follows: a negative control group (without treatment), a positive group treated with B[a]P (200 mg/kg), a group administered with 800 mg/kg of CEE, and three groups treated with B[a]P and CEE (200, 400, and 800 mg/kg) respectively. The CEE and benzo[a]pyrene were administered orally for a week, on a daily basis. During this period the body weight, the feed intake, and the determination of antigenotoxic potential were quantified. At the end of this period, we continued with the same determinations for one week more (recovery period) but anymore administration of the substances. The animals treated with B[a]P showed a weight increase after the first week of administration. The same phenomenon was observed in the lots combined with B[a]P and CEE (low and medium doses). The dose of 800 mg/kg of CEE showed similar values to the control group at the end of the treatment period. In the second part of the assay, when the substances were not administered, these experimental groups regained their normal weight. The dose of CEE (800 mg/kg) was not genotoxic nor cytotoxic. On the contrary, the B[a]P increases the frequency of micronucleated normochromatic erythrocytes (MNNE) and reduces the rate of polychromatic erythrocytes (PE) at the end of the treatment period. With respect to the combined lots, a significant decrease in the MN rate was observed from the sixth to the eighth day of treatment with the two high doses applied; the highest protection (60%) was obtained with 800 mg/kg of CEE. The same dose showed an anticytotoxic effect which corresponded to an improvement of 62.5% in relation to the animals administered with the B[a]P. In the second period, all groups reached values that have been seen in the control group animals. Our results suggest that the inhibition of clastogenicity of the cranberry ethanolic extract against B[a]P is related to the antioxidant capacity of the combination of phytochemicals present in its chemical composition.

NADPH oxidase participates in the oxidative damage caused by fluoride in rat spermatozoa. Protective role of α-tocopherol.

Fluorosis, caused by drinking water contaminated with inorganic fluoride, is a public health problem in many areas around the world. The aim of this study was to evaluate oxidative stress in spermatozoa caused by fluoride and NADPH oxidase in relationship to fluoride. Four experimental groups of male Wistar rats were administered with deionized water, NaF, at a dose equivalent to 5 mg fluoride kg⁻¹ per 24 h, NaF plus 20 mg kg⁻¹ per 24 h α-tocopherol, or α-tocopherol alone for 60 days. We evaluated several spermatozoa parameters in the four groups: standard quality analysis, superoxide dismutase (SOD) activity, the generation of reactive oxygen species (ROS), NADPH oxidase activity, TBARS formation, ultrastructural analyses of spermatozoa using transmission electron microscopy and in vitro fertilization (IVF) capacity. After 60 days of treatment, urinary excretion of fluoride was not modified by α-tocopherol. Spermatozoa from fluoride-treated rats exhibited a significant increase in the generation of ROS, accompanied by a significant increase in NADPH oxidase activity. The increase in ROS generation was significantly diminished by diphenylene iodonium, an inhibitor of NADPH oxidase activity. In contrast, a decrease in the generation of ROS, an increase in SOD activity and the prevention of TBARS formation process were observed in spermatozoa of rats exposed to fluoride plus α-tocopherol. Finally, α-tocopherol treatment prevented the IVF incapacity observed in the spermatozoa from fluoride-treated rats. These results suggest that NADPH oxidase participates in the oxidative stress damage caused by subchronic exposure to fluoride.

Pharmacovigilance of psychoactive medications in a Mexican psychiatric hospital.

Pharmacovigilance is the permanent collection and assessment of the safety data of drugs in the interest of precise knowledge of the safety profile. We monitored notifications of suspected adverse reactions (AR) produced by psychoactive medications (ARPM) in a Psychiatry Hospital, during a 4-month period. Yellow cards for adverse reaction reporting were distributed to the medical personal at the Hospital Psiquiátrico Villa Ocaranza, Pachuca Hidalgo, Mexico. For each notification, the ARPM was analyzed in order to verify causality. One hundred twelve hospitalized patients entered the study (44 male and 68 female). The mean +/- SD age of the patients was 46 +/- 4.5 years. The major diagnoses found were: schizophrenia (35.7%), severe mental retardation (17 %), moderate mental retardation (MMR)/epilepsy (12.5%), MMR (8.03%), and others (26.7%). During the study there were 721 therapeutic regimens prescribed to patients on psychiatric service. Patients were receiving an average of 5.3 +/- 1.1 (range 4 to 8) psychiatric medications. The psychiatrists reported only 5 ARPMs in five patients (prevalence: 4.46%). Among the drugs involved were neuroleptics (47.8%), antiepileptic (39.1%), and others (13.04%). The organs and systems affected by the ARs were the central nervous system, skin, endocrinological and gastrointestinal. A causal association between the medication and the AR were classified as probable in three cases, as possible in one case, as doubtful in one case and as definite in no case.

Effectiveness of diclofenac, ketorolac and etoricoxib in the treatment of acute pain from ankle fracture.

Tissue degeneration, infection, inflammation, cancer, trauma, surgery and limb fractures all produce pain. Each of these physiological abnormalities requires a therapeutic approach different from the last. In acute pain, caused by fracture, several classes of analgesics have been utilized. These basic remedies for analgesia, however, are still confined to a small number of medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), local anesthetics and opioids. In addition, most of these drugs have side effects, limiting their use in clinical practice. The purpose of this study was to compare the efficacy of three NSAIDs to relief acute pain caused by ankle fracture. Sixty subjects with ankle fracture were randomized to receive ketorolac, diclofenac, or etoricoxib, every 12 hours in a prospective, double-blind study. Forty-nine patients completed the study. The subjects' assessments of ankle pain on the visual analog scale and a Likert scale showed a significant reduction from baseline over 24 hr, regardless the treatment group. All treatments showed a similar profile in pain reduction. Etoricoxib, diclofenac and ketorolac twice daily are a rapid and effective treatment for acute pain. All the regimens were well tolerated in this study.

Pharmacological interaction between gabapentin and glibenclamide in the formalin test in the diabetic rat.

There is evidence that local peripheral administration of gabapentin produces antinociception through the activation of the ATP-sensitive K+-channel. However, this interaction has not been evaluated systemically, nor in diabetic rat. This work was undertaken to determine whether glibenclamide has any effect on the systemic antinociception induced by gabapentin. Inflammatory pain was induced by injection of formalin in diabetic rats. Reduction of flinching behavior was considered as antinociception. Systemic administration of gabapentin (10-56 mg/kg, i.p.) produced a dose-dependent antinociception in both phases of the formalin test. Also, glibenclamide (1-10 mg/kg, s.c.) blocked the gabapentin-induced antinociception. Given alone glibenclamide did not significantly modify formalin-induced nociception in diabetic rats. Our data suggest that gabapentin is able to reduce formalin-induced nociception in streptozotocin-injected rats. In addition, these data are consistent with gabapentin-mediated activation of ATP-sensitive-K+ channels to produce systemic antinociception in the formalin test in diabetic rats.

WITHDRAWN: NOX5 participates in the oxidative damage caused by fluoride in rat spermatozoa, and alpha-Tocopherol protects against this damage.

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Decreased in vitro fertility in male rats exposed to fluoride-induced oxidative stress damage and mitochondrial transmembrane potential loss.

Fluorosis, caused by drinking water contamination with inorganic fluoride, is a public health problem in many areas around the world. The aim of the study was to evaluate the effect of environmentally relevant doses of fluoride on in vitro fertilization (IVF) capacity of spermatozoa, and its relationship to spermatozoa mitochondrial transmembrane potential (DeltaPsi(m)). Male Wistar rats were administered at 5 mg fluoride/kg body mass/24 h, or deionized water orally for 8 weeks. We evaluated several spermatozoa parameters in treated and untreated rats: i) standard quality analysis, ii) superoxide dismutase (SOD) activity, iii) the generation of superoxide anion (O(2)(-)), iv) lipid peroxidation concentration, v) ultrastructural analyses of spermatozoa using transmission electron microscopy, vi) DeltaPsi(m), vii) acrosome reaction, and viii) IVF capability. Spermatozoa from fluoride-treated rats exhibited a significant decrease in SOD activity (~33%), accompanied with a significant increase in the generation of O(2)() (~40%), a significant decrease in DeltaPsi(m) (~33%), and a significant increase in lipid peroxidation concentration (~50%), relative to spermatozoa from the control group. Consistent with this finding, spermatozoa from fluoride-treated rats exhibited altered plasmatic membrane. In addition, the percentage of fluoride-treated spermatozoa capable of undergoing the acrosome reaction was decreased relative to control spermatozoa (34 vs. 55%), while the percentage fluoride-treated spermatozoa capable of oocyte fertilization was also significantly lower than the control group (13 vs. 71%). These observations suggest that subchronic exposure to fluoride causes oxidative stress damage and loss of mitochondrial transmembrane potential, resulting in reduced fertility.

Diabetogenic effects and pancreatic oxidative damage in rats subchronically exposed to arsenite.

Recent epidemiologic studies have associated chronic inorganic arsenic ((i)As) exposure with an increase in the prevalence of diabetes mellitus. Currently, the diabetogenic mechanism caused by (i)As exposure is unclear. However, it is recognized that (i)As contributes to oxidative stress in several organs and systems through generation of reactive oxygen species (ROS). ROS can function as signaling molecules to activate a number of cellular stress-sensitive pathways linked to insulin resistance and decreased insulin secretion. Male Wistar rats were administered sodium arsenite at 1.7 mg/kg (12 h), or water (controls) orally for 90 days. At the end of the 90 days of (i)As exposure hyperglycemia, hyperinsulinemia and low insulin sensitivity, evaluated by the homeostasis model assessment of insulin resistance, was observed. Arsenicals in pancreas of rats exposed to (i)As were significantly higher than the control group, being dimethyl and trimethyl metabolites the predominant arsenic species. The activity of pancreatic thioredoxin reductase was lower than the control group. Also, the levels of total glutathione and lipoperoxidation in pancreas increased significantly relative to the control group indicating the presence of stress and oxidative damage, respectively. These results represent an attempt to establish an animal model for in vivo studies of diabetogenic effects of chronic arsenic exposure.