scholarly journals Maternal sitagliptin treatment attenuates offspring glucose metabolism and intestinal proinflammatory cytokines IL-6 and TNF-α expression in male rats

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10310
Author(s):  
Qian Zhang ◽  
Xinhua Xiao ◽  
Jia Zheng ◽  
Ming Li ◽  
Miao Yu ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Intolerance ◽  
Normal Diet ◽  
Male Rats ◽  
Male Rat ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Tnf Α ◽  
Pregnancy And Lactation ◽  
Maternal Overnutrition

Increasing evidence shows that maternal overnutrition may increase the risk of diabetes in offspring. We hypothesized that maternal sitagliptin intervention may improve glucose intolerance through gut targeting. Female Sprague-Dawley (SD) rats were fed a normal diet (ND) or a high-fat diet (HFD) for 4 weeks before mating. ND pregnant rats were divided into two subgroups: ND group (ND alone) and the ND-sitagliptin group (ND combined with 10 mg/kg/day sitagliptin treatment). HFD pregnant rats were randomized to one of two groups: HFD group (HFD alone) and the HFD-sitagliptin group (HFD combined with 10 mg/kg/day sitagliptin treatment) during pregnancy and lactation. Glucose metabolism was assessed in offspring at weaning. Intestinal gene expression levels were investigated. Maternal sitagliptin intervention moderated glucose intolerance and insulin resistance in male pups. Moreover, maternal sitagliptin treatment inhibited offspring disordered intestinal expression of proinflammatory markers, including interleukin-6 (Il6), ll1b, and tumor necrosis factor (Tnf), at weaning and reduced intestinal IL-6, TNF-α expression by immunohistochemical staining and serum IL-6, TNF-α levels. However, maternal sitagliptin intervention did not affect offspring serum anti-inflammatory cytokine IL-10 level. Our results are the first to show that maternal sitagliptin intervention moderated glucose metabolism in male offspring. It may be involved with moderating intestinal IL-6 and TNF-α expression in male rat offspring.

scholarly journals Altered Gut Microbiota and Its Metabolites in Hypertension of Developmental Origins: Exploring Differences between Fructose and Antibiotics Exposure

2021 ◽  
Vol 22 (5) ◽  
pp. 2674
Author(s):  
Chien-Ning Hsu ◽  
Julie Y. H. Chan ◽  
Kay L. H. Wu ◽  
Hong-Ren Yu ◽  
Wei-Chia Lee ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Negative Impact ◽  
Short Chain Fatty Acids ◽  
Normal Diet ◽  
Male Offspring ◽  
Sprague Dawley ◽  
Minocycline Treatment ◽  
High Fructose ◽  
Induced Hypertension ◽  
Pregnancy And Lactation

Gut microbiota-derived metabolites, in particular short chain fatty acids (SCFAs) and their receptors, are linked to hypertension. Fructose and antibiotics are commonly used worldwide, and they have a negative impact on the gut microbiota. Our previous study revealed that maternal high-fructose (HF) diet-induced hypertension in adult offspring is relevant to altered gut microbiome and its metabolites. We, therefore, intended to examine whether minocycline administration during pregnancy and lactation may further affect blood pressure (BP) programmed by maternal HF intake via mediating gut microbiota and SCFAs. Pregnant Sprague-Dawley rats received a normal diet or diet containing 60% fructose throughout pregnancy and lactation periods. Additionally, pregnant dams received minocycline (50 mg/kg/day) via oral gavage or a vehicle during pregnancy and lactation periods. Four groups of male offspring were studied (n = 8 per group): normal diet (ND), high-fructose diet (HF), normal diet + minocycline (NDM), and HF + minocycline (HFM). Male offspring were killed at 12 weeks of age. We observed that the HF diet and minocycline administration, both individually and together, causes the elevation of BP in adult male offspring, while there is no synergistic effect between them. Four groups displayed distinct enterotypes. Minocycline treatment leads to an increase in the F/B ratio, but decreased abundance of genera Lactobacillus, Ruminococcus, and Odoribacter. Additionally, minocycline treatment decreases plasma acetic acid and butyric acid levels. Hypertension programmed by maternal HF diet plus minocycline exposure is related to the increased expression of several SCFA receptors. Moreover, minocycline- and HF-induced hypertension, individually or together, is associated with the aberrant activation of the renin–angiotensin system (RAS). Conclusively, our results provide a new insight into the support of gut microbiota and its metabolite SCAFs in the developmental programming of hypertension and cast new light on the role of RAS in this process, which will help prevent hypertension programmed by maternal high-fructose and antibiotic exposure.

scholarly journals Prenatal stress induces intrauterine growth restriction and programmes glucose intolerance and feeding behaviour disturbances in the aged rat

2004 ◽  
Vol 181 (2) ◽  
pp. 291-296 ◽  
Author(s):  
J Lesage ◽  
F Del-Favero ◽  
M Leonhardt ◽  
H Louvart ◽  
S Maccari ◽  
...  
Keyword(s):  
Glucose Intolerance ◽  
Prenatal Stress ◽  
Feeding Behaviour ◽  
Maternal Stress ◽  
Plasma Corticosterone ◽  
Male Rats ◽  
Male Rat ◽  
Fasting Period ◽  
Insulin Metabolism ◽  
Foetal Growth

There is growing evidence that prenatal adversities could be implicated in foetal programming of adult chronic diseases. Since maternal stress is known to disturb the foetal glucocorticoid environment, we examined the consequences of prenatal stress on foetal growth, on glucose-insulin metabolism and on feeding behaviour in the aged male rat. In foetuses at term, maternal stress reduced body, adrenal and pancreas weight as well as plasma corticosterone and glucose levels. In aged male rats (24 months of age), prenatal stress induced hyperglycaemia and glucose intolerance and decreased basal leptin levels. Moreover, after a fasting period, they showed an increased food intake. These data suggest that maternal stress induces a long-lasting disturbance in feeding behaviour and dysfunctions related to type 2 diabetes mellitus. This programming could be linked to the early restricted foetal growth and to the adverse glucocorticoid environment in utero.

Refining the Effects Observed in a Developmental Neurobehavioral Study of Ammonium Perchlorate Administered Orally in Drinking Water to Rats. II. Behavioral and Neurodevelopment Effects

2005 ◽  
Vol 24 (6) ◽  
pp. 451-467 ◽  
Author(s):  
Raymond G. York ◽  
John Barnett ◽  
Michael F. Girard ◽  
David R. Mattie ◽  
Marni V. K. Bekkedal ◽  
...  
Keyword(s):  
Drinking Water ◽  
Ammonium Perchlorate ◽  
Brain Regions ◽  
Male Rats ◽  
Male Rat ◽  
Sprague Dawley ◽  
Continuous Access ◽  
Brain Morphometry ◽  
The Central Nervous System ◽  
The Right

A developmental neurotoxicity study was conducted to generate additional data on the potential functional and morphological hazard to the central nervous system caused by ammonium perchlorate in offspring from in utero and lactation exposure. Female Sprague-Dawley rats (23 to 25/group) were given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 10.0 mg/kg-day perchlorate in the drinking water beginning 2 weeks prior to mating and continuing through day 10 of lactation for the behavioral function assessment or given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 30.0 mg/kg-day beginning on gestation day 0 and continuing through day 10 of lactation for neurodevelopment assessments. Motor activity was conducted on postpartum days 14, 18, and 22 and juvenile brain weights, neurohistopathological examinations, and regional brain morphometry were conducted on postpartum days 10 and 22. This research revealed a sexually dimorphic response, with some brain regions being larger in perchlorate-treated male rats than in comparable controls. Even so, there was no evidence of any obvious exposure-related effects on male rat brain weights or neuropathology. The most consistent exposure-related effect in the male pups was on the thickness of the corpus callosum, with both the right- and left-sided measures of the thickness of this white matter tract being significantly greater for the male pups in the 0.1 and 1.0 mg/kg-day exposure groups. The behavioral testing suggests prenatal exposure to ammonium perchlorate does not affect the development of gross motor movements in the pups.

TNF-α enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats

2002 ◽  
Vol 283 (1) ◽  
pp. R130-R143 ◽  
Author(s):  
Jena B. Giardina ◽  
Gachavis M. Green ◽  
Kathy L. Cockrell ◽  
Joey P. Granger ◽  
Raouf A. Khalil
Keyword(s):  
Vascular Reactivity ◽  
Pregnancy Induced Hypertension ◽  
Vascular Relaxation ◽  
Sprague Dawley ◽  
Direct Role ◽  
Pregnant Rats ◽  
No Donor ◽  
Vascular Contraction ◽  
Tnf Α ◽  
Induced Hypertension

Tumor necrosis factor-α (TNF-α) is elevated in the plasma of preeclamptic women and may have a role in pregnancy-induced hypertension. However, whether the hemodynamic effects of TNF-α reflect the direct effects on vascular reactivity is unclear. We tested the hypothesis that TNF-α impairs endothelium-dependent relaxation and enhances vascular contraction in systemic vessels of pregnant rats. We measured isometric contraction in aortic strips isolated from virgin and pregnant Sprague-Dawley rats (nontreated vs. treated for 2 h with 10–1,000 pg/ml TNF-α). In endothelium-intact vascular strips, TNF-α caused greater enhancement of phenylephrine (Phe) contraction in pregnant than virgin rats. TNF-α caused significant inhibition of ACh- and bradykinin-induced vascular relaxation and nitrite/nitrate production that were more prominent in pregnant than virgin rats. N G-nitro-l-arginine methyl ester [l-NAME, 100 μM, an inhibitor of nitric oxide (NO) synthase] or 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (ODQ, 1 μM, an inhibitor of cGMP production in smooth muscle) inhibited ACh relaxation and enhanced Phe contraction in nontreated but to a lesser extent in TNF-α-treated vessels, particularly those of pregnant rats. Endothelium removal enhanced Phe contraction in nontreated but not TNF-α-treated vessels, especially those of pregnant rats. Relaxation of Phe contraction with the NO donor sodium nitroprusside was not different between nontreated and TNF-α-treated vessels. Thus TNF-α enhances vascular contraction and inhibits endothelium-dependent NO-cGMP-mediated vascular relaxation in systemic vessels, particularly those of pregnant rats. The results support a direct role for TNF-α as a possible mediator of increased vascular resistance associated with pregnancy-induced hypertension.

scholarly journals Pregnant rats treated with a high-fat/prooxidant Western diet with ANG II and TNF-α are resistant to elevations in blood pressure and renal oxidative stress

2015 ◽  
Vol 308 (11) ◽  
pp. R945-R956 ◽  
Author(s):  
Mark W. Cunningham ◽  
Crystal A. West ◽  
Xuerong Wen ◽  
Aihua Deng ◽  
Chris Baylis
Keyword(s):  
Oxidative Stress ◽  
Western Diet ◽  
Kidney Cortex ◽  
Ang Ii ◽  
Sprague Dawley ◽  
High Fat ◽  
Redox Systems ◽  
Plasma Protein Concentration ◽  
Pregnant Rats ◽  
Tnf Α

Oxidative stress and inflammation are risk factors for hypertension in pregnancy. Here, we examined the 24-h mean arterial pressure (MAP) via telemetry and the nitric oxide (NO) and redox systems in the kidney cortex, medulla, and aorta of virgin and pregnant rats treated with a high-fat/prooxidant Western diet (HFD), ANG II, and TNF-α. Female Sprague-Dawley rats were given a normal diet (ND) or a HFD for 8 wk before mating. Day 6 of pregnancy and age-matched virgins were implanted with minipumps infusing saline or ANG II (150 ng·kg−1·min−1) + TNF-α (75 ng/day) for 14 days. Groups consisted of Virgin + ND + Saline (V+ND) ( n = 7), Virgin + HFD +ANG II and TNF-α (V+HFD) ( n = 7), Pregnant + ND + Saline (P+ND) ( n = 6), and Pregnant + HFD + ANG II and TNF-α (P+HFD) ( n = 8). After day 6 of minipump implantation, V+HFD rats displayed an increase in MAP on days 7, 8, and 10–15 vs. V+ND rats. P+HFD rats, after day 6 of minipump implantation, showed an increase in MAP only on day 7 vs. P+ND rats. P+HFD rats had a normal fall in 24-h MAP, hematocrit, plasma protein concentration, and osmolality at late pregnancy. No change in kidney cortex, medulla, or aortic oxidative stress in P+HFD rats. P+HFD rats displayed a decrease in nNOSβ abundance, but no change in kidney cortex NOxcontent vs. P+ND rats. Pregnant rats subjected to a chronic HFD and prooxidant and proinflammatory insults have a blunted increase in 24-h MAP and renal oxidative stress. Our data suggest renal NO bioavailability is not altered in pregnant rats treated with a HFD, ANG II, and TNF-α.

Biochemical changes and oxidative stress induced by zearalenone in the liver of pregnant rats

2014 ◽  
Vol 34 (1) ◽  
pp. 65-73 ◽  
Author(s):  
C Zhou ◽  
Y Zhang ◽  
S Yin ◽  
Z Jia ◽  
A Shan
Keyword(s):  
Oxidative Stress ◽  
Messenger Rna ◽  
Experimental Period ◽  
Normal Diet ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Sprague Dawley Rats ◽  
Albumin Content ◽  
Dose Dependent

The aim of the present research was to examine the toxic influence of different doses of zearalenone (ZEN) on the liver, especially oxidative stress induced by ZEN on the liver. A total of 48 pregnant Sprague-Dawley rats were randomly assigned into 4 treatments groups with 12 animals in each. The rats were fed with a normal diet treated with 0 mg/kg (control), 50 mg/kg (treatment 1), 100 mg/kg (treatment 2), or 150 mg/kg (treatment 3) ZEN in feed on gestation days (GDs) 0–7 and then all the rats were fed with a normal diet on GDs 8–20. The experimental period lasted 21 days. The results showed that exposure to ZEN induced increase in aspartate amino transferase, alanine aminotransferase, and alkaline phosphatase activities and decrease in total protein and albumin content in a dose-dependent manner and also induce decrease in superoxide dismutase and glutathione peroxidase activities and increase in malondialdehyde content in a dose-dependent manner in the serum and the liver. The increased transcription of cytochrome P450 2E1 (CYP2E1) was detected in the liver after exposure to ZEN. These results suggested that ZEN not only caused damage in the liver of pregnant rats in a dose-dependent manner but also induced the messenger RNA expression of CYP2E1 in the liver.

scholarly journals Sex-, tissue-, and exposure duration-dependent effects of imidacloprid modulated by piperonyl butoxide and menadione in rats. Part I: oxidative and neurotoxic potentials

2014 ◽  
Vol 65 (4) ◽  
pp. 387-398 ◽  
Author(s):  
Mustafa Yardimci ◽  
Yusuf Sevgiler ◽  
Eyyup Rencuzogullari ◽  
Mehmet Arslan ◽  
Mehmet Buyukleyla ◽  
...  
Keyword(s):  
Cholinesterase Activity ◽  
Specific Effect ◽  
Piperonyl Butoxide ◽  
Female Rats ◽  
Male Rats ◽  
Male Rat ◽  
Total Protein Content ◽  
Sprague Dawley ◽  
Adverse Action ◽  
Liver And Kidney

Abstract Earlier research has evidenced the oxidative and neurotoxic potential of imidacloprid, a neonicotinoid insecticide, in different animal species. The primary aim of this study was to determine how metabolic modulators piperonyl butoxide and menadione affect imidacloprid’s adverse action in the liver and kidney of Sprague-Dawley rats of both sexes. The animals were exposed to imidacloprid alone (170 mg kg-1) or in combination with piperonyl butoxide (100 mg kg-1) or menadione (25 mg kg-1) for 12 and 24 h. Their liver and kidney homogenates were analysed spectrophotometrically for glutathione peroxidase, glutathione S-transferase, catalase, total cholinesterase specific activities, total glutathione, total protein content, and lipid peroxidation levels. Imidacloprid displayed its prooxidative and neurotoxic effects predominantly in the kidney of male rats after 24 h of exposure. Our findings suggest that the observed differences in prooxidative and neurotoxic potential of imidacloprid could be related to differences in its metabolism between the sexes. Co-exposure (90-min pre-treatment) with piperonyl butoxide or menadione revealed tissue-specific effect of imidacloprid on total cholinesterase activity. Increased cholinesterase activity in the kidney could be an adaptive response to imidacloprid-induced oxidative stress. In the male rat liver, co-exposure with piperonyl butoxide or menadione exacerbated imidacloprid toxicity. In female rats, imidacloprid+menadione co-exposure caused prooxidative effects, while no such effects were observed with imidacloprid alone or menadione alone. In conclusion, sex-, tissue-, and duration-specific effects of imidacloprid are remarkable points in its toxicity

The Effects of Jp-8 Jet Fuel on Male Sprague-Dawley Rats after a 90-Day Exposure By Oral Gavage

1995 ◽  
Vol 11 (4) ◽  
pp. 423-435 ◽  
Author(s):  
David R. Mattie ◽  
Gary B. Marit ◽  
Carlyle D. Flemming ◽  
James R. Cooper
Keyword(s):  
Adverse Effects ◽  
Jet Fuel ◽  
Additional Treatment ◽  
Male Rats ◽  
Male Rat ◽  
Oral Exposure ◽  
Sprague Dawley ◽  
Weight Changes ◽  
Inhalation Study ◽  
Dose Dependent

The U.S. Air Force is converting from JP-4 jet fuel to the less volatile JP-8 jet fuel, which is similar to commercial Jet Fuel A. Our previous 90-day inhalation study with JP-8 vapor, using F-344 rats and C57BL/6 mice, resulted in no treatment-related adverse effects other than α 2-microglobin nephropathy in male rats (Mattie et al., 1991). In the present study, male rats were dosed with neat JP-8 (0, 750, 1500, 3000 mg/kg) daily by gavage for 90 days in an effort to characterize the kidney lesion and assess further any additional adverse effects associated with prolonged oral exposure to this fuel. Results of this study revealed a significant dose-dependent decrease in body weights of rats exposed to JP-8. Male rat-specific α 2-microglobin nephropathy was observed by histopathologic examination. A number of significant changes were also seen in blood and urine that were not dose-dependent. Additional treatment-related effects were a gastritis and a perianal dermatitis. Although there were no histopathological or weight changes in the livers of exposed rats, there was an increase in the liver enzymes AST and ALT. The elevated enzymes did not increase with increasing dose of JP-8.

scholarly journals Orlistat reverses intratesticular lactate transport decline and infertility in male obese rats

Reproduction ◽  
2020 ◽  
Vol 160 (6) ◽  
pp. 863-872 ◽  
Author(s):  
Joseph Bagi Suleiman ◽  
Victor Udo Nna ◽  
Zaida Zakaria ◽  
Zaidatul Akmal Othman ◽  
Ainul Bahiyah Abu Bakar ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Glucose Metabolism ◽  
Sexual Behaviour ◽  
Mating Behaviour ◽  
Male Rats ◽  
Cgmp Level ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Obese Rats ◽  
Fertility Potential

Obesity and its accompanying complications predispose to abnormal testicular glucose metabolism, penile erectile dysfunction and subfertility. This study examined the potentials of orlistat in attenuating erectile dysfunction and fertility decline in high-fat diet (HFD)-induced obesity in male rats. Eighteen adult male Sprague–Dawley rats whose weights were between 250 and 300 g were divided into three groups (n = 6/group) namely: normal control (NC), HFD and HFD + orlistat (10 mg/kg body weight/day co-administered for 12 weeks) (HFD+O). During the 11th and 12th week, mating behaviour and fertility parameters were evaluated, and parameters of glucose metabolism were assessed at the end of the 12th week. Orlistat increased testicular mRNA levels of glucose transporters (Glut1 and Glut3), monocarboxylate transporters (Mct2 and Mct4) and lactate dehydrogenase type C (Ldhc), decreased intratesticular lactate and glucose levels, and LDH activity in obese rats. Furthermore, orlistat increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) activities, and total antioxidant capacity (TAC), but decreased malondialdehyde level in the penis of obese rats. Similarly, orlistat improved penile cGMP level, sexual behaviour and fertility outcome in obese rats. Penile cGMP level correlated positively with total mounts and intromissions but correlated negatively with mount/intromission ratio. Orlistat improves fertility potential in obese state by targeting testicular lactate metabolism, penile oxidative stress and sexual behaviour in rats. Therefore, orlistat shows a promising protective effect and may preserve the fertility potential of obese men.

scholarly journals The Effect of Soy Milk on Mounting Latency, Mounting Frequency, and Reproductive Development in Male Wistar Rats (Rattus Norvegicus)

2021 ◽  
Vol 9 (B) ◽  
pp. 670-678
Author(s):  
Nurdiana Nurdiana ◽  
Pradnyawati Chania ◽  
Rifzi Nurvitasari ◽  
Azmiatun Nisa ◽  
Styan Wahyu Diana ◽  
...  
Keyword(s):  
Rattus Norvegicus ◽  
Wistar Rats ◽  
Reproductive Development ◽  
Normal Diet ◽  
Male Rats ◽  
Male Rat ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Soy Milk ◽  
Male Wistar Rats

AIM: This research aims to examine the effects of soy milk on mounting latency (ML), mounting frequency (MF), estrogen levels, androgen-binding protein (ABP) expression, and spermatogenesis in male rats (Rattus norvegicus). METHODS: Twenty-four male wistar rats (Rattus norvegicus) aged 4 weeks were divided into four groups. Control group (given a normal diet), P1; P2; P3 (given the normal diet and soy milk powder at doses of 7.1; 14.2; 21.3 g/KgBW/day, respectively) for 6 weeks. Observation of ML and MF were performed at 9 weeks 5 days of age, and rat surgery was performed at 10 weeks of age. Analysis of estrogen hormone levels was conducted by enzyme-linked immunosorbent assay (ELISA), ABP staining was using immunohistochemistry method, testicular spermatogenesis was observed using histopathological methods, and observation of spermatozoa was performed under the microscope.  RESULTS: The results showed no significant reduction of ML and MF, estrogen levels, and ABP expression (p ≤ 0.256; 0.865; 0.959, respectively) in male rat, but there was a significant decrease in the number, morphology, motility of spermatozoa, and testicular histophatology, (p ≤ 0.000, 0.003, 0.008, 0.000, respectively). CONCLUSION: The administrassion of soy milk in various doses (7.1;14.2;21.3 g/KgBW/day) in male Wistar rats (Rattus norvegicus) had showed significantly difference on histopathological evaluation using Johnson’s scoring system, sperm quantity and quality, while on mounting latency and frequency, estrogen levels, and ABP expressions did not show significantly difference between groups. That describe of isoflavone in soy milk can affect several aspects related to male endocrine and reproductive development.

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