Genotoxicity Evaluation in Severe or Mild Diabetic Pregnancy in Laboratory Animals

AbstractThis study aimed to evaluate the genotoxicity (DNA damage levels) in lymphocyte samples from pregnant Wistar rats with severe or mild diabetes and in whole blood samples from their newborns. Wistar female rats (1 and 90 days of age) and male rats (approximately 90 days of age) were used. The experiment consisted of 2 experimental groups (n=8 animals/group): 1) rats with severe diabetes, 2) rats with mild diabetes. For mild diabetes induction, the rats received streptozotocin (STZ) subcutaneously (100 mg/kg body weight) at day of birth, and those showing glycemia from 120 to 300 mg/dL in their adult life were included. For induction of severe diabetes, adult rats received 40 mg/kg STZ (intravenous route), and those showing glycemia > 300 mg/dL were included. At day 21 of pregnancy, the rats were anesthetized and euthanized for removal of maternal and fetal blood samples for determination of the oxidative DNA damage by applying Endo III and Fpg using the comet assay. Thus, the rats with mild diabetes and their offspring showed higher Fpg-sensitive sites, reflecting the damage resulting from hyperglycemia. The rats with severe diabetes and their offspring showed higher oxidative DNA damage detected by Fpg and Endo III-sensitive sites, showing general repercussions related to diabetes. The enzymatic treatment for DNA damage evidenced that the maternal repercussions of diabetes are associated with oxidative DNA damage of their newborn, which was not reflected using only the analysis of DNA damage free of the enzymes.

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Toxicological evaluation of hydroethanol leaf extract of Pupalia lappacea (Linn.) Juss. (Amaranthaceae) in rodents

Drug Metabolism and Personalized Therapy ◽

10.1515/dmdi-2021-0115 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Murtala Akanji Abdullahi ◽

Elijah Oladapo Oyinloye ◽

Akinyinka Alabi ◽

Aderonke Adeyinka Aderinola ◽

Luqman Opeyemi Ogunjimi ◽

...

Keyword(s):

Leaf Extract ◽

Density Lipoprotein ◽

Serum Testosterone ◽

Female Rats ◽

Male Rats ◽

Laboratory Animals ◽

Serum Testosterone Level ◽

Control Group ◽

Toxicological Evaluation ◽

Liver And Kidney

Abstract Objectives Several studies have established the ethnobotanical benefits of Pupalia lappacea (PL) in laboratory animals without extensive toxicological evaluation of its safety profiles. Thus, an extensive toxicological investigation of sub-chronic oral administration of the hydroethanol leaf extract of P. lappacea in rodents was carried out in this study. Methods Different groups of rats were treated orally with the extract (10, 50 and 250 mg/kg) daily for 90 consecutive days. The control group received distilled water (10 mL/kg). After 90 days, some rats were left for additional 30 days without treatment for reversibility study. Blood and organs samples were collected for different evaluations at the end of study periods. Results The extract decreased the bodyweights, feeding and water intakes in female rats. PL increased the weights of the liver and kidney in male rats. PL increased the red blood cell (RBC), packed cell volume (PCV), hemoglobin (Hb), triglycerides (TRIG), cholesterol and high density lipoprotein (HDL) contents in rats. PL (250 mg/kg) significantly reduced the sperm motility and serum testosterone level. Cyto-architectural distortions of the testes, liver and spleen were visible. Conclusions The findings showed that P. lappacea is relatively safe at lower doses but cautions should be taken at higher dose.

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Amelioration of fenitrothion induced oxidative DNA damage and inactivation of caspase-3 in the brain and spleen tissues of male rats by N-acetylcysteine

Life Sciences ◽

10.1016/j.lfs.2019.06.009 ◽

2019 ◽

Vol 231 ◽

pp. 116534 ◽

Cited By ~ 8

Author(s):

Rasha T. Alam ◽

Tamer S. Imam ◽

Azza M.A. Abo-Elmaaty ◽

Ahmed Hamed Arisha

Keyword(s):

Dna Damage ◽

Oxidative Dna Damage ◽

Caspase 3 ◽

Male Rats ◽

The Brain

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Abstract 269: Cardiac Aging in Rats: Do Female and Male Hearts Age Differently?

Circulation Research ◽

10.1161/res.111.suppl_1.a269 ◽

2012 ◽

Vol 111 (suppl_1) ◽

Author(s):

Eduard I Dedkov ◽

Alessandro Pingitore

Keyword(s):

Experimental Studies ◽

Left Ventricular ◽

Female Rats ◽

Male Rats ◽

Laboratory Animals ◽

Cardiac Aging ◽

Male And Female ◽

Male And Female Rats ◽

Significant Difference ◽

Systolic Performance

Background: In recent years, the use of middle-aged and old animals of both sexes has become preferential in experimental studies involving the models of cardiovascular diseases to better reflect a human population. However, the evidence showing the extent of sex-related differences in cardiac aging of laboratory animals remains obscure. Accordingly, we designed our study to determine whether the male and female rats differ during aging with regard to left ventricular (LV) geometry and systolic function. Methods: We performed transthoracic echocardiographic examinations in 12-month-old (12mo) and 24 month-old (24mo) male and female Sprague-Dawley rats (Charles River, Wilmington, MA) under 1.5% isoflurane anesthesia using a linear (Matrix) array transducer probe GE M12L (5.5-14.0 MHz) and a GE Vivid 7 Dimension ultrasound system. Two-dimensional short-axis views and M-mode tracings of the LV at the papillary muscle level were recorded and used to estimate various LV parameters. Results: We found that 24mo-Female rats had a significant increase in LV chamber dimensions associated with a reduction in its systolic performance as compared to 12mo-Female rats (Table 1). In contrast, LV parameters remained similar between 12mo- and 24mo-Male rats. Table 1. Echocardiographic parameters of LV chamber geometry and systolic performance Values are means ± SE. Arrow indicates a significant difference between age groups ( P ≤ 0.05). Conclusion: Our data demonstrate that during cardiac aging female rats have a different pattern of LV changes compared to males that must be considered in the design of future experimental studies.

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Developmental increases in plasma leptin binding activity and tissue Ob-Re mRNA expression in the rat

Journal of Endocrinology ◽

10.1677/joe.1.06045 ◽

2005 ◽

Vol 184 (3) ◽

pp. 535-541 ◽

Cited By ~ 10

Author(s):

Jeremy T Smith ◽

Peter J Mark ◽

Brendan J Waddell

Keyword(s):

Mrna Expression ◽

Adult Life ◽

Tissue Expression ◽

Binding Activity ◽

Female Rats ◽

Male Rats ◽

Target Cells ◽

Male And Female Rats ◽

Age Related ◽

Plasma Leptin

Leptin’s actions are mediated via the long form of its receptor, Ob-Rb, but access to this receptor on target cells is also influenced by truncated leptin receptor isoforms Ob-Ra and Ob-Re. Plasma leptin binding activity is primarily attributed to Ob-Re, which can restrict leptin passage to extravascular tissue. In this study we investigated whether plasma leptin binding activity changes from fetal to adult life in male and female rats, and whether tissue expression of Ob-Re mRNA changes during development. Plasma leptin binding activity was low in the fetus and prepubertal rats but then increased in male rats by more than three-fold from pre- to post-puberty and by a further two-fold by 7 months of age. A more modest increase in plasma leptin binding activity was observed in females such that a clear sex difference became evident after puberty. There was also a reduction in hypothalamic Ob-Rb protein content between puberty and adult life in female rats. Combined with the higher levels of plasma leptin binding activity, this change in hypothalamic Ob-Rb expression is likely to lead to a more leptin-resistant state in aging females. To assess possible sources of circulating leptin binding activity, Ob-Re mRNA expression was measured by quantitative RT-PCR in several tissues from male rats soon after puberty and at 7 months of age. All tissues examined (testis, epididymis, adrenal, liver, adipose and spleen) expressed Ob-Re mRNA, and there was a dramatic, age-related increase in expression (> 300-fold) in the spleen. These data show that, in addition to the developmental increase in hypothalamic Ob-Rb expression previously reported, plasma leptin binding activity increases several fold from fetal to adult life in the rat. This suggests that the actions of leptin depend not only on its synthesis in adipose tissue and Ob-Rb expression in target cells, but also on factors that regulate tissue expression of Ob-Re and thus leptin transport within plasma.

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Determination of pre and post treatment oxidative status and oxidative DNA damage in diarrheic calves

Indian Journal of Animal Research ◽

10.18805/ijar.7046 ◽

2015 ◽

Vol 49 (6) ◽

Author(s):

Mustafa Kabu ◽

Ibrahim Hakki Cigerci ◽

Cangir Uyarlar ◽

Haci Ahmet Celik

Keyword(s):

Dna Damage ◽

Body Temperature ◽

Dry Matter ◽

Oxidative Dna Damage ◽

High Energy ◽

Oxidative Status ◽

Blood Samples ◽

Damage Level ◽

Before And After ◽

Diarrheic Calves

Increase in production of free radicals causes damage in lipids of cell membrane, weakening in functions of cell proteins and DNA damage. The aim of the present study was to determine the oxidative status, level of oxidative DNA damage and treatment effectiveness on these parameters on diarrheic calves. The study was conducted using 10 clinically holstein calves from 2-3 months of age. Antidiarrheic treatment containing Amonium sulphate (30mg/kg/day, Gabbrocol, Ceva Inc.), a mixture of Bismuth subcarbonate, kaolin, pectin (10g/day, Bismol, Bioteknik Inc.), vitamin and mineral mixture (105g/day, Sky High Energy, Egevet Co.Ltd) as drugs orally administered to all calves for 3 days. Body temperature, feces and blood samples were taken before and after treatment. Dry matter measured (%) in feces, DNA damage level and some hematologic parameters, total oxidant status (TOS), total antioxidant status (TAS) and some biochemical parameters were measured from blood samples. HB, ALT, TP levels did not differ before and after treatment. However, body temperature (p<0.01), WBC (p<0.01), HCT (p<0.05), GGT (p<0.01), TOS (p<0.05), DNA damage (p<0.05) were decreased, dry matter in feces (p<0.01), RBC (p<0.05), AST (p<0.01), Albumin (p<0.01) and TAS (p<0.05) were increased after treatment. The results of the study indicate that oxidative DNA damage increases with degenerative diseases such as diarrhea and decreases to the normal range after effective treatment. It can be suggested from these results that oxidative DNA damage might be a good indicator to reveal the degeneration level of diarrhea in animals and a good parameter to evaluate the effectiveness of the treatment in terms of cellular form.

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Late Effect of Early Hypoxic Disturbance in the Rat Heart: Gender Differences

Physiological Research ◽

10.33549/physiolres.931833 ◽

2010 ◽

pp. 127-131

Author(s):

I Netuka ◽

O Szárszoi ◽

J Malý ◽

H Říha ◽

D Turek ◽

...

Keyword(s):

Adult Life ◽

Female Rats ◽

Male Rats ◽

Late Effect ◽

Hypoxic Exposure ◽

Acute Ischemia ◽

Long Term Effects ◽

Male And Female Rats ◽

Perfused Hearts

Perinatal hypoxemia may have serious long-term effects on the adult cardiovascular system and may lead to sex-dependent changes in cardiac tolerance to acute ischemia in adult life. The aim of the study was to answer the question whether gonadectomy of the male and female rats in the early phase of ontogenetic development affects the late effect of perinatal hypoxia. Pregnant Wistar rats were placed into a normobaric hypoxic chamber (12 % O2) 7 days before the expected date of delivery. Newborn pups were kept in the chamber with their mothers for another 5 days after birth. After hypoxic exposure all animals were kept for 3 months in room air. Some of the pups were gonadectomized right after removal from the hypoxic chamber. Ventricular arrhythmias were assessed on isolated perfused hearts. Castration did not influence arrhythmogenesis in the adult normoxic or perinatally hypoxic female hearts. Nevertheless, the number of arrhythmias was decreased in perinatally hypoxic gonadectomized males. In conclusion, we have shown that perinatal normobaric hypoxia increased cardiac tolerance to acute ischemia in adult male rats; however, it had no late effect in females. Gonadectomy did not affect arrhythmogenesis in both normoxic and hypoxic female hearts, whereas in males significantly decreased the number of arrhythmias.

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Determination of acute toxicity parameters of “Zoodizin” disinfectant

Ukrainian Journal of Veterinary and Agricultural Sciences ◽

10.32718/ujvas2-2.09 ◽

2019 ◽

Vol 2 (2) ◽

pp. 41-44

Author(s):

O. L. Nechyporenko ◽

A. V. Berezovskyy ◽

H. A. Fotina ◽

R. V. Petrov ◽

T. I. Fotina

Keyword(s):

Body Weight ◽

Acute Toxicity ◽

Oral Administration ◽

White Male ◽

Lethal Dose ◽

Well Being ◽

Female Rats ◽

Male Rats ◽

Laboratory Animals ◽

Intragastric Administration

An important element in ensuring the epizootic well-being of the poultry industry is disinfection. Modern poultry farming requires a large number of effective disinfectants. It is known that the resistance of microorganisms to the effects of disinfectants is based on a genotypic mechanism. The nature of the formation of resistance to disinfectants and antiseptics is different than antibiotics. With regard to disinfectants, resistance is formed more slowly and the proportion of resistant strains in the population of microorganisms may not be high for a long time. This is due to different mechanisms of formation of resistance to antibiotics and disinfectants, in the first case – plasmid mechanism, in the second – chromosomal. However, increasing the resistance to the active substance in disinfectants can be widespread, so it is necessary to periodically rotate disinfectants. The goal of the work – to investigate the parameters of acute toxicity of the disinfectant biocide “Zodizin”. The studies were conducted in the laboratory of Veterinary Pharmacy and the Vivarium of Sumy National Agrarian University. The drug “Zodizine” contains: polyhexamethyleneguanidine hydrochloride – 21.0 %, alkylldimethylbenzylammonium chloride – 3.0 %. For toxicological examination of the disinfectant, healthy white male rats and white female rats weighing 200 ± 10 g 1.5 years of age were used. In the study of acute toxicity of animals observed daily, noted the general condition of the animals, features of their behavior. Studies have found that the toxic effect of the disinfectant “Zodizin” clinically manifested almost equally in both males and females. The average lethal dose for the rat female was 1000.0 ± 35.0 mg/kg body weight, males 1033.0 ± 34.3 mg/kg. Therefore, according to the classification of substances by toxicity, the drug by intragastric administration can be attributed to low-toxic substances. Observations on animals revealed that 1–3 hours after oral administration of the drug in a subtoxic dose in laboratory animals, shortness of breath and inhibition of the central nervous system were noted. Most of them died during the first day. Subsequent observations of the surviving animals indicated that their motor response was suppressed over the next 24–72 hours. Conclusions and prospects for further research: 1. It was found that the average lethal dose of the drug “Zodizin” with oral administration to rats-females was 1000.0 ± 35.0 mg/kg body weight, males – 1033.0 ± 34.3 mg/kg. 2. Experimental studies have proved that the disinfectant “Zodizin” according to GOST 12.1.007-76, belongs to the IV class of danger, that is, to the low-dangerous compounds, and according to GOST 12.1.07 – to the III class of hazard of substances and can be used for disinfection premises where animals and poultry are kept. Further, the sporoсide and corrosion properties of the “Zoodizin” biocide will be studied.

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Prenatal cytokine exposure results in obesity and gender-specific programming

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2001.281.2.e326 ◽

2001 ◽

Vol 281 (2) ◽

pp. E326-E334 ◽

Cited By ~ 96

Author(s):

Jovanna Dahlgren ◽

Cecilia Nilsson ◽

Eva Jennische ◽

Hoi-Por Ho ◽

Elias Eriksson ◽

...

Keyword(s):

Locomotor Activity ◽

Prenatal Exposure ◽

Adult Life ◽

Female Rats ◽

Male Rats ◽

Plasma Testosterone ◽

Adult Age ◽

Fat Depots ◽

Tnf Α ◽

Gender Specific

Prenatal events appear to program hormonal homeostasis, contributing to the development of somatic disorders at an adult age. The aim of this study was to examine whether maternal exposure to cytokines or to dexamethasone (Dxm) would be followed by hormonal consequences in the offspring at adult age. Pregnant rats were injected on days 8, 10, and 12 of gestation with either human interleukin-6 (IL-6) or tumor necrosis factor-α (TNF-α) or with Dxm. Control dams were injected with vehicle. All exposed offspring developed increased body weight ( P < 0.05–0.001), apparently due to an increase of 30–40% in adipose tissue weight ( P < 0.05–0.01). Corticosterone response to stress was increased in the IL-6 group ( P < 0.05–0.01). Dxm-treated male rats exhibited blunted Dexamethasone suppression test results. In male rats, insulin sensitivity was decreased after IL-6 exposure ( P < 0.01), whereas basal insulin was elevated in the TNF-α group ( P < 0.01). In female rats, plasma testosterone levels were higher in all exposed groups compared with controls ( P < 0.01–0.001), with the exception of Dxm-exposed offspring. Males in the TNF-α group showed decreased locomotor activity ( P < 0.05), and females in the IL-6 group showed increased locomotor activity ( P < 0.05). These results indicate that prenatal exposure to cytokines or Dxm leads to increased fat depots in both genders. In females, cytokine exposure was followed by a state of hyperandrogenicity. The results suggest that prenatal exposure to cytokines or Dxm can induce gender-specific programming of neuroendocrine regulation with consequences in adult life.

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