Dynamics of blood glucose changes and hormonal sensitivity under anesthesia with medetomidine-midazolam-butorphanol anesthesia in rats.

Inverse salt sensitivity, an increase in blood pressure (BP) when sodium intake is reduced, affects about 10-15% of the population, yet the mechanisms underlying this alteration in BP are not well understood. The renal dopamine D2 receptor (D2R) plays a critical role in maintaining normal BP and preventing inflammation and tissue injury. The DRD2 is highly polymorphic, and single nucleotide polymorphisms (SNPs) in this gene impair DRD2 synthesis and stability. Specifically, rs6277 SNP in exon 7 of DRD2 is associated with decreased D2R expression and is present in some individuals with hypertension. We have reported that human renal proximal tubular cells with this SNP have decreased D2R mRNA and protein expressions and increased renal Na+ pump/transporter expression. To study the effects of rs6277 on sodium balance and BP, using CRISPR-Cas9, we generated C57Bl/6 mice lacking their own Drd2 but instead express either the human DRD2 wild-type ( DRD2 WT) or rs6277 ( DRD2 Mut). Male and female mice were placed for one week on three distinct salt diets: normal salt (NS; 0.4% NaCl), high salt (HS; 4% NaCl), and low salt (LS; less than 0.08% NaCl) diets. On NS diet, BPs (measured by tail-cuff plethysmography under pentobarbital anesthesia) were slightly higher in male DRD2 Mut than DRD2 WT mice (79±3 vs 73±±0.5 mm Hg; P<0.04; n=5-7/group) while BPs were similar in female DRD2 Mut and DRD2 WT mice (77±3 vs 75±3 mm Hg: n=8/group). On HS diet, BPs were similar in DRD2 WT and DRD2 Mut mice (males 89±2 vs 92±3; females 79±3 vs 87±5 mm Hg). However, on LS diet DRD2 Mut had higher BPs than DRD2 WT mice (males: 72±2 vs 90±2 P<0.001; females: 68±1 vs 88±3 mm Hg, P<0.001). Thus, in DRD2 WT mice, BP increased on HS diet and decreased on LS, while in DRD2 Mut mice, BP increased on both LS and HS diets. There were no significant differences in urinary sodium excretion between DRD2 WT and DRD2 Mut male and female mice on the different diets. These findings suggest that alterations in DRD2 expression/function may be the underlying cause of inverse salt sensitivity of BP because the presence of DRD2 rs6277 is associated with inverse salt sensitivity in mice and humans. Moreover, the increased BP in DRD2 rs6277 mice on LS is independent of urinary sodium excretion.

Septic cardiomyopathy (SCM) is a prevalent and severe complication associated with sepsis. This study explores the effects of sevoflurane and pentobarbital on lipopolysaccharide (LPS) -induced SCM and elucidates underlying mechanisms. The SCM model was established using an intraperitoneal injection of 10mg/kg LPS. Pentobarbital and sevoflurane were administered thirty minutes post-model establishment. Following the echocardiographic assessment, mice were euthanized 24h after the modeling, and cardiac samples were collected. Gene sequencing and western blot were utilized to identify potential hub genes and signaling pathways. Sevoflurane markedly reduced LPS-induced myocardial injury and cardiac dysfunction compared to the pentobarbital intervention. Transcriptome sequencing revealed that numerous genes exhibited differential expression following intervention with sevoflurane and pentobarbital, with predominant enrichment in the signaling pathways, such as the extracellular region and matrix, tumor necrosis factor (TNF), and p53 signaling. Sevoflurane significantly induced TATA-box binding protein-associated factor, RNA polymerase I subunit D (TAF1D) expression and attenuated cardiomyocyte death, oxidative stress, and the secretion of IL-6 and TNF-α compared to the pentobarbital group (p < 0.05). Furthermore, oe-TAF1D significantly exacerbated cardiomyocyte death, oxidative stress, and inflammatory responses, which were alleviated with si-TAF1D (p < 0.05). Sevoflurane mitigates sepsis-induced cell death, oxidative stress, and inflammatory responses by up-regulating TAF1D, consequently diminishing cardiac injury and preserving cardiac function.

Patients with pulmonary fibrosis are at a higher risk of developing pulmonary hypertension, a complication with poor prognosis. At present, the mechanism of this link is still poorly understood. A major obstacle to progress in this area is the lack of a reliable animal model to replicate PF-PH. This study aimed to establish a stable PF-PH rat model. Rats were fasted overnight prior to intervention. Under sodium pentobarbital anesthesia (45 mg/kg), the trachea was intubated with a PE50 tube inserted to a depth of 3 cm (the distance from the glottis to the tube). Bleomycin (BLM) was administered intratracheally as a single dose (5 mg/kg, dissolved in 0.2 mL of 0.9% NaCl). Following the injection, the rats were immediately rotated to ensure even distribution of the BLM. At 35 days after the BLM injection, the rats exhibited progressive impairment of lung function and increased right ventricular systolic pressure and right ventricular hypertrophy, revealing the pathological characteristics of pulmonary hypertension.We provide a general and reliable method to establish a rat model of PF-PH.

One-third of individuals without underlying health conditions and 60% of individuals with elevated blood pressure (BP) are salt-sensitive. A shift from low to high Na + diet is linked to higher BP. Inverse salt sensitivity is an increase in BP when Na+ intake is reduced. This affects about 10-15% of the population but the mechanisms underlying this alteration in BP are not understood. The renal dopamine D2 receptor (D2R) plays a critical role in maintaining normal BP and preventing inflammation and tissue injury. The DRD2 gene is highly polymorphic and single nucleotide polymorphisms of this gene have been linked to allelic variations that impair receptor synthesis and stability. In particular, the rs6277 SNP in exon 7 of DRD2 is associated with decreased D2R expression and found in some humans with elevated blood pressure or hypertension. We have also reported that human renal proximal tubular cells with this SNP have decreased mRNA and protein D2R expressions and increased expression of Na+ pump/transporters. To study the effects of this SNP on Na + balance and BP we generated, using CRISP-Cas9, mice expressing either the human D2R wild-type ( DRD2 WT) or the mutant expressing the rs6277 ( DRD2 Mut) in mice lacking their own Drd2. Female mice were placed for one week on three distinct salt diets: normal salt (NS; 0.4% NaCl) diet, high salt (HS; 4% NaCl), and low salt (LS; less than 0.08% NaCl) diets. On NS diet, BPs (measured by tail-cuff under pentobarbital anesthesia) were similar in DRD2 WT and DRD2 Mut mice (79±3 vs 81±5 mm Hg; n=4/group). On HS diet, BPs were also similar in both groups (85±3 vs 86±5 mm Hg; n=4/group). However, on LS diet DRD2 Mut mice had significantly higher BPs than DRD2 WT (89±5 vs 71±1 mm Hg, p&lt;0.05; n=4/group) mice. In DRD2 WT mice, BP increased on HS diet and decreased on LS, while in DRD2 Mut mice, BP increased on LS but their BPs were not different between NS and HS diet. On LS diet, UNaV was lower in DRD2 Mut than DRD2 WT mice (0.003±0.001 vs 0.008±0.001 mEq/day; p&lt;0.05; n=4/group) but on HS diet, UnaV was higher in DRD2 Mut than DRD2 WT (0.91±0.3 vs 0.44±0.07; p&lt;0.05; n=3/group) mice. Preliminary data in male mice show the same alterations. These findings suggest that alterations in DRD2 expression/function may be the underlying cause of inverse salt sensitivity because the presence of DRD2 rs6277 is associated with inverse salt sensitivity in humans. NIH-NIDDK R01Actf DK134574Projectf 01 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

The mesopontine tegmental anesthesia area (MPTA) is a focal brainstem locus which, when exposed to GABAergic agents, induces brain-state transitioning from wakefulness to unconsciousness. Correspondingly, MPTA lesions render animals relatively insensitive to GABAergic anesthetics delivered systemically. Using chemogenetics, we recently identified a neuronal subpopulation within the MPTA whose excitation induces this same pro-anesthetic effect. However, very few of these "effector-neurons" express synaptic γ2-containing GABAA receptor isoforms and none express extrasynaptic δ-subunit containing receptors, suggesting that they are not the direct cellular target of GABAergic agents. Here we used pharmacological tools in rats to define the molecular target(s) of GABAergics in the MPTA. GABA microinjected into the MPTA at nanomolar concentrations, selective for GABAAδ-Rs, proved to be pro-anesthetic as was blocking GABA reuptake. Likewise, low-concentration gaboxadol/THIP, also selective for GABAAδ-Rs, was effective, whereas benzodiazepines and zolpidem, which selectively target GABAAγ2-Rs, were not. The GABAergic anesthetics pentobarbital and propofol proved pro-anesthetic when applied to the MPTA at the low concentrations present in the brain after systemic dosing. Glycinergic agonists which are inhibitory, but infective on GABAAδ-Rs, and other non-GABAergic agonists tested, were at most only marginally effective. We conclude that GABAAδ-Rs are the primary molecular target of GABAergic anesthetics in the MPTA. Immunolabeling revealed that this GABAA-R isoform is expressed exclusively by a distinct subpopulation of MPTA "δ-cells" that reside in close apposition to effector neurons. This suggests that during wakefulness, δ-cells serve as inhibitory interneurons which, when silenced by GABAergic agents, disinhibit (excite) the effector-neurons, triggering transition to unconsciousness.

This study investigates the effect of agmatine on reducing mortality, neurobehavioral alterations, infarct size, and expression of pro-inflammatory cytokines in mice subjected to bilateral carotid thrombosis. Under pentobarbital anesthesia, the left common carotid artery was exposed to 6% FeCl3. Thirty-two days later, the same procedure was performed on the right common carotid artery. Subsequently, Agmatine (100 mg/kg) was administered 15 min after the second procedure, and in another experimental group, the dose of Agmatine was repeated at 72 h. Administration of agmatine extended survival in ischemic animals up to 72 h for the single-dose group and up to 96 h for the repeated-dose group, without significant increases in neurological deficits or infarct area size. This neurobehavioral effect was also observed in sham animals treated with agmatine. In ischemic animals, agmatine administration improved digging behavior and reduced recovery times, consistently shorter in those animals treated with repeated doses. RT-PCR analyses revealed a positive regulation of the cytokine IL-1β in agmatine-treated animals, which has been associated with recovery stages. The results suggest that the observed effect may be attributed to the multiple interactions of agmatine with ischemic cascade events, highlighting its anti-inflammatory role.

Compared with the use of ultrasound for noninvasive monitoring of the anesthetic sodium pentobarbital versus tribromoethanol in an animal model of renal ischemia-reperfusion injury in rats. Adult rats were randomly assigned to a renal ischemia-reperfusion injury model, and preoperative anesthetics were administered as either sodium pentobarbital or tribromoethanol. Color Doppler ultrasound and spectral Doppler ultrasound were used to detect changes in respiratory rate and heart rate during and after the surgery, as well as measure renal hemodynamic parameters including peak systolic velocity, end-diastolic velocity, and resistance index. The frequency of changes in respiration and heart rate was significantly higher in the sodium pentobarbital anesthesia group compared to the tribromoethanol anesthesia group. The peak systolic velocity and end-diastolic velocity values in the sodium pentobarbital anesthesia group were significantly lower than those in the tribromoethanol group. However, the resistance index in the sodium pentobarbital group was higher than that in the tribromoethanol group. Ultrasound can be used to dynamically monitor the effects of anesthesia during the experiment, including changes in respiratory rate and heart rate, as well as semi-quantitatively monitor hemodynamic changes in the kidneys, which indirectly reflects whole-body hemodynamic changes in rats.

Mitigation of cisplatin-induced cardiotoxicity by Isorhamnetin: Mechanistic insights into oxidative stress, inflammation, and apoptosis modulation

Introduction: Breast cancer (BC), the predominant non-melanoma cancer among women, is projected to escalate to more than 3 million new cases and ~1 million fatalities globally by 2040. Chronic and fluctuating low oxygen (O2) conditions within tumors favor malignant growth, decreased responsiveness to therapeutic interventions, and reduced patient survivability. Treatment strategies to combat tumor hypoxia are desperately needed. Dietary nitrate supplementation via beetroot juice (BRJ), which increases nitric oxide (NO) production through the nitrate-nitrite-NO pathway, has been demonstrated to increase skeletal muscle blood flow, improve mitochondrial effciency, and reduce metabolic demands. Specifically, BRJ improves interstitial oxygen pressures (PO2 is) in acidic, low oxygen environments such as that found in the tumor microenvironment. Therefore, we hypothesized that BRJ supplementation would increase PO2 is in BC tumors. Methods: Female Fischer 344 retired breeder rats (6-8 months old) were used in this investigation. Adenocarcinoma cells (MAT B III at 6 x 103) were injected into the mammary duct and tumor growth was monitored over 2 weeks. Once tumors reached ~5 mm in diameter, rats were randomly assigned to consume BRJ (1 mmol/kg/day; BRJ, n=3) or water (CON; n=3) for 5 days. Under pentobarbital anesthesia, tumor PO2 is measurements were obtained using phosphorescence quenching. Results: Tumor growth rate was decreased in BRJ compared to CON rats (0.5 ± 0.1 vs. 1.0 ± 0.1 mm/day; p&lt;0.05). Heart rate and mean arterial pressure were not different between groups (P&gt;0.05). Blood lactate was significantly decreased in BRJ compared to CON rats (0.5 ± 0.1 vs. 1.2 ± 0.1 mmol/L, p&lt;0.05). There was an increase in mean tumor PO2 is in BRJ vs. control rats (6.9 ± 1.3 vs. 3.7 ± 0.47; p&lt;0.05). Conclusions: This study offers promising preliminary insights into the potential of dietary nitrate supplementation as an adjunctive approach to BC treatment to increase tumor PO2 is and reduce tumor growth rate. Future and ongoing studies will increase the sample size, use fluorescent microspheres to measure tumor blood flow, and explore the potential for BRJ and other NO agonists to combat tumor hypoxia and the skeletal muscle dysfunction associated with cancer progression. This research was funded by the following sources: the Johnson Cancer Research Center Innovative Research Award and Sustained Momentum for Investigators with Laboratories Established (SMILE) Grants at Kansas State University, the National Institute on Aging (Grant 1R15AG078060), and Ruth L. Kirschstein National Research Service Awards from the National Heart, Lung, and Blood Institute (Grants 1F31HL167618-01 and 1F31HL170643-01). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Introduction: Acute hemorrhage decreases blood pressure (BP) and sometimes causes hypovolemic shock. At this time, peripheral arteries are supposed to contract and increase peripheral vascular resistance to raise BP. However, there has not been an adequate index of a degree of arterial stiffness. We assessed changes in arterial stiffness during rapid bleeding using new BP-independent vascular indices, aBeta and ifBeta, determined by applying the cardio-ankle vascular index theory to the elastic (aorta) and muscular (common iliac-femoral) arteries, respectively, in rabbits. Methods: Eleven Japanese white male rabbits were fixed at the supine position under pentobarbital anesthesia. Fifteen percent of the total blood volume was depleted at a rate of 2 mL/kg/min for 6 min; 15 min later, the withdrawn blood was re-transfused at the same rate. Pressure waves at the origin of the aorta (oA), distal end of the abdominal aorta (dA), distal end of the left common iliac artery (fA), and flow waves at oA were measured simultaneously. Beta was calculated using the following formula: beta = 2ρ/PP × ln(SBP/DBP) × PWV2, where ρ, SBP, DBP, and PP are blood density, systolic, diastolic, and pulse pressures, respectively. aBeta, ifBeta, and aortic-iliac-femoral beta (aifBeta) were calculated using aPWV, ifPWV, and aifPWV, respectively. Results: BP declined significantly at oA, dA, and fA during the acute bleeding. aBeta and aifBeta increased significantly from 3.7 and 5.0 before the bleeding (control) to 5.0 (about 34%) and 6.3 (about 26%) on average, while ifBeta decreased significantly from 20.5 before the bleeding to 17.1 (about 17%) after the completion of the bleeding. Reverse reactions of those indices were observed by transfusing the removed blood. Conclusion: Total arterial stiffness (aifBeta) increased; however, the elastic and muscular arteries stiffened and softened during the bleeding, respectively. These results would give useful diagnostic information during fall in BP.

Background: The progression from acute kidney injury to chronic kidney disease poses a significant health challenge. Nonetheless, a constraint in existing animal models of renal ischemia/reperfusion (I/R) injury is the necessity for a severe injury, almost reaching a life-threatening level, to trigger the subsequent onset of renal fibrosis. Hence, we explored an adapted gradient approach to induce I/R injury, aiming to promote the progression of renal fibrosis while preserving the overall normal functioning of the kidney. Methods: In each group, 6-8 male C57BL/6 mice were used for model construction, with all undergoing sodium pentobarbital anesthesia and left kidney removal. Subsequently, a silk thread was passed beneath the lower renal branch, elevating the right kidney under a 20-g weight's tension via a pulley system for durations of 30, 40, or 60min. Afterwards, we lowered the kidney, sutured the wound, and administered intraperitoneal saline. Mice in different groups were euthanized following reperfusion for 1, 3, 7, or 28days. Results: We observed a complete cessation of blood flow in the lower pole, while an incomplete cessation in the upper pole in the elevated kidney. Significant renal impairment was evident on day 1 with a 60min ischemic period (187.0 ± 65.3 vs 17.9 ± 4.8μmol/L serum creatinine in normal; p < .001), but not with 30 or 40min. On day 1, tubular necrosis and hyaline cast formation was evident in both lower and upper poles. On day 3, renal function returned to normal and remained normal through day 28. Histologic damage resolved in the upper pole over days 3 to 7, resulting in normal histology on day 28. By contrast, there was sustained tubular damage tubular in the lower pole on days 3 and 7, which failed to resolve and led to significant renal fibrosis by day 28. Conclusion: We created a model demonstrating clinically "silent" renal fibrosis.

BackgroundToll-like receptor 8 (TLR8) can recognize specific pathogen-associated molecular patterns and exert multiple immunological functions through activation of signaling cascades. However, the precise distribution and age-related alterations of TLR8 in the spleens of Bactrian camels have not yet been investigated. This study aimed to prepare a rabbit anti-Bactrian camel TLR8 polyclonal antibody and elucidate the distribution of TLR8 in the spleens of Bactrian camels at different age groups. The methodology involved the construction of the pET-28a-TLR8 recombinant plasmid, followed by the expression of TLR8 recombinant protein via prokaryotic expression. Subsequently, rabbits were immunized with the purified protein to prepare the TLR8 polyclonal antibody. Finally, twelve Alashan Bactrian camels were categorized into four groups: young (1–2 years), pubertal (3–5 years), middle-aged (6–16 years) and old (17–20 years). These camels received intravenous sodium pentobarbital (20 mg/kg) anesthesia and were exsanguinated to collect spleen samples. Immunohistochemical techniques were employed to observe and analyze the distribution patterns and age-related changes of TLR8 in the spleen.ResultsThe results showed that the TLR8 recombinant protein was expressed in the form of inclusion body with a molecular weight of 52 kDa, and the optimal induction condition involved 0.3 mmol/L IPTG induction for 8 h. The prepared antibody yielded a titer of 1:32 000, and the antibody demonstrated specific binding to TLR8 recombinant protein. TLR8 positive cells exhibited a consistent distribution pattern in the spleen across different age groups of Bactrian camels, primarily scattered within the periarterial lymphatic sheath of the white pulp, marginal zone, and red pulp. The predominant cell type expressing TLR8 was macrophages, with expression also observed in neutrophils and dendritic cells. Statistical analysis revealed that there were significant differences in the distribution density of TLR8 positive cells among different spleen regions at the same age, with the red pulp, marginal zone, and white pulp showing a descending order (P<0.05). Age-related changes indicated that the distribution density in the marginal zone and red pulp exhibited a similar trend of initially increasing and subsequently decreasing from young to old camels. As camels age, there was a significant decrease in the distribution density across all spleen regions (P<0.05).ConclusionsThe results confirmed that this study successfully prepared a rabbit anti-Bactrian camel TLR8 polyclonal antibody with good specificity. TLR8 positive cells were predominantly located in the red pulp and marginal zone of the spleen, signifying their pivotal role in the innate immune response of the spleen. Aging was found to significantly reduce the density of TLR8 positive cells, while leaving their scattered distribution characteristics unaffected. These findings provide valuable support for further investigations into the immunomorphology and immunosenescence of the spleen in Bactrian camels.

Pentobarbital and isoflurane are commonly used veterinary anesthetics. Due to the dangers of overdose by repeat-bolus regimen of pentobarbital, isoflurane has been recommended. However, literature suggests isoflurane-induced inhibition of cytokine and adhesion molecule release, impacting leukocyte adhesion. This study aims to characterize the impacts of pentobarbital versus isoflurane on leukocyte interactions within the intestinal microcirculation with and without endotoxin challenge. Female BALB/c mice were subjected to pentobarbital or isoflurane (N = 20) and challenged with endotoxin or saline by intraperitoneal injection. The mice were kept under anesthesia for 2 hours. Fluorochromes, rhodamine-6 G and fluorescein isothiocyanate, were injected intravenously. To visualize leukocyte adhesion within the intestinal microcirculation, laparotomy and intravital microscopy was performed. Leukocyte rolling and adhesion was quantified offline in a blinded fashion. Within collecting venules, leukocyte rolling and adhesion showed no significant differences between pentobarbital and isoflurane anesthesia under basal conditions. Endotoxin challenge caused a similar response in both anesthetic groups. Within postcapillary venules, no statistical differences between the two anesthetics were found for adhering leukocytes under basal conditions or following endotoxin challenge either. However, leukocyte rolling after LPS-challenge was significantly decreased in postcapillary venules during isoflurane anesthesia compared to pentobarbital anesthesia. Isoflurane anesthesia showed only minor differences in the immune response to endotoxin within the intestinal microcirculation compared to pentobarbital anesthesia. Due to the superior safety profile of volatile anesthetics, immunological studies may choose isoflurane over pentobarbital as the veterinary anesthetic of choice.

Dopamine receptor D2 (Drd2) plays an important role in maintaining normal blood pressure (BP) by regulating renal Na + transport. Knockdown of Drd2 in renal proximal tubule cells (RPTCs) may affect BP and Na + transport differently between male and female mice. We studied the effects of Drd2 in RPTCs of the mouse kidney by generating Drd2 fl/fl , P SGLT2 ::Cre + mice (D2R PT-/- ) that lack D2R only in RPTC and Drd2 fl/fl , P SGLT2 ::Cre - (D2R PT+/+ ) mice that do not have the deletion. The study was performed in male and female mice on normal (0.8% NaCl, NS) and low (0.025-0.05% NaCl; LS) salt diets. On NS diet mean arterial pressures (MAPs, mm Hg), measured under pentobarbital anesthesia, were similar in male D2R PT+/+ (86.38±2.20, n=13) and D2R PT-/- (91.58±1.63, n=19) and female D2R PT+/+ (82.57±2.33, n=14) and D2R PT-/- (85.17±6.09, n=12) mice . By contrast, in D2R PT-/- mice, LS diet similarly increased MAP in male (108.11±7.04 (n=10) and female (103.00±9.98 (n=5) mice. The renal NHE3 protein expression (%) was higher in male than female mice (D2R PT+/+ : 100±4 (male) vs 30±15 (female); n=8/group; P&lt;0.0001; D2R PT-/- 117±10 (male) vs 44±16 (female); n=8/group; P&lt;0.02 ). However, NKCC expression (%) was higher in female than male D2R PT+/+ (788±10 (female) vs 100±4 (male), n=8/group; P&lt;0.01); there was no difference between D2R PT-/- male and female mice. The expressions of Na + -K + /ATPase, NCC, SGLT2, and ENaC were similar in males and females of the two genotypes. These findings suggest that on LS diet D2R knockdown in the RPTC increases BP in both male and female mice but the changes in NHE3 and NKCC expressions are different between male and female mice. These results suggests that the MAP response to salt intake is not affected by sex but the renal mechanisms involved are sex-related.

Background: Cucumis sativus (cucumber) is regarded as a healthy fruit because of the beneficial effects of its phytochemical constituents. However, there is a deficit of information about its effect on male reproductive physiology. Objective: This study was conducted to investigate the effect of aqueous extract of C. sativus (AECS) on male reproductive hormones, oxidative stress biomarkers, and lipid profile. Materials and Methods: Ten male rats were randomly assigned into two (control and treated) groups (n = 5). In the treated group, a single dose of AECS (500 mg/kg) was administered daily for 6 weeks and thereafter sacrificed under sodium pentobarbital anesthesia. Blood was collected and analyzed for sex hormones, antioxidants, and lipid profile markers. The testicular homogenate was also analyzed for antioxidants. Results: The AECS increased (P &lt; 0.05) serum testosterone and luteinizing hormone levels (4.43 ± 0.34 and 7.50 ± 1.31, respectively) when compared with the control. Also, testicular catalase and serum level of high-density lipoprotein were increased (27.45 ± 0.19 and 30.08 ± 5.22, respectively) (P &lt; 0.05), whereas serum low-density lipoprotein decreased (72.79 ± 9.56) (P &lt; 0.05) in the extract treated rats. However, serum antioxidant levels were not affected. Conclusions: AECS is beneficial to male reproductive physiology evidenced by improved lipid profile and hormonal indices. Also, the integrity of the testicular redox profile was well maintained.

Aim: Central systolic blood pressure (cSBP) was closely related to hypertension-related organ damage rather than peripheral systolic blood pressure (pSBP). We aimed to estimate cSBP from pSBP without generalized transfer function in normal and Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits aged 12 months.Methods: Two catheter-tip transducers were advanced into the ascending aorta (AA) and distal end of the right brachial artery (Br) through the right common carotid and right radial arteries, respectively, under pentobarbital anesthesia. Pressure waves in response to the intravenous administration of angiotensin II and sodium nitroprusside were simultaneously recorded in AA and Br under regular cardiac pacing.Results: The first (pSBP) and second peaks (pSBP2) of the brachial blood pressure and their average (pSBPm) were significantly correlated with cSBP, despite Murgo’s wave pattern of central pressure waves in both rabbit groups. In Bland–Altman plot and its modification as a function of the peripheral augmentation index (pAI) analyses, the differences between pSBP and cSBP decreased, and those between pSBP2 and cSBP increased significantly in their average- or pAI-dependent manner, with undeniable mean biases in both rabbit groups. When the same analyses for SBPm were performed instead, the mean bias was around zero, with reduced variance in the two rabbit groups. The observed pressure or pAI-dependent systematic biases for pSBP and pSBP2 disappeared, representing the precise feature of pSBPm as a cSBP estimate.Conclusions: We conclude that pSBPm could be more precise than pSBP2 as a cSBP estimate, irrespective of blood pressure levels, pAI, or the presence of atherosclerosis.

This study evaluated nickel and aluminium-induced neurotoxicity, as a binary metal mixture. Twenty-eight male Sprague Dawley albino rats were weight-matched and divided into four groups. Group 1 (control) received deionized water. Group 2 and 3 received Aluminium (1 mg/kg) and Nickel (0.2 mg/kg) respectively, while Group 4 received Ni and Al mixture HMM three times a week orally for 90 days. Barnes maze tests was performed. Rats were sacrificed under pentobarbital anaesthesia, cerebral cortex and hippocampus were separated, and metal levels were measured using Atomic Absorption Spectroscopy (AAS). Malondialdehyde (MDA), catalase (CAT), glutathione content (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), Brain Derived Neurotrophic Factor (BDNF), Nerve growth factor NGF, cyclo-oxygenase COX-2 and Acetylcholinesterase (AChE) were assayed using ELISA kits. Ni/Al binary mixture exposed rats showed a shorter latency period (though not significant) of 3.21 ± 1.40 s in comparison to 3.77 ± 1.11 (Ni only) and 3.99 ± 1.16(Al only). Ni/Al mixture gp had the lowest levels of Mg in both the hippocampus and frontal cortex when compared with the individual metals. In the hippocampus Al only exposed rats significantly showed p < 0.05 higher iron and Ca levels in comparison to Ni/Al mixture. Al alone significantly showed p < 0.05 lower levels of Fe but higher Ca than the Ni/Al mixture group. Exposure to Al only showed lower levels of BDNF in comparison to Ni/Al combination, whereas Ni/Al mixture gp had lower levels of NGF in comparison to the individual metals in the hippocampus. In the frontal cortex Ni only, group showed significantly lower BDNF in comparison to Ni/Al mixture whereas the mixture showed significantly lower NGF when compared with Al only group. There were higher levels of COX-2 in the Ni/Al mixture than individual metal treated rats in both hippocampus and frontal cortex. AChE levels in the Ni/Al mixture group was higher than Ni or Al only gps in the hippocampus whereas in the frontal cortex, Ni/Al exposed rats showed significantly lower AChE levels in comparison to Al only group. Ni, Al and Ni/Al mixture exhibited memory impairment by activation of oxidative stress, COX-2, and diminution of AChE, BDNF and NGF levels in cerebral cortex and hippocampus. The BDNF-COX-2 AChE signalling pathway may be involved in the neurotoxicity of Ni and Al.

Banana peel ameliorated hepato-renal damage and exerted anti-inflammatory and anti-apoptotic effects in metal mixture mediated hepatic nephropathy by activation of Nrf2/ Hmox-1 and inhibition of Nfkb pathway.

Purpose: The aim of this study was to investigate the effects of different anesthetic agents on electroretinograms (ERGs) in Spontaneously Diabetic Torii fatty rats (SDT fatty rats). Methods: The ERG recordings were measured under general anesthesia using pentobarbital or a combination of medetomidine hydrochloride, midazolam, and butorphanol (MMB) tartrate anesthesia in 12 9-week-old normal Sprague-Dawley rats (Jcl:SD rats) and 16 SDT fatty rats. Each animal model was divided into 2 groups, the pentobarbital group and MMB group. The amplitudes and peak times of the a- and b-waves and oscillatory potentials (OPs) were measured from 0.0001 candela per square meter (cd.s/m²) to 10.0 cd.s/m². Results: The amplitude of the a-wave was significantly higher in the MMB group of Jcl:SD rats, but there was no significant difference in amplitude between the two groups of SDT fatty rats. There was no significant difference in the OP1 amplitude between both groups of Jcl:SD rats, but the OP1 amplitude was significantly higher in the MMB group of SDT fatty rats. The OP2 amplitude was significantly higher in the pentobarbital group in both the Jcl:SD rats and SDT fatty rats. There was no significant difference in the OP3 amplitude between the Jcl:SD and SDT fatty rat groups. The amplitude of the OP4 waves was significantly higher in the MMB group for both Jcl:SD and SDT fatty rats. There was no significant difference in the sums of the OP1 to OP4 (ΣOPs) amplitudes between the Jcl:SD and SDT fatty rat groups. There was no significant difference in the b-wave amplitude between the Jcl:SD rat groups, but the b-wave amplitude was significantly higher in the SDT fatty rats that received pentobarbital. The peak times for a-wave, OP1, OP2, OP3, OP4, and ΣOPs were significantly longer in the pentobarbital group of SD rats. The peak time of the b-wave was significantly longer in the MMB group of Jcl:SD rats, but the same result was obtained in the SDT fatty rats except that there was no significant difference in the a-wave. Conclusion: The overall ERG results vary depending on the anesthetic agent used. The OPs can be observed in detail when using MMB. Since the SDT fatty rat is a diabetic model animal, we recommend MMB as the anesthesia of choice when studying the OP waves in detail.