Exposure Of Wistar Rats Research Articles

Alterations of Kiss 1 receptor, GnRH receptor and nuclear receptors of the hypothalamo-pituitary-ovarian axis following low dose bisphenol-A exposure in Wistar rats.

Bisphenol A is a chemical used primarily as a monomer in the production of polycarbonate plastics and epoxy resins. It is a synthetic chemical compound that is produced in billions of pounds annually, and tagged as an endocrine disruptor. Bisphenol A is a high production synthetic chemical compound that is used in the production of many consumables and equipments of daily consumption and use by man. Growing interest in possible health threats posed by endocrine disrupting chemicals (bisphenol-A inclusive), as these substances are in our environment, food, and many consumer products. Therefore, this study aims to determine bisphenol-A effects on the hypothalamo-pituitary-ovarian axis, and role of melatonin in this regard. Forty-two Wistar rats were bred, grouped into 7, with each group consisting of 6 rats. Experimental groups were administered low and high doses of bisphenol-A and melatonin, starting from day 19, and was continued for 7 weeks orally. They were left to develop into full adults and were sacrificed on day 120±4 days. Blood samples, hypothalamus, pituitary and ovarian tissues were excised for biochemical and tissue antioxidants assays as well as genetic studies. Results show elevated gonadotropin and androgen levels. There was disruption of reactive oxygen species in the ovarian tissues, as well as alterations in the expression of genes that regulate reproduction at the hypothalamus and pituitary levels. Conclusion of early exposure to bisphenol-A is associated with prolonged duration of disruption of reproductive functions in female Wistar rats, which persist long after cessation of the exposure. Melatonin antioxidant effects give some promising outturns against bisphenol-A induced toxicities.

Subregion-specific effects on striatal neurotransmission and dopamine-signaling by acute and repeated amphetamine exposure

Repeated administration of psychostimulants, such as amphetamine, is associated with a progressive increased sensitivity to some of the drug's effects, but tolerance towards others. We hypothesized that these adaptations in part could be linked to differential effects by amphetamine on dopaminergic signaling in striatal subregions. To test this theory, acute and long-lasting changes in dopaminergic neurotransmission were assessed in the nucleus accumbens (nAc) and the dorsomedial striatum (DMS) following amphetamine exposure in Wistar rats. By means of in vivo microdialysis, dopamine release induced by local administration of amphetamine was monitored in nAc and DMS of amphetamine naïve rats, and in rats subjected to five days of systemic amphetamine administration (2.0 mg/kg/day) followed by two weeks of withdrawal. In parallel, ex vivo electrophysiology was conducted to outline the effect of acute and repeated amphetamine exposure on striatal neurotransmission. The data shows that amphetamine increases dopamine in a concentration-dependent and subregion-specific manner. Furthermore, repeated administration of amphetamine followed by abstinence resulted in a selective decrease in baseline dopamine in the nAc, and a potentiation of the relative dopamine elevation after systemic amphetamine in the same area. Ex vivo electrophysiology demonstrated decreased excitatory neurotransmission in brain slices from amphetamine-treated animals, and a nAc selective shift in the responsiveness to the dopamine D2-receptor agonist quinpirole. These selective effects on dopamine signaling seen in striatal subregions after repeated drug exposure may partially explain why tolerance develops to the rewarding effects, but not towards the psychosis inducing properties of amphetamine.

Hibiscus sabdariffa Linn extract possesses potential to ameliorate chlorpyriphos-induced haemotoxicity in rats

Introduction: Several plants species are reported to have wealth of nutraceuticals that can be used to mitigate the detrimental effects of exposure to environmental contaminants. This study assessed the effect of Hibiscus sabdariffa (HS) on haematological changes from sub-chronic chlorpyriphos (CP) administration in male Wistar rats. Methods: Forty-two adult male Wistar rats divided into six groups: 1 (DW), II (S/oil), III (AEHS) and IV (CP) were dosed with distilled water (2 ml/kg), soya oil (2 ml/kg), high aqueous extract of H. sabdariffa (HAEHS) (500 mg/kg) only and chlorpyriphos (10.6 mg/kg ~1/8th of the LD50), respective-ly. Group V (LAEHS + CP) was pre-treated with a low dose of AEHS (250 mg/kg) before exposure to CP (10.6 mg/kg) while group VI (HAEHS + CP) rats were prior treated with a high dose of AEHS (500 mg/kg) and then exposed to CP (10.6 mg/kg). All groups were made up of seven rats each. The regi-mens were administered once daily via gavage for eleven weeks. Blood samples collected from each rat were analysed for packed cell volume (PCV), erythrocyte count, haemoglobin (Hb), leuco-cytes (total and absolute differential), platelets and erythrocytic indices. Erythrocyte lysate was also used to determine erythrocytes malondialdehyde (MDA) concentration. Results: The study shows that prior treatment with H. sabdariffa mitigated the alterations in haemato-logical and lipoperoxidation changes induced by sub chronic CP exposure in Wistar rats. Significance: Hibiscus sabdariffa possess detoxifying and antidotal potential to CP and could be used if properly explored and refined.

Evaluation of Age Related Changes Associated with Exposure of Wistar Rats to Dichlorvor on some Haematological Parameters

Different studies proved that exposure over prolonged periods to pesticides increase the likelihood of developing adverse effects. 2,2-dichlorovinyl dimethyl phosphate (DDVP) is a predominant pesticide used in controlling insects. Therefore this study was aimed to investigate the age related changes in hematological indices of animals exposed to DDVP. Thirty healthy male Wistar rats were used in this study. Animals were grouped into three major groups of ten animals each. Group one animals served as young group (5 - 6 weeks) while group two and three was the middle-aged (2 months) and old groups (3-4 months) respectively. All the groups were subdivided into control and DDVP group with five animals in each subgroup. The DDVP groups were exposed to DDVP for five weeks. At the end of fifth week, they were euthanized with blood collected through cardiac puncture, hematological indices were analysed with autohematological analyzer.Exposure to DDVP significantly increased white blood cell counts and basophiles in old group. Platelets count and plateletcrit (PCT) were significantly decreased in young animals that were exposed to DDVP while platelet distribution width (PDW) and Mean platelets volume (MPV) were not significantly different across the groups. Red blood cells count, Hematocrit, Hemoglobin concentration, Mean cell volume, Mean cell hemoglobin and Mean cell hemoglobin concentration also show no significant difference across groups. Exposure of Wistar rats to Dichlorvos has no impact on haematological parameters in middle agerats. However, dichlorvos affects young and old animals proving age dependent effect of DDVP on hematological parameters.
 Keywords: DDVP, hematology, white blood cells, platelet, age

Toxicological Assessment of Ethanolic Leaves Extract of Kalanchoe pinnata in Rats

Kalanchoe pinnata is a perennial plant that is widely used in the folklore treatment of kidney and gallstones and urinary insufficiency. The present study aims to evaluate the potential toxicity of the leaf extractof this plant upon acute and sub-acute (28 day) exposure in Wistar rats when administered orally. In acuteoral toxicity(n=3) female Wistar rats were treated with a single dose of 2000mg/kg b.wt and observed for14 days and sub-acute toxicity(n=6) male and female Wistar rats were treated with the dose of 500 and1000mg/kg b.wt of leaf extract for 28 days consecutively. No mortality, morbidity or adverse clinical signsof toxicity were observed during the experimental period. No significant changes in the body weight wasobserved. Gross necropsy did not indicate any treatment-related pathological changes in any of the animalsin the acute and sub-acute toxicity studies. Histopathology of the liver, heart and kidney did not show anyremarkable lesions that could be related to the administration of the leaf extract. Ethanolic leaf extract ofKalanchoe pinnata is relatively safe with an LD50 value greater than 2000 mg/kg. From the sub-acute study,the no-observed adverse effects level (NOAEL) of the extract can be derived as 1000 mg/kg b.wt in maleand female Wistar rats.

Toxicological Assessment of Ethanolic Leaves Extract of Kalanchoe pinnata in Rats

Kalanchoe pinnata is a perennial plant that is widely used in the folklore treatment of kidney and gallstones and urinary insufficiency. The present study aims to evaluate the potential toxicity of the leaf extractof this plant upon acute and sub-acute (28 day) exposure in Wistar rats when administered orally. In Acuteoral toxicity(n=3) Female Wistar rats were treated with a single dose of 2000mg/kg b.wt and observed for14 days and Sub-acute toxicity(n=6) Male and Female Wistar rats were treated with the dose of 500 and1000mg/kg b.wt of leaf extract for 28 days consecutively. No mortality, morbidity or adverse clinical signsof toxicity were observed during the experimental period. No significant changes in the body weight wasobserved. Gross necropsy did not indicate any treatment-related pathological changes in any of the animalsin the acute and sub-acute toxicity studies. Histopathology of the Liver, Heart and Kidney did not show anyremarkable lesions that could be related to the administration of the leaf extract. Ethanolic leaf extract ofKalanchoe pinnata is relatively safe with an LD50 value greater than 2000 mg/kg. From the sub-acute study,the no-observed adverse effects level (NOAEL) of the extract can be derived as 1000 mg/kg b.wt in maleand female Wistar rats.

Sodium metavanadate treatment improves glycogen levels in multiple tissues in a model of metabolic syndrome caused by chronic cadmium exposure in Wistar rats.

Cadmium, one of the more hazardous environmental contaminants, has been proposed as a metabolic disruptor. Vanadium has emerged as a possible treatment for metabolic diseases. Both metals are important in public health. We aimed to investigate whether vanadium treatment is effective against metabolic disturbances caused by chronic exposure to the lowest-observable adverse effect level of cadmium. Male Wistar rats were exposed to cadmium (32.5ppm) in drinking water for 3months. Metabolic complications such as overweight, visceral adipose gain, hyperglycemia, impaired glucose tolerance, and dyslipidemia were detected, and low glycogen levels and steatosis were observed in the tissues. Then, the control and treated animals were subdivided and treated with a solution of 5μM NaVO3/kg/twice a week for 2months. The control-NaVO3 group did not show zoometric or metabolic changes. A strong interaction of NaVO3 treatment over cadmium metabolic disruption was observed. The vanadium accumulation diminished cadmium concentration in tissues. Also, vanadium interaction improved glucose homeostasis. The major effect was observed on glycogen synthesis, which was fully recovered in all tissues analyzed. Additionally, vanadium treatment prevented overweight and visceral fat accumulation, improving BMI and the percentage of fat. However, NaVO3 treatment did not have an effect on dyslipidemia or steatosis. In conclusion, this work shows that vanadium administration has a strong effect against metabolic disturbances caused by chronic cadmium exposure, observing powerful interaction on glucose homeostasis.

Kaempferol and zinc gluconate mitigate neurobehavioral deficits and oxidative stress induced by noise exposure in Wistar rats.

This study investigated the effects of kaempferol and zinc gluconate on neurobehavioural and oxidative stress changes in Wistar rats exposed to noise. Thirty (30) rats were randomly divided into five groups: Groups I and II were administered with deionized water (DW); Group III, kaempferol (K); Group IV, zinc gluconate (Zn); Group V, kaempferol + zinc gluconate. Groups II, III, IV, and V were subjected to noise stress (N) induced by exposing rats to 100 dB (4 h/day) for 15 days, from day 33 to day 48 after starting the drug treatments. Neuromuscular coordination, motor coordination, motor strength, sensorimotor reflex, and learning and memory, were evaluated using standard laboratory methods. Levels of nitric oxide (NO), malondialdehyde (MDA) and activities of glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD) were evaluated in the hippocampus. Exposure of rats to noise, induced significant neurobehavioural deficits and oxidative stress while the combined administration of kaempferol and zinc gluconate significantly (P < 0.05) improved open-field performance, motor coordination, motor strength, sensorimotor reflex, and learning and memory. Co-administration of kaempferol and zinc gluconate ameliorated noise-induced oxidative stress as demonstrated by the significantly increased activities of GPx, catalase, and SOD, and decreased levels of NO and MDA (P < 0.05 and P < 0.01 respectively), compared to the DW + N group. Our results suggest that oxidative stress, evidenced by increased NO and MDA concentration and decreased activities of GPx, catalase and SOD, were involved in the molecular mechanism underlying neurobehavioural impairment in Wistar rats, exposed to noise stress. Single treatment of kaempferol exerted a more potent mitigative effect than zinc gluconate, while their combination produced an improved outcome.

Sex-Dependent Effects of Developmental Lead Exposure in Wistar Rats: Evidence from Behavioral and Molecular Correlates.

Lead (Pb) exposure in early life affects brain development resulting in cognitive and behavioral deficits. Epidemiologic and experimental evidence of sex as an effect modifier of developmental Pb exposure is emerging. In the present study, we investigated Pb effects on behavior and mechanisms of neuroplasticity in the hippocampus and potential sex differences. To this aim, dams were exposed, from one month pre-mating to offspring weaning, to Pb via drinking water at 5 mg/kg body weight per day. In the offspring of both sexes, the longitudinal assessment of motor, emotional, and cognitive end points was performed. We also evaluated the expression and synaptic distribution of N-methyl-D-Aspartate receptor (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits at post-natal day (pnd) 23 and 70 in the hippocampus. Neonatal motor patterns and explorative behavior in offspring were affected in both sexes. Pb effects in emotional response and memory retention were observed in adult females only, preceded by increased levels of GluN2A and GluA1 subunits at the post-synapse at pnd 23. These data suggest that Pb exposure during development affects glutamatergic receptors distribution at the post-synaptic spine in females. These effects may contribute to alterations in selected behavioral domains.

Polyherbal Medicine Divya Sarva-Kalp-Kwath Ameliorates Persistent Carbon Tetrachloride Induced Biochemical and Pathological Liver Impairments in Wistar Rats and in HepG2 Cells.

Divya Sarva-Kalp-Kwath (SKK) is a poly-herbal ayurvedic medicine formulated using plant extracts of Boerhavia diffusa L. (Nyctaginaceae), Phyllanthus niruri L. (Euphorbiaceae), and Solanum nigrum L. (Solanaceae), described to improve liver function and general health. In the present study, we have explored the hepatoprotective effects of SKK in ameliorating carbon tetrachloride (CCl4) induced liver toxicity using in-vitro and in-vivo test systems. Chemical analysis of SKK using Liquid Chromatography-Mass Spectroscopy (LC-MS-QToF) and High-Performance Liquid Chromatography (HPLC) revealed the presence of different bioactive plant metabolites, known to impart hepatoprotective effects. In human hepatocarcinoma (HepG2) cells, co-treatment of SKK with CCl4 effectively reduced the hepatotoxicity induced by the latter. These effects were confirmed by studying parameters such as loss of cell viability; release of hepatic injury enzymatic biomarkers- aspartate aminotransferase (AST), and alkaline phosphatase (ALP); and changes in reactive oxygen species and in mitochondrial membrane potentials. In-vivo safety analysis in Wistar rats showed no loss in animal body weight, or change in feeding habits after repeated oral dosing of SKK up to 1,000 mg/kg/day for 28 days. Also, no injury-related histopathological changes were observed in the animal's blood, liver, kidney, heart, brain, and lung. Pharmacologically, SKK played a significant role in modulating CCl4 induced hepatic injuries in the Wistar rats at a higher dose. In the 9 weeks' study, SKK (200 mg/kg) reduced the CCl4 stimulated increase in the release of enzymes (ALT, AST, and ALP), bilirubin, total cholesterol, and uric acid levels in the Wistar rats. It also reduced the CCl4 stimulated inflammatory lesions such as liver fibrosis, lymphocytic infiltration, and hyper-plasticity. In conclusion, SKK showed pharmacological effects in improving the CCl4 stimulated liver injuries in HepG2 cells and in Wistar rats. Furthermore, no adverse effects were observed up to 10× higher human equivalent dose of SKK during 28-days repeated dose exposure in Wistar rats. Based on the literature search on the identified plant metabolites, SKK was found to act in multiple ways to ameliorate CCl4 induced hepatotoxicity. Therefore, polyherbal SKK medicine has shown remarkable potentials as a possible alternative therapeutics for reducing liver toxicity induced by drugs, and other toxins.

Demyelination associated with chronic arsenic exposure in Wistar rats

Inorganic arsenic is among the major contaminants of groundwater in the world. Worldwide population-based studies demonstrate that chronic arsenic exposure is associated with poor cognitive performance among children and adults, while research in animal models confirms learning and memory deficits after arsenic exposure. The aim of this study was to investigate the long-term effects of environmentally relevant arsenic exposure in the myelination process of the prefrontal cortex (PFC) and corpus callosum (CC). A longitudinal study with repeated follow-up assessments was performed in male Wistar rats exposed to 3 ppm sodium arsenite in drinking water. Animals received the treatment from gestation until 2, 4, 6, or 12 months of postnatal age. The levels of myelin basic protein (MBP) were evaluated by immunohistochemistry/histology and immunoblotting from the PFC and CC. As plausible alterations associated with demyelination, we considered mitochondrial mass (VDAC) and two axonal damage markers: amyloid precursor protein (APP) level and phosphorylated neurofilaments. To analyze the microstructure of the CC in vivo, we acquired diffusion-weighted images at the same ages, from which we derived metrics using the tensor model. Significantly decreased levels of MBP were found in both regions together with significant increases of mitochondrial mass and slight axonal damage at 12 months in the PFC. Ultrastructural imaging demonstrated arsenic-associated decreases of white matter volume, water diffusion anisotropy, and increases in radial diffusivity. This study indicates that arsenic exposure is associated with a significant and persistent negative impact on microstructural features of white matter tracts.

RESEARCH AND EVALUATION OF THE TOXICITY PARAMETERS OF NANO-DISPERSED MAGNESIUM OXIDE IN REPEATED INHALATION EXPOSURE

A repeated inhalation exposure of Wistar rats to an aerosol of aqueous suspension of nano-dispersed magnesium oxide (5-100 nm) with actual concentration of 0,485 ± 0,121 mg/m3 has been studied. There was a significant increase in the activity of alanine aminotransferase, as well as the number of leukocytes and platelets, thrombocrit. At the same time, a significant decrease in stab neutrophils and monocytes has been noted. In animals of the experimental group, acute plethora has been found in the tissues of the brain, heart, lungs, liver, pancreas, and kidneys. Subarachnoid hemorrhages in the brain; hemorrhagic heart attacks and hyperplasia of lung tissue; hyperplasia of the myeloid germ of hematopoietic bone marrow and lymphoid tissue of the small intestine; eosinophilia of infiltrate in the stomach and large intestine have been established. The results obtained make it possible to increase the effectiveness of substantiating preventive measures for workers and population exposed to inhalation exposure to nanoparticles of magnesium oxide.

Protective Effect of Turmeric against Bisphenol-A Induced Genotoxicity in Rats.

In this study, the protective role of turmeric on genotoxic effects of Bisphenol-A exposure in Wistar rats by in vivo experiment were investigated. Bisphenol-A is a known endocrine disruptor and suspected carcinogen, that comes diet through plastics for food packaging and food processing. In this study, rats were divided into three groups of twelve animals each and were administered with Bisphenol-A by oral gavage with levels of 0, 50 and, 100 μg. Half of the animals in each group were fed with feed which contained 3% turmeric (wt/wt), for a period of 4 wk, while the rest of the rats received the same diet treatment without the addition of turmeric. At the end of the experiment, all rats were terminated and the internal organs such as liver, kidney, femurs were collected and analyzed. Mean and SD values were compared by one-way ANOVA and Kruskal-Wallis-Wilcoxon test, the formation of micronuclei was compared using Mann-Whitney U-test. Significant decrease in serum malondialdehyde and urinary 8-hydroxy-2'-deoxyguanosine levels were observed in Bisphenol-A+turmeric groups as compared to Bisphenol-A groups. Bisphenol-A groups exhibited significantly higher mean levels of DNA damage in liver and kidney as compared to the untreated control group. Bisphenol-A group showed significant increase in the formation of micronuclei which was approximately threefold higher as compared to the control group. A significant decrease in DNA migration was observed in Bisphenol-A+turmeric fed groups in liver and kidney. Turmeric feeding significantly inhibited the micronuclei formation induced by Bisphenol-A. The study results indicate that turmeric can protect against Bisphenol-A induced genotoxicity in rats.

Chronic acrolein exposure in Wistar rats: The effects of guarana extracts

Abstract Previous studies have reported that acrolein, may exert harmful effects on the brain. However, information regarding the neuroprotective properties of guarana against acrolein is not available. Due to the lack of research, we initiated the current study to investigate the effects of guarana extracts on acrolein-induced toxicity in the liver and the central nervous system of Wistar Rats. Twelve groups of 60 days old Wistar rats treated with guarana extracts (150, 250, and 350 mg/kg/day) for 8 weeks, were challenged with acrolein (2.5 mg/kg/day). Several parameters associated with oxidative damage to the brain and hepatic function, as well as behavior were evaluated. All tested concentrations of guarana extracts exerted protective effects against acrolein induced damage. No hepatic and oxidative damages or behavioral changes were observed in guarana control groups. To the best of our knowledge, this is the first study of its kind and therefore a milestone in this field.

Subchronic toxicity of cerium nitrate by 90-day oral exposure in wistar rats

This study evaluated the subchronic toxicity of cerium nitrate and determined the no observed adverse effect level (NOAEL) in Wistar rats. In accordance with the Organization for Economic Co-operation and Development guidelines, cerium nitrate was orally administered to Wistar rats by gavage at 0, 0.2, 75, 150, and 300 mg/kg bw/day for 90 days, followed by 28 days of recovery period in the 300 mg/kg bw/day and the control groups. The following parameters were evaluated: mortality, abnormalities, body weight, food consumption, hematology, serum biochemistry, urinanalysis, gross necropsy and histopathology. At the end of the treatment, several significant changes were observed in the 300 mg/kg bw/day groups: relatively decreased mean body weight of males, increased LYMPH%, RET% and decreased NEUT%, RBC of the females, increased ALT, AST and decreased ALB, T-Bil, CHO, CK, LDH of males. Significantly decreased T-Bil, CHO, CK and LDH were also observed in males of the 150 mg/kg bw/day group. Pathological examination revealed that the incidences of foreign body granulomatous lesions in lungs were higher in the 150 and 300 mg/kg bw/day groups as compared with the control group. These findings were attributed to unexpected gavage exposure because the granuloma exhibited a bronchiole-derived distribution. Taken together, the NOAEL of cerium nitrate in Wistar rats is set to be 75 mg/kg bw/day in the present study.

Expression profile of markers of oxidative stress, injury and apoptosis in anti-tuberculosis drugs induced nephrotoxicity.

Isoniazid (INH), Rifampicin (RIF) and Pyrazinamide (PZA) are part of first-line anti-tuberculosis therapy used against infection caused by Mycobacterium tuberculosis. However, these drugs are known to be potentially harmful as these are associated with numerous side effects and when taken together their harmful outcomes are elevated in a synergistic manner. Identification of possible mechanism underlying RIF + INH + PZA induced nephrotoxicity may be advantageous in developing strategies to prevent their toxic implications. In this study rats were distributed in two groups of six each: Control (tap water) and Toxicant (INH + RIF + PZA) in dosage derived through extrapolation from human dosage for 28 days once in a day. Antioxidant activity and histology of kidney were examined. In addition, apoptosis was also studied using pro and anti-apoptotic markers and TUNEL staining to check nephrotoxicity. Findings indicated that combined (INH, RIF and PZA) 28 day exposure in Wistar rats caused increase in number of free radicals/ reactive oxygen species which further cause changes in levels of enzymatic antioxidants such as glutathione, Superoxide dismutase, Catalase, and Glutathione-s-transferase. Altered content of pro (BAD&BAX) and anti-apoptotic genes (BCL-2&BCL2L1) genes, TUNEL positive cells and DNA fragmentation emphasized involvement of apoptosis. This study concluded that nephrotoxicity is accompanied during combinational anti-tuberculosis drug therapy.

The NOAEL Metformin Dose Is Ineffective against Metabolic Disruption Induced by Chronic Cadmium Exposure in Wistar Rats.

Previous studies have proposed that cadmium (Cd) is a metabolic disruptor, which is associated with insulin resistance, metabolic syndrome, and diabetes. This metal is not considered by international agencies for the study of metabolic diseases. In this study, we investigate the effect of metformin on Cd-exposed Wistar rats at a lowest-observed-adverse-effect level (LOAEL) dose (32.5 ppm) in drinking water. Metabolic complications in the rats exposed to Cd were dysglycemia, insulin resistance, dyslipidemia, dyslipoproteinemia, and imbalance in triglyceride and glycogen storage in the liver, muscle, heart, kidney, and adipose tissue. Meanwhile, rats treated orally with a No-observable-adverse-effect level (NOAEL) dose of metformin (200 mg/kg/day) showed mild improvement on serum lipids, but not on glucose tolerance; in tissues, glycogen storage was improved, but lipid storage was ineffective. In conclusion, metformin as a first-line pharmacological therapy must take into consideration the origin and duration of metabolic disruption, because in this work the NOAEL dose of metformin (200 mg/kg/day) showed a limited efficiency in the metabolic disruption caused by chronic Cd exposure.

Exploration of toxicological impacts following acute and sub-chronic exposure to ethyl anthranilate-loaded mosquito repellent patch

In the recent years, growing concern about the potential toxicity of synthetic repellents has led to the development of environmentally safe non-toxic insect control methods. Present investigation explores the toxicological impacts of ethyl anthranilate-loaded mosquito repellent patch (EAMRP) on respiratory system following acute and sub-chronic inhalation exposure in Wistar rats. Lungs parameters such as enhanced pause, tidal volume, respiration rate, inspiration time, and expiration time were determined using whole body plethysmograph. X-ray, scanning electron microscopy and histology were utilized to study the morphology and microscopical architecture of lungs. Hematological and serum biochemical markers were estimated. Cytokines such as IL-1β, IL-2, and IL-12 were also estimated in bronchoalveolar lavage fluid using ELISA kits. Finally, acute oral and dermal toxicity studies were carried out to study the accidental or intentional poisoning due to the ingestion and skin contact of EAMRP, respectively. The findings demonstrate that inhalation exposure to EAMRP did not pose any significant dose related toxicity in above mentioned experiments. Further, no appreciable toxicity was observed in both acute oral and dermal exposure. Thus, these results revealed the non toxic nature of EAMRP in preclinical studies. Hence, EAMRP can be used successfully as an alternative to existing synthetic repellents without any potential health hazards.

Spontaneous alveolar bone loss after 4NQO exposure in Wistar rats

ObjectiveThis study evaluated the effect of an experimental carcinogenic, 4-Nitroquinoline 1-oxide (4NQO), in the spontaneous alveolar bone loss (ABL) in an animal model. DesignTwenty-two male Wistar rats were included in this study. They were randomly divided into two groups: the control group (n = 10) received food and water ad libitum, and the test group (n = 12) receive the same food; however, 25 ppm of 4NQO was diluted in the drinking water. All animals were euthanized after 20 weeks, and the tongues were removed and analyzed macroscopically to determine the presence of oral mucosal lesions. All specimens were paraffin-embedded and histological sections were obtained. The microscopic analysis was based on routine procedure (haematoxylin and eosin stain). The analysis of spontaneous ABL was performed by a calibrated examiner using standardized photographs and imaging software. Differences in spontaneous ABL were assessed among the three resulting groups: control, 4NQO with oral squamous cell carcinoma (OSCC), and 4NQO without OSCC. ResultsIn the 4NQO-treated group, nine animals developed OSCC. The animals in the 4NQO with OSCC group presented significantly more spontaneous ABL (0.65 ± 0.21 mm) than the control group (0.34 ± 0.05) (p < 0.001). The animals in the 4NQO without OSCC group showed a mean spontaneous ABL of 0.47 ± 0.13 mm, which was not statistically significant different when compared to the control group (p = 0.096). ConclusionsIt was concluded that the presence of OSCC enhanced spontaneous ABL in Wistar rats when compared to control animals. Additionally, it was shown that, solely, administration of 4NQO may not be considered responsible for alveolar bone destruction.

Histomorphological Changes in the Skin and Eye Induced by Sub-Chronic Exposure of Wistar Rats to 3G Cell Phone Radiation

The effects of electromagnetic radiation produced by a 3G cell phone (third-generation) on skin tissues and eyes were investigated in terms of histomorphological parameters. A total of 26 Wistar rats (2 weeks-old, each weighing 40 g at the time of experiment) were used. They were maintained under a control room with water and food continuously available. The animals were divided into two experimental groups: Group A (Exposed) and Group B (Control), each with 13 Wistar Rats kept inside a plexi cage. Group A was exposed to a 3G cell phone radiation while Group B the control group, was not. All animals were generally anesthetized with Ketamine injection and then decapitated. The skin tissue was excised from the dorsal area and eyes samples were taken from all the rats by enucleating of the eye balls, fixed in 10% neutral buffered formalin for a minimum of 72 hours before processing through a graded alcohol and xylene was used as a clearing agent, embedded in paraffin blocks. Tissues were sectioned at 5μm thick and routinely stained with hematoxylin/eosin. Mounted slides were examined and photographed using a light microscope. Mild to severe orthokeratotic parakeratosis was observed in the skin while eye revealed loss of striation in the sclera with necrosis of the layers of rods and cones in the retina of the exposed group. We conclude that sub chronic exposure to 3G cell phone radiation impaired the protective ability of the skin and also impaired accommodation.