Brazil nut consumption reduces DNA damage in overweight type 2 diabetes mellitus patients.

Type 2 diabetes mellitus (T2D) is a metabolic disease, which occurs largely due to unhealthy lifestyle. As oxidative stress is believed to promote T2D, by inducing damage to lipids, proteins, and DNA, appropriate dietary interventions seem critical to prevent, manage, and even reverse this condition. Brazil nuts (Bertholletia excelsa, H.B.K.) are nature's richest source of selenium, a mineral that has shown several health benefits. Therefore, this study aims to assess the effects of selenium consumption, through Brazil nuts, on biochemical and oxidative stress parameters, and genomic instability in T2D patients. We recruited 133 patients with T2D, registered in the Integrated Clinics of the University of Southern Santa Catarina (Brazil). Participants consumed one Brazil nut a day for six months. Blood samples and exfoliated buccal cells were collected at the beginning and the end of the intervention. The glycemic profile, lipid profile, renal profile and hepatic profile, DNA damage and selenium content were evaluated. A total of 74 participants completed the intervention. Brazil nut consumption increased selenium and GSH levels, GPx, and CAT activity while DCF and nitrites levels decreased. Total thiols increased, and protein carbonyl and MDA levels decreased. Levels of baseline and oxidative DNA damage in T2D patients were significantly decreased, as well as the frequency of micronuclei and nuclear buds. The fasting glucose levels, HDL and LDL cholesterol, and GGT levels that increased significantly in patients with type 2 diabetes were significantly reduced with nut consumption. Our results show an increase in antioxidant activity, along with reductions of protein and lipid oxidation as well as DNA damage, suggesting that Brazil nut consumption could be an ally in reducing oxidative stress and modulating the genomic instability in T2D patients.

Maternal exercise during pregnancy modulates genotoxicity caused by high fructose consumption in mice offspring.

Pregnancy is a period that is characterized by several metabolic and physiological changes and requires special attention, especially with regard to the relationship between feeding and foetal development. Therefore, the objective of this study was to evaluate whether the practice of voluntary physical exercise (VPE) in combination with chronic consumption of fructose (FRU) from the beginning of life and/or until the gestational period causes genotoxic changes in pregnant females and in their offspring. Seventy Swiss female mice received FRU in the hydration bottle and/or practiced VPE for 8 weeks (prepregnancy/pregnancy). After the lactation period, the offspring groups were separated by sex. It was observed that the consumption of FRU affected the food consumption, serum concentration of FRU, and glycemic profile in the mothers and that the VPE decreases these parameters. In addition, FRU was genotoxic in the mothers' peripheral tissues and VPE had a preventive effect on these parameters. The offspring showed changes in food consumption, serum FRU concentration, and body weight, in addition to an increase in the adiposity index in male offspring in the FRU (FRU) group and a decrease in the FRU + VPE group. FRU leads to hepatic steatosis in the offspring and VPE was able to decrease the area of steatosis. In addition, FRU led to genotoxicity in the offspring and VPE was able to modulate this effect, reducing damages. In conclusion, we observed that all interventions with VPE had nutritional, genetic, and biochemical benefits of the mother and her offspring.

Royal jelly reduce DNA damage induced by alkylating agent in mice.

Royal jelly (RJ) is a creamy white-yellow liquid that is secreted by the mandibular and hypopharyngeal glands of bees to nourish the larvae. RJ has gained increasing interest in recent years owing to its antioxidant potential. However, little is known about adequate RJ dosing and its effects on genetic material. Thus, the aim of this study was to evaluate the in vivo effects of RJ on genotoxicity and mutagenicity induced by the alkylating agent methyl methanesulfonate (MMS). In this study, 3-month-old Swiss albino male mice (N = 66) were divided into 11 groups for experimentation. Experiments were performed by administering lyophilized RJ (150 mg/kg, 300 mg/kg, and 1000 mg/kg) or water via gavage as pre- and posttreatment processes with the alkylating agent MMS. After treatment, blood samples were collected from the mice via an incision at the end of the tail to conduct comet assays at times of 24 h and 48 h posttreatment. The mice were then euthanized to remove the bone marrow for a micronucleus test. Overall, regardless of dose, RJ did not exhibit genotoxic, mutagenic activity and the administration of high doses, mainly in the form of posttreatment, presented antigenotoxic and antimutagenic actions. Further, a dose-response correlation was observed in the RJ posttreatment groups. These results demonstrate that RJ administration was effective in reversing the damage caused by the alkylating agent MMS.

Effects of obesity on neuroinflammatory and neurochemical parameters in an animal model of reserpine-induced Parkinson's disease.

Obesity is associated with low-grade chronic inflammation and oxidative stress, affecting the brain's reward system by decreasing dopaminergic neurotransmission. It is known that dopaminergic neurotransmission is also reduced in Parkinson's disease (PD), and high adiposity is considered a risk factor for the development of several neurodegenerative diseases, including PD. This study aimed to assess the effects of obesity on neuroinflammatory and neurochemical parameters in an animal model of reserpine-induced PD. The obese group showed increased inflammation and oxidative damage as well as inhibition of mitochondrial respiratory chain complexes I and II and DNA damage in the evaluated structures. The PD group did not show inflammation or mitochondrial dysfunction but exhibited oxidative damage in the hippocampus. The combination group (obesity + PD) showed reduced inflammation and oxidative stress and increased activity of complexes I and II of the mitochondrial respiratory chain in most of the analyzed structures. On the other hand, obesity + PD caused oxidative damage to proteins in the liver, prefrontal cortex, striatum, and cerebral cortex and oxidative stress in the hypothalamus, resulting in reduced catalase activity. Furthermore, the combination group showed DNA damage in blood, liver, and cerebral cortex. In conclusion, it was observed that the association of obesity and PD did not increase inflammation, oxidative stress, or mitochondrial dysfunction in most of the evaluated structures but increased oxidative damage and induced mechanisms that led to DNA damage in peripheral tissues and brain structures.

Behavioral, genetic and biochemical changes in the brain of the offspring of female mice treated with caffeine during pregnancy and lactation.

The intrauterine environment is a critical location for exposure to exogenous and endogenous factors that trigger metabolic changes through fetal programming. Among the external factors, chemical compounds stand out, which include caffeine, since its consumption is common among women, including during pregnancy. Thereby, the aim of the present study was to evaluate the behavioral, genetic, and biochemical parameters in the offspring of female mice treated with caffeine during pregnancy and lactation. Swiss female mice (60 days old) received tap water or caffeine at 0.3 or 1.0 mg/mL during copulation (7 days), pregnancy (21 days) and lactation (21 days). After the end of the lactation period, the offspring were divided into groups (water, caffeine 0.3 or 1.0 mg/mL) with 20 animals (10 animals aged 30 days and 10 animals aged 60 days per group per sex). Initially, the offspring were submitted to behavioral tasks and then euthanized for genetic and biochemical analysis in the brain (cortex, striatum, and hippocampus). Behavioral changes in memory, depression, and anxiety were observed in the offspring: 30-day-old female offspring at 1.0 mg /mL dose presented anxiogenic behavior and male offspring the 0.3 mg/mL dose at 30 days of age did not alter long-term memory. Furthermore, an increase in DNA damage and oxidative stress in the brain were observed in the offspring of both sexes. Furthermore, there were changes in Ape-1, BAX, and Bcl-2 in the female offspring hippocampus at 30 days of life. Thus, with this study, we can suggest genotoxicity, oxidative stress, and behavioral changes caused by caffeine during pregnancy and lactation in the offspring that were not treated directly, but received through their mothers; thus, it is important to raise awareness regarding caffeine consumption among pregnant and lactating females.

Effects of Ethanolic Extract of Cynara cardunculus (Artichoke) Leaves on Neuroinflammatory and Neurochemical Parameters in a Diet-Induced Mice Obesity Model.

This study aimed to evaluate the effect of Cynara cardunculus leaf ethanol extract on inflammatory and oxidative stress parameters in the hypothalamus, prefrontal cortex, hippocampus, striatum, cerebral cortex and liver of high-fat diet-induced obese mice. Food intake, body weight, visceral fat weight, and liver weight were also evaluated. Male Swiss mice were divided into control (low-fat purified diet) and obese (high-fat purified diet) groups. After 6 weeks, mice were divided into control + saline, control + C. cardunculus leaf ethanol extract, obese + saline, obese + C. cardunculus leaf ethanol extract. Cynara cardunculus leaf ethanol extract (1600 mg/kg/day) or saline was administered orally for 4 weeks. Brain structures (hypothalamus, hippocampus, prefrontal cortex, striatum and cerebral cortex) and liver were removed. Treatment with C. cardunculus leaf ethanol extract did not affect body weight but did reduce visceral fat. Obesity can cause inflammation and oxidative stress and increase the activity of antioxidant enzymes in brain structures. Treatment with ethanolic extract of C. cardunculus leaves partially reversed the changes in inflammatory damage parameters and oxidative damage parameters and attenuated changes in the antioxidant defense. The C. cardunculus leaf ethanol extract benefited from the brains of obese animals by partially reversing the changes caused by the consumption of a high-fat diet and the consequent obesity. These results corroborate those of studies indicating that the C. cardunculus leaf ethanol extract can contribute to the treatment of obesity.

Brazil nut prevents oxidative DNA damage in type 2 diabetes patients.

The Brazil nut (Bertholletia excelsa, H.B.K.) originating from the Amazon region is one of the richest known sources of selenium (Se), a micronutrient that is essential and required for optimal physiological functioning. This mineral presents several health benefits, including improvement of the redox cellular status and maintenance of genomic stability. Knowing that type 2 diabetes mellitus (T2D) is strongly linked to oxidative stress and consequently DNA damage, the aim of this study was to assess the ex vivo antioxidative effects of Se through Brazil nut consumption and its potential in preventing oxidative DNA damage induced by H2O2. In order to accomplish this, the Comet assay (single-cell gel electrophoresis) was used to measure DNA damage in peripheral blood cells harvested before and after supplementation with Brazil nut. Comet assay was also applied ex vivo to measure the potential of Se to prevent oxidative damage to DNA induced by H2O2 in blood of type 2 diabetes patients collected before and after six months of supplementation with Brazil nut. We found that supplementation with Brazil nuts significantly increased serum Se levels. Furthermore, we observed a significant increase in fasting blood glucose after six months of consuming Brazil nuts; however, no significant effect was observed on the levels of glycated hemoglobin. Finally, we noticed that the cells were more resistant to H2O2-induced DNA damage after six months of supplementation with Brazil nut. Thus, consumption of Brazil nuts could decrease oxidative DNA damage in T2D patients, probably through the antioxidative effects of Se.

Metabolic programming in offspring of mice fed fructose during pregnancy and lactation.

Fructose (C6H12O6), also known as levulose, is a hexose. Chronic consumption of fructose may be associated with increased intrahepatic fat concentration and the development of insulin resistance as well as an increase in the prevalence of nonalcoholic fatty liver disease and hyperlipidemia during pregnancy. Despite the existence of many studies regarding the consumption of fructose in pregnancy, its effects on fetuses have not yet been fully elucidated. Therefore, the objective of this study was to evaluate the genetic and biochemical effects in offspring (male and female) of female mice treated with fructose during pregnancy and lactation. Pairs of 60-day-old Swiss mice were used and divided into three groups; negative control and fructose, 10%/l and 20%/l doses of fructose groups. After offspring birth, the animals were divided into six groups: P1 and P2 (males and females), water; P3 and P4 (males and females) fructose 10%/l; and P5 and P6 (males and females) fructose 20%/l. At 30 days of age, the animals were euthanized for genetic and biochemical assessments. Female and male offspring from both dosage groups demonstrated genotoxicity (evaluated through comet assay) and oxidative stress (evaluated through nitrite concentration, sulfhydril content and superoxide dismutase activity) in peripheral and brain tissues. In addition, they showed nutritional and metabolic changes due to the increase in food consumption, hyperglycemia, hyperlipidemia, and metabolic syndrome. Therefore, it is suggested that high consumption of fructose by pregnant female is harmful to their offspring. Thus, it is important to carry out further studies and make pregnant women aware of excessive fructose consumption during this period.

Anti-genotoxic and anti-mutagenic effects of melatonin supplementation in a mouse model of melanoma.

Melanoma, an aggressive skin cancer originating from melanocytes, can metastasize to the lungs, liver, cortex, femur, and spinal cord, ultimately resulting in DNA mutagenic effects. Melatonin is an endogenous hormone and free radical scavenger that possesses the ability to protect the DNA and to exert anti-proliferative effects in melanoma cells. The aim of this study was to evaluate the effects of B16F10 melanoma cells and the effects of melatonin supplementation on genotoxic parameters in murine melanoma models. Thirty-two male C57Bl/6 mice were divided in the following four groups: PBS + vehicle (n = 6), melanoma + vehicle (n = 10), PBS + melatonin (n = 6), and melanoma + melatonin (n = 10). The melanoma groups received a B16F10 cell injection, and melatonin was administered during 60 days. After treatment, tumor sizes were evaluated. DNA damage within the peripheral blood, lungs, liver, cortex, and spinal cord was determined using comet assay, and the mutagenicity within the bone marrow was determined using the micronucleus test. B16F10 cells effectively induced DNA damage in all tissues, and melatonin supplementation decreased DNA damage in the blood, liver, cortex, and spinal cord. This hormone exerts anti-tumor activity via its anti-proliferative, antioxidative, and pro-apoptotic effects. As this result was not observed within the lungs, we hypothesized that melatonin can induce apoptosis in cancer cells, and this was not evaluated by comet assay. This study provides evidence that melatonin can reduce the genotoxicity and mutagenicity caused by B16F10 cells.

Melatonin supplementation over different time periods until ageing modulates genotoxic parameters in mice.

The ageing process is a multifactorial phenomenon, associated with decreased physiological and cellular functions and an increased propensity for various degenerative diseases. Studies on melatonin (N-acetyl-5-methoxytryptamine), a potent antioxidant, are gaining attention since melatonin production declines with advancing age. Hence, the aim of this study was to evaluate the effects of chronic melatonin consumption on genotoxic and mutagenic parameters of old Swiss mice. Herein, 3-month-old Swiss albino male mice (n = 240) were divided into eight groups and subdivided into two experiments: first (three groups): natural ageing experiment; second (five groups): animals that started water or melatonin supplementation at different ages (3, 6, 12 and 18 months) until 21 months. After 21 months, the animals from the second experiment were euthanized to perform the comet assay, micronucleus test and western blot analysis. The results demonstrated that melatonin prolonged the life span of the animals. Relative to genomic instability, melatonin was effective in reducing DNA damage caused by ageing, presenting antigenotoxic and antimutagenic activities, independently of initiation age. The group receiving melatonin for 18 months had high levels of APE1 and OGG1 repair enzymes. Conclusively, melatonin presents an efficient antioxidant mechanism aiding modulating genetic and physiological alterations due to ageing.

Fructose consumption during pregnancy and lactation causes DNA damage and biochemical changes in female mice.

The consumption of fructose during pregnancy can cause hyperglycaemia and may stimulate production of reactive oxygen species; however, there are only a few studies reporting whether fructose consumption during pregnancy causes DNA damage. Therefore, the aim of this study was to evaluate the effects of fructose consumption on genetic and biochemical parameters in Swiss mice treated during pregnancy and lactation. For this, 15 couples of 60-day-old Swiss mice were divided into three groups of five couples: negative control (water) and two fructose groups (fructose dose of 10%/l and 20%/l). During this period, we evaluated food consumption, energy efficiency and body weight. Samples of blood were collected from the females before copulation, after the 15th day of conception and on the 21st day after the lactation period, for the glycaemic and lipid profiles as well as comet assay and micronucleus (MN) test. Comet assay and MN test evaluate DNA damage and clastogenicity, respectively. In the gestation and lactation period, the two fructose doses tested showed DNA damage as observed in the comet assay, which is associated with an increase in dietary intake, body weight, lipid profile and fasting glycaemia in females. Thus, it can be suggested that the high consumption of fructose during these periods is harmful for pregnancy and lactation.

Evaluation of genotoxicity and coumarin production in conventional and organic cultivation systems of Mikania glomerata Spreng.

Mikania glomerata Sprengel, popularly known as "guaco," is used in Brazilian folk medicine for several inflammatory and allergic conditions. Besides, the popular use "guaco" is indicated by the Brazilian Ministry of Health as a safe and effective herbal medicine. The biological activity of M. glomerata extracts is due to the presence of the coumarins, a large family of phenolic substances found in plants and is made of fused benzene and α-pyrone rings. Considering that there are few data on the biological effects of the extracts of M. glomerata, mainly in genetic level, this work aims to evaluate, in vitro, the genotoxicity and coumarin production in M. glomerata in conventional and organic growing. The data showed that the organic culture system showed double the concentration of coumarin being significantly more productive than the conventional system. Besides, the results of comet assay suggest that extracts of M. glomerata cultivated in a conventional system was genotoxic, increased DNA damage levels while the organic extracts seem to have antigenotoxic effect possibly due to the concentration of coumarins. Additional biochemical investigations are necessary to elucidate the mechanisms of action of M. glomerata extracts, which were found to have a role in protection against DNA damage.

TsNTxP, a non-toxic protein from Tityus serrulatus scorpion venom, induces antinociceptive effects by suppressing glutamate release in mice.

Neuropathic pain is a common type of chronic pain caused by trauma or chemotherapy. However, this type of pain is undertreated. TsNTxP is a non-toxic protein isolated from the venom of the scorpion Tityus serrulatus, and it is structurally similar to neurotoxins that interact with voltage-gated sodium channels. However, the antinociceptive properties of this protein have not been characterized. The purpose of this study was to investigate the antinociceptive effects of TsNTxP in acute and neuropathic pain models. Male and female Swiss mice (25-30 g) were exposed to different models of acute pain (tail-flick test and nociception caused by capsaicin intraplantar injection) or neuropathic pain (chronic pain syndrome induced by paclitaxel or chronic constriction injury of the sciatic nerve). Hypersensitivity to mechanical or cold stimuli were evaluated in the models of neuropathic pain. The ability of TsNTxP to alter the release of glutamate in mouse spinal cord synaptosomes was also evaluated. The results showed that TsNTxP exerted antinociceptive effects in the tail-flick test to a thermal stimulus and in the intraplantar capsaicin administration model. Furthermore, TsNTxP was non-toxic and exerted antiallodynic effects in neuropathic pain models induced by chronic constriction injury of the sciatic nerve and administration of paclitaxel. TsNTxP reduced glutamate release from mouse spinal cord synaptosomes following stimulation with potassium chloride (KCl) or capsaicin. Thus, this T. serrulatus protein may be a promising non-toxic drug for the treatment of neuropathic pain.

Antinociceptive activity of Copaifera officinalis Jacq. L oil and kaurenoic acid in mice.

Copaifera officinalis L. possesses traditional uses as an analgesic, anti-inflammatory, and antiseptic. However, until now the antinociceptive effect and the mechanism of action were not described for Copaifera officinalis L. oil and no compound present in this oil was identified to be responsible for its biological effects. The goal of this study was to identify the presence of kaurenoic acid in Copaifera officinalis oil and investigate its antinociceptive effect, mechanism of action, and possible adverse effects in mice. The quantification of kaurenoic acid in Copaifera officinalis oil was done by HPLC-DAD technique. Male and female albino Swiss mice (25-35 g) were used to test the antinociceptive effect of Copaifera officinalis (10 mg/kg, intragastric) or kaurenoic acid (1 mg/kg) in the tail-flick test, intraplantar injection of capsaicin, allyl isothiocyanate (AITC) or complete Freund's adjuvant (CFA). Copaifera officinalis oil and kaurenoic acid caused the antinociceptive effect in the tail-flick test in a dose-dependent manner, and their effect was reversed by naloxone (an opioid antagonist). Copaifera officinalis oil or kaurenoic acid reduced the nociception caused by capsaicin or AITC and produced an anti-allodynic effect in the CFA model (after acute or repeated administration for 7 days). Possible adverse effects were also observed, and non-detectable adverse effect was observed for the intragastric administration of Copaiba officinalis oil or kaurenoic acid and in the same way, the treatments were neither genotoxic nor mutagenic at the doses tested. Thus, Copaiba officinalis oil, and kaurenoic acid possess antinociceptive action without adverse effects.

Genotoxicity of the vegetables juice grown in garden built on the tailings coal deposits.

The aim of the present study was to evaluate the genotoxic effect of lettuce (Lactuca sativa L.), beet (Beta vulgaris L.), broccoli (Brassica oleracea var. italica), and kale (Brassica oleracea var. acephala) grown in vegetable garden built on the deposits of coal tailings. For this, we used 72 healthy male Swiss albino mice that received juice from the vegetables in an acute or chronic treatment. Using comet assay, we determined that acute administration of the juices of all vegetables from the coal-mining area was genotoxic, and increased the DNA damage in the blood, liver, and cerebral cortex of mice. Therefore, the present data suggest that intake of vegetables cultivated over coal waste results in an increase in DNA damage in some organs; this situation may pose a risk to health.

Vitamin D3 as adjuvant in the treatment of type 2 diabetes mellitus: modulation of genomic and biochemical instability.

Type 2 diabetes mellitus has undergone a worldwide growth in incidence in the world and has now acquired epidemic status. There is a strong link between type 2 diabetes and vitamin D deficiency. Because vitamin D has beneficial effects on glucose homeostasis, the aim of this study was to evaluate the influence of vitamin D3 supplementation on the modulation of glycaemic control and other metabolic effects, as well as modulation of genomic instability in patients with type 2 diabetes. We evaluated 75 patients with type 2 diabetes, registered in the Integrated Clinics of the University of Southern Santa Catarina. Participants received 4000 IU of vitamin D3 (25(OH)D) supplementation daily for 8 weeks. Blood samples were collected at the beginning and at the end of the supplementation, and 4 weeks after the end of supplementation. The glycidic and lipid profiles [total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein and triglycerides], oxidative stress, DNA damage and 25(OH)D levels were evaluated. Vitamin D3 supplementation for 8 weeks showed enough to significantly increase blood levels of 25(OH)D. A significant difference in lipid profile was observed only in non-HDL cholesterol. Significant changes were observed in glucose homeostasis (fasting glucose and serum insulin) and, in addition, a reduction in the parameters of oxidative stress and DNA damage. There was a significant reduction in the values of 25(OH)D 4 weeks after the end of the supplementation, but levels still remained above baseline. Use of vitamin D supplementation can be an ally in the health modulation of patients with type 2 diabetes mellitus.

Caffeine Neuroprotection Decreases A2A Adenosine Receptor Content in Aged Mice.

Caffeine is a bioactive compound worldwide consumed with effect into the brain. Part of its action in reducing incidence or delaying Alzheimer's and Parkinson's diseases symptoms in human is credited to the adenosine receptors properties. However, the impact of caffeine consumption during aging on survival of brain cells remains debatable. This work, we investigated the effect of low-dose of caffeine on the ectonucleotidase activities, adenosine receptors content, and paying particular attention to its pro-survival effect during aging. Male young adult and aged Swiss mice drank water or caffeine (0.3 g/L) ad libitum for 4 weeks. The results showed that long-term caffeine treatment did not unchanged ATP, ADP or AMP hydrolysis in hippocampus when compared to the mice drank water. Nevertheless, the ATP/ADP hydrolysis ratio was higher in young adult (3:1) compared to the aged (1:1) animals regardless of treatment. The content of A1 receptors did not change in any groups of mice, but the content of A2A receptors was reduced in hippocampus of mice that consumed caffeine. Moreover, the cell viability results indicated that aged mice not only had increased pyknotic neurons in the hippocampus but also had reduced damage after caffeine treatment. Overall, these findings indicate a potential neuroprotective effect of caffeine during aging through the adenosinergic system.

Sodium butyrate improves memory and modulates the activity of histone deacetylases in aged rats after the administration of d-galactose.

Aging is a complex biological process. Epigenetic alterations have been related to both aging and memory decline. Included amongst these alterations is histone acetylation, which may play a crucial role in aging. Thus, the aims of the present study were to standardize the animal model of d-galactose (d-gal), and to evaluate the effects caused by sodium butyrate (SB), which is a histone deacetylase inhibitor on memory, the modulation of histone deacetylases (HDACs), and also DNA damage in 2, 6 or 16-month-old Wistar rats which were subjected to administrations of d-gal. To help choose the best dose of d-gal for the induction of the aging model, we performed a dose-response curve (100, 200 or 300 mg/kg). d-Gal was administered orally to the 2-month-old rats for a period of 30 days. After this, d-gal (200 mg/kg) or water were administered to the 2, 6 or 16-month-old rats for a period of 30 days. On the 24th day, treatment was started with SB (600 mg/kg) intraperitoneally, for a period of 7 days. SB was able to reverse the damage to habituation memory caused by d-gal in the 2 and 6-month-old rats, but was unable to reverse the damage in the 16 month-old animals. In addition, SB was able to reverse the damage caused by natural aging in the 16-month-old animals. In the inhibitory avoidance task, SB improved the damage caused by d-gal in the 2, 6 and 16-month-old animals and had the same result against the effects of natural aging in the 16-month-old rats. Moreover, d-gal caused an increase in the level of HDACs activity in the 16-month-old animals, and SB was able to reverse this effect in the frontal cortex and hippocampus. The 16-month-old animals showed an increase in the frequency of DNA damage in peripheral blood, and SB was able to reduce this damage. Moreover, d-gal caused an increase in the index and frequency of DNA damage in the 2 and 6-month-old animals, and treatment with SB was able to prevent this damage. Thus, the present study showed the protective effects of SB on the memory of naturally aged and d-gal induced aging in rats. Therefore, the present study shows new findings for the use of SB in aging.

Genotoxicity evaluation induced by Tityus serrulatus scorpion venom in mice.

Tityus serrulatus is the scorpion associated with the most severe cases of scorpion envenoming in Brazil. However, there are no studies reporting the genotoxic effects of this venom in natural or experimental envenomations. It is well known that DNA-damage responses are providing opportunities for improving disease detection and management. In this study was evaluating the genotoxicity of the T. serrulatus venom in different organs (hippocampus, cortex, striatum, blood, heart, lung, liver and kidney) and periods in mice experimentally envenomed. ELISA and the Comet assays were used to quantification of venoms antigens and DNA damage, respectively. Forty-eight Swiss mice were divided into five groups and 0.5 DL50 of T. serrulatus venom (0.90 mg/kg) was administered intraperitoneally in each animal. Euthanasia was performed by cervical dislocation in the period of 0h (control group) 1h, 2h, 6h and 12h, where it the tissues were removed. The results showed high DNA damage in all structures analyzed, suggesting that T. serrulatus venom presented genotoxic activity or some secondary effect generated by venom injection. In the ELISA test, toxic circulant antigens were verified in practically all organs at the time intervals analyzed. Therefore, the distribution of the venom changes from organ to organ. We conclude that scorpion envenoming affects DNA in all organs analyzed even when the venom concentration is lower or no detectable, DNA damage persists.