Toxicology of arsenate, arsenite, cadmium, lead, chromium, and nickel in testes of adult Swiss mice after chronic exposure by intraperitoneal route.

BACKGROUND: Some residues such as the heavy metals cadmium (Cd), lead (Pb), chromium (Cr VI), nickel (Ni), and arsenic (As), this last one in its oxidized forms + 5 (arsenate) and + 3 (arsenite), can cause injuries to human health, so they are currently considered environmental health emergencies. In the testis, heavy metals can cause morphological and functional damage due to constant exposure acting chronically in individuals. Thus, we aimed to determine the toxicological mechanism of As+5, As+3, Cd, Cr VI, and Ni that leads to testicular damage and establish for the first time an order of toxicity among these studied heavy metals. METHODS: Forty-two Swiss mice at reproductive age (140 days) were used, randomly distributed into seven experimental groups (n = 6). Exposure to heavy metals was weekly performed, by intraperitoneal route. Group 1 received 0.7 mL 0.9% saline (control), and the other groups received 1.5 mg/ kg of As+5, As+3, Cd, Pb, Cr VI, or Ni, for six weeks. RESULTS: These studied heavy metals did not accumulate in the testis tissue. However, exposure to Ni induced moderate pathologies in the seminiferous tubules, plus changes in the tunica propria, blood vessels, lymphatic space, and carbonyl protein levels. Cd exposure caused moderate tubular histopathologies and changes in the blood vessels and lymphatic space. Cr VI induced slight tubular histopathologies, changes in the lymphatic space, blood vessels, and SOD activity. Pb and As+3 exposure triggered moderate tubular pathologies and changes in the SOD activity and carbonyl protein levels, respectively. Finally, As+5 induced only slight tubular pathologies. CONCLUSION: The testicular histopathologies caused by the studied heavy metals are mainly triggered by changes in testicular oxidative balance. Based on our findings of histomorphological alterations, the toxicity order among the heavy metals is Ni>Cd>Cr(VI)>PbAs+3 >As+5. However, considering oxidative stress results, we propose the following testicular toxicity order for these heavy metals: Ni>As+3 > Cd>Cr(VI)>Pb>As+5. Ni exposure shows the most harmful among the heavy metals to the testis.

Chia (Salvia hispanica L.) Flour and Oil Ameliorate Metabolic Disorders in the Liver of Rats Fed a High-Fat and High Fructose Diet.

We hypothesized that the consumption of chia (Salvia hispanica L.) flour (CF) and chia oil (CO) improves metabolic disorders in the liver of Wistar rats (Rattus norvegicus domestica) fed a high-fat and high-fructose (HFHF) diet. The animals were fed a HFHF diet (n = 30) or AIN93-M standard diet (n = 10) for eight weeks. After this period, the animals fed HFHF were divided into three groups (n = 10): HFHF diet, HFHF plus 14.7% of CF, and HFHF plus 4% of CO. Histological and biochemical analyses, gene expression, protein levels related to inflammation, and oxidative stress were evaluated in the liver. The HFHF diet caused lipogenesis, liver steatosis, oxidative stress, and inflammation in the animals. The CF and CO intake increased the liver total antioxidant capacity and superoxide dismutase, decreased nitric oxide levels and liver steatosis. Furthermore, the CF and CO led to the upregulation of Cpt1a and Adipor2, respectively, whereas CF downregulated Srebf1. CO intake decreased blood glucose, triglycerides, and the animals' body weight. Chia did not show effects on mitigating liver pro-inflammatory status, which it may indicate occurs later. The addition of chia into an unbalanced diet is a good and relevant strategy to reduce liver metabolic disorders caused by the high consumption of fructose and saturated fat.

Green Tea Infusion Ameliorates Histological Damages in Testis and Epididymis of Diabetic Rats.

Green tea is a popular drink used for therapeutic purposes to mitigate the consequences of diabetes. In this study, we aimed at evaluating the potential of green tea infusion to ameliorate structural and enzymatic damages caused by hyperglycemia in the testis and epididymis of Wistar rats. For that, nondiabetic and streptozotocin-induced diabetic rats (negative control and diabetes control, respectively) received 0.6 mL of water by gavage. Another set of diabetic animals received 100 mg/kg of green tea infusion diluted in 0.6 mL of water/gavage (diabetes + green tea) daily. After 42 days of treatment, the testes and epididymides were removed and processed for histopathological analysis, micromineral determination, and enzymatic assays. The results showed that treatment with green tea infusion preserved the testicular and epididymal histoarchitecture, improving the seminiferous epithelium and the sperm production previously affected by diabetes. Treatment with green tea reduced tissue damages caused by this metabolic condition. Given the severity of hyperglycemia, there was no efficacy of the green tea infusion in maintaining the testosterone levels, antioxidant enzyme activity, and microminerals content. Thus, our findings indicate a protective effect of this infusion on histological parameters, with possible use as a complementary therapy for diabetes.

High-fat diet and caffeine interact to modulate bone microstructure and biomechanics in mice.

AIMS: Although excessive fat and caffeine intake are independent risk factors for bone microstructural and functional disturbances, their association remains overlooked. Thus, we investigated the impact of high-fat diet (HFD) and caffeine alone and combined on serum lipid profile, bone microstructure, micromineral distribution and biomechanical properties. METHODS: Forty female C57BL/6 mice were randomized into 4 groups daily treated for seventeen weeks with standard diet (SD) or HFD (cafeteria diet) alone or combined with 50 mg/kg caffeine. KEY FINDINGS: The association between HFD and caffeine reduced the weight gain compared to animals receiving HFD alone. Caffeine alone or combined with HFD increases total and HDL cholesterol circulating levels. HFD also reduced calcium, phosphorus and magnesium bone levels compared to the groups receiving SD, and this reduction was aggravated by caffeine coadministration. From biomechanical assays, HFD combined with caffeine increased bending strength and stiffness of tibia, a finding aligned with the marked microstructural remodeling of the cortical and cancellous bone in animals receiving this combination. SIGNIFICANCE: Our findings indicated that HFD and caffeine interact to induce metabolic changes and bone microstructural remodeling, which are potentially related to bone biomechanical adaptations in response to HFD and caffeine coadministration.

Cardioprotective action of chia (Salvia hispanica L.) in ovariectomized rats fed a high fat diet.

The reduction in estrogen levels is associated with the increased risk factors for cardiovascular disease development. The present study aimed to evaluate the effect of chia consumption in a standard diet (SD) or high fat diet (HFD) on ovariectomized (OVX) and non-ovariectomized (SHAM) rats, in relation to biometric measurements, oxidative stress, mineral content and ATPase enzymes in the heart. The study was conducted with 80 female Wistar rats, which received a SD or HFD for 18 weeks. During the first 7 weeks, the animals received the SD or HFD. Then, 40 rats were ovariectomized and 40 rats were SHAM operated. After recovery from surgery, the animals were allocated to 8 groups (n = 10) and they received one of the following diets for 8 weeks: SD, SD + chia, HFD and HFD + chia. In the OVX group, HFD increased weight gain, adiposity, cardiac hypertrophy, and nitric oxide (NO) and K concentration and decreased the Na+/K+ATPase activity. In combination with HFD, ovariectomy decreased the catalase activity, Mg, Cu and Zn concentration, total ATPase activity, and Na+/K+ATPase and Mg2 + ATPase activities; this group also presented higher NO, Ca, K, Fe and Mn concentration in the heart. The SHAM group fed chia presented a lower fat content in the heart. In the OVX group fed HFD, chia increased the activity of superoxide dismutase, decreased NO and maintained the content of minerals and ATPase enzymes. Thus, chia improved the biometric parameters of the heart, the antioxidant activity and maintained the content of minerals and ATPase enzymes, showing a cardioprotective action, but without reversing the deleterious effects of ovariectomy.

Green tea infusion prevents diabetic nephropathy aggravation in recent-onset type 1 diabetes regardless of glycemic control.

ETHNOPHARMACOLOGICAL RELEVANCE: Green tea, traditionally used as antidiabetic medicine, positively affects the diabetic nephropathy. It was assumed that these beneficial effects were due to the hypoglycemiant capacity of the tea, wich reduces the glycemic overload and, consequently, the advanced glycation end products rate and oxidative damage. However, these results are still controversial, since tea is not always able to exert a hypoglycemic action, as demonstrated by previous studies. AIM: Investigate if green tea infusion can generate positive outcomes for the kidney independently of glycemic control, using a model of severe type 1 diabetes. MATERIAL AND METHODS: We treated streptozotocin type 1 diabetic young rats with 100 mg/kg of green tea, daily, for 42 days, and evaluated the serum and tissue markers for stress and function. We also analyzed the ion dynamics in the organ and the morphological alterations promoted by diabetes and green tea treatment. Besides, we analyzed, by an in silico approach, the interactions of the green tea main catechins with the proteins expressed in the kidney. RESULTS: Our findings reveal that the components of green tea can interact with the proteins participating in cell signaling pathways that regulate energy metabolism, including glucose and glycogen synthesis, glucose reabsorption, hypoxia management, and cell death by apoptosis. Such interaction reduces glycogen accumulation in the organ, and protects the DNA. These results also reflect in a preserved glomerulus morphology, with improvement in pathological features, and suggesting a prevention of kidney function impairment. CONCLUSION: Our results show that such benefits are achieved regardless of the blood glucose status, and are not dependent on the reduction of hyperglycemia.

Different Routes of Administration Lead to Different Oxidative Damage and Tissue Disorganization Levels on the Subacute Cadmium Toxicity in the Liver.

The toxic effects of cadmium (Cd) on hepatic parameters are widely described in the literature. Experimental models often make use of the intraperitoneal route (i.p.) because it is easier to apply, while in the oral route, Cd poisoning in humans is best represented by allowing the metal to pass through the digestive system and be absorbed into the bloodstream. Thus, this study investigated the Cd exposure impact on the liver, by comparing both i.p. and oral routes, both in single dose, in addition to the oral route in fractional doses. Swiss adult male mice received CdCl2 1.5 mg/kg i.p., 30 mg/kg oral single dose, and 4.28 mg/kg oral route in fractional doses for 7 consecutive days. Cd bioaccumulation was observed in all animals exposed to Cd. Hepatic concentrations of Ca and Fe increased only in the fractionated oral route. Liver activities of SOD and CAT increased only by oral single dose. GST decreased in all forms of oral administration, while MDA decreased only in i.p. route. Liver weight and HSI increased in the i.p. route, while organ volume increased in all forms of oral administration, and liver density increased in all animals exposed to Cd. In hepatic histomorphometry, the changes were more evident in oral administration, mainly in exposure to metal in a single dose. Thus, the subacute administration of Cd in different routes of administration leads to different changes in liver poisoning.

Could biological tissue preservation methods change chemical elements proportion measured by energy dispersive X-ray spectroscopy?

Energy dispersive X-ray spectroscopy (EDS) is a powerful technical tool used in the biomedical field to investigate the proportion of chemical elements of interest in research, such as heavy metal bioaccumulation and the enzymatic cofactors and nanoparticle therapy in various pathologies. However, the correct evaluation of the proportion of the elements is subject to some factors, including the method of sample preservation. In this study, we seek to investigate the effect of biological tissue preservation methods on the proportion of chemical elements obtained by the EDS methodology. For such, we used EDS to measure the proportion of chemical elements with biomedical interest in preserved livers, using three common methods for preserving biological tissues: (a) freezing, (b) paraformaldehyde fixative solution, and (c) Karnovsky solution. We found an increased level of sodium and reduced contents of potassium and copper in samples fixed in fixative solutions, when compared to frozen samples (p < 0.05). Our data indicate that preservation methods can change the proportion of chemical elements in biological samples, when measured by EDS. Frozen preservation should be preferred to retain the actual chemical content of samples and allow a correct assessment of the proportion of their elements.