Protective Effects of Curcumin and Nanomicelle Curcumin on Chlorpyrifos-induced Oxidative Damage and Inflammation in the Uterus, Ovary and Brain of Rats.

BACKGROUND AND AIMS: Chlorpyrifos (CPF), which is classified as an Organophosphorus Pesticide (OP), has been identified as a toxic agent for the reproductive system due to its capacity to induce oxidative stress and inflammation. Curcumin (CUR) has been reported as a natural antioxidant and anti-inflammatory agent that could combat toxicity in various tissues. This study aims to examine the protective effects of CUR and its nanoformulation against reproductive impairment induced by CPF. METHOD: Forty-eight female Wistar albino rats were randomly allocated to six groups (n=8): control (0.5 mL of corn oil, the solvent for CPF), CPF (10 mg/kg), CPF + CUR 100 mg/kg/day, CPF + CUR 300 mg/kg/day, CPF + nano-micelle curcumin (NMC) 2.5 mg/kg/day, and CPF + NMC 5 mg/kg/day. The experimental treatment was performed for 30 days. Then, brain, ovary and uterus tissues were collected for measuring oxidative stress and inflammatory indices. RESULT: MDA, NO, IL-6, and TNF-α concentrations significantly increased in the brain, ovary and uterus of the CPF group versus the control group (p < 0.001). The levels of GSH and SOD in the uterus, ovaries, and brain exhibited a significant decrease in the CPF group compared to the control group (p < 0.05). However, CUR (300 mg/kg) and NMC (5 mg/kg) significantly decreased MDA, NO, TNF-α, and Il-6 and increased SOD and GSH levels in the uterus, ovaries and brain of the CPF-exposed animals versus the CPF-exposed non-treated animals (p < 0.001). CONCLUSION: Our findings indicated that CUR and NMC could be effective in alleviating CPFinduced reproductive toxicity.

Relationships between trace elements and cognitive and depressive behaviors in sprague dawley and wistar albino rats.

Introduction: This study investigates the effects of social isolation on mental health and cognitive functions in Sprague Dawley (SD) and Wistar Albino (WIS) rat strains, prompted by the heightened awareness of such impacts amid the COVID-19 pandemic. This study aims to explore the impact of social isolation on memory, learning, and behavioral changes in middle-aged SD and WIS rat strains and to investigate cortical trace element levels, seeking potential correlations between these levels and the observed behavioral responses to social isolation. Methods: Four groups of 14-month-old male rats were established: control and isolated SDs and WIS rats (CONT-SD, ISO-SD, CONT-WIS, ISO-WIS). Morris Water Maze and Porsolt Forced Swimming tests were conducted for behavioral assessment. Following behavioral tests, rats were sacrificed under general anesthesia, and cortices were isolated for analysis of macro and trace element levels (ICP/MS). Results: In behavioral tests, CONT-SD rats exhibited superior performance in the Morris Water Maze test compared to CONT-WIS rats, but displayed increased depressive behaviors following social isolation, as evident in the Porsolt Forced Swimming test (p < 0.05). ISO-SD rats showed elevated levels of Co and Cu, along with reduced levels of Cs and As, compared to ISO-WIS rats. Moreover, isolation resulted in decreased Cu and Mo levels but increased Rb levels in WIS rats. Comparison of trace element levels in naïve groups from different strains revealed lower Zn levels in the WIS group compared to SD rats. Discussion: The findings suggest that the SD strain learns faster, but is more susceptible to depression after isolation compared to the WIS strain. Increased Co and Cu levels in ISO-SD align with previous findings, indicating potential trace element involvement in stress responses. Understanding these mechanisms could pave the way for preventive treatment strategies or therapeutic targets against the consequences of stressors, contributing to research and measures promoting a balanced diet to mitigate neurobehavioral abnormalities associated with social isolation in the future.

Stress hyper-reactivity increases vulnerability to developing binge-type eating and associated anxiety-like behavior; comparison between Wistar-Kyoto and Sprague-Dawley rats.

Introduction: Binge eating disorder (BED) is a widespread eating disorder that primarily affects women worldwide, and it is characterized by the presence of binge eating episodes and the absence of any compensatory behavior to prevent weight gain. BED presents elevated comorbidity with other psychiatric disorders, such as anxiety, and it has been suggested that stress sensibility could be a vulnerability factor for the development of BED and the associated anxiety comorbidity. In this study, we aim to investigate whether the Wistar-Kyoto rat strain (WKY), which has a stress hyper-reactive phenotype, could develop both binge-type eating and anxiety-like behaviors simultaneously. We also aim to compare its vulnerability to developing both behaviors with the Sprague Dawley rat strain (SD), a rat strain commonly used in binge-eating models. Methods: WKY and SD rats were subjected to the model of intermittent access to palatable food (sucrose solution 30% or shortening) without calorie restriction or stress exposure. We evaluated and compared the development of binge-type eating behavior, anxiety-like behavior, and serum corticosterone variation as an index of the stress response in both rat strains. Results: WKY rats presented a higher percentage of binge-type eaters and required less time to develop binge-type eating behavior than SD rats. The WKY eating pattern emulated a binge-eating episode regardless of the palatable food. Although the development of sucrose binge-type eating was similar between strains, WKY developed more easily the shortening binge-type eating than SD and was more susceptible to developing anxiety-like behavior. Additionally, sucrose binge eating seems to differentially affect both strains' hypothalamic-pituitary-adrenal (HPA) axis response to stress since it facilitated its response in SD and blunted it in WKY. Discussion: Our results show that high-stress sensitive phenotype is a common vulnerability factor for the development of binge-type eating and anxiety-like behavior. Regardless of the macronutrient composition of the palatable food, WKY is susceptible to developing a binge-type eating behavior and is more susceptible than SD to developing anxiety-like behavior simultaneously. In conclusion, results showed that a hyper-reactive stress phenotype predisposes the development of binge-type eating behavior and anxiety-like behavior in the absence of calorie restriction and stress exposure.

Unmoving and uninflamed: Characterizing neuroinflammatory dysfunction in the Wistar-Kyoto rat model of depression.

Reductionistic research on depressive disorders has been hampered by the limitations of animal models. Recently, it has been hypothesized that neuroinflammation is a key player in depressive disorders. The Wistar-Kyoto (WKY) rat is an often-used animal model of depression, but no information so far exists on its neuroinflammatory profile. As such, we compared male young adult WKY rats to Wistar (WS) controls, with regard to both behavioral performance and brain levels of key neuroinflammatory markers. We first assessed anxiety- and depression-like behaviors in a battery consisting of the Elevated Plus Maze (EPM), the Novelty Suppressed Feeding (NSFT), Open Field (OFT), Social Interaction (SIT), Forced Swim (FST), Sucrose Preference (SPT), and Splash tests (ST). We found that WKY rats displayed increased NSFT feeding latency, decreased OFT center zone permanence, decreased EPM open arm permanence, decreased SIT interaction time, and increased immobility in the FST. However, WKY rats also evidenced marked hypolocomotion, which is likely to confound performance in such tests. Interestingly, WKY rats performed similarly, or even above, to WS levels in the SPT and ST, in which altered locomotion is not a significant confound. In a separate cohort, we assessed prefrontal cortex (PFC), hippocampus and amygdala levels of markers of astrocytic (GFAP, S100A10) and microglial (Iba1, CD86, Ym1) activation status, as well as of three key proinflammatory cytokines (IL-1ß, IL-6, TNF-α). There were no significant differences between strains in any of these markers, in any of the regions assessed. Overall, results highlight that behavioral data obtained with WKY rats as a model of depression must be carefully interpreted, considering the marked locomotor activity deficits displayed. Furthermore, our data suggest that, despite WKY rats replicating many depression-associated neurobiological alterations, as shown by others, this is not the case for neuroinflammation-related alterations, thus representing a novel limitation of this model.

Effects of fecal microbiota transplantation on metabolic health of DBA mice.

Introduction: Numerous studies have demonstrated that C57BL/6 mice exhibit superior growth rates and overall growth performance compared to DBA mice. To investigate whether this discrepancy in growth performance is linked to the composition of gut microorganisms, we conducted fecal microbiome transplantation (FMT) experiments. Methods: Specifically, we transplanted fecal fluids from adult C57BL/6 mice, high-fat C57BL/6 mice, and Wistar rats into weaned DBA mice (0.2mL/d), and subsequently analyzed their gut contents and gene expression through 16S rRNA sequencing and transcriptome sequencing. During the test period, C57BL/6 mice and Wistar rats were provided with a normal diet, and high-fat C57BL/6 mice were provided with a high-fat diet. Results: The results of our study revealed that mice receiving FMT from all three donor groups exhibited significantly higher daily weight gain and serum triglyceride (TG) levels compared to mice of CK group. 16S rRNA sequensing unveiled substantial differences in the abundance and function of the gut microbiota between the FMT groups and the CK group. Transcriptome analysis revealed a total of 988 differential genes, consisting of 759 up-regulated genes and 187 down-regulated genes, between the three experimental groups and the CK group. Functional Gene Ontology (GO) annotation suggested that these genes were primarily linked to lipid metabolism, coagulation, and immunity. Pearson correlation analysis was performed on the differential genes and clusters, and it revealed significant correlations, mainly related to processes such as fatty acid metabolism, fat digestion and absorption, and cholesterol metabolism. Discussion: In summary, FMT from dominant strains improved the growth performance of DBA mice, including body weight gain, institutional growth, and immune performance. This change may be due to the increase of probiotic content in the intestinal tract by FMT and subsequent alteration of intestinal gene expression. However, the effects of cross-species fecal transplantation on the intestinal flora and gene expression of recipient mice were not significant.

Creating a Reproducible Model of Spinal Cord Injury in Rats: A Contusion Approach.

Spinal cord injury (SCI) is a devastating clinical condition that affects millions of people worldwide. SCI primarily affects males in younger age groups. It is characterized by a complex of neurological dysfunctions that can lead to permanent disability. We describe an adapted technique for SCI, i.e., a contusion model of SCI, in this chapter. This model is widely used to study the pathology of SCI and test potential therapies. The experimental contusion is performed by using a compression device, which allows the creation of a reproducible injury animal model through the definition of specific injury parameters. A detailed methodology has been developed and described here that utilizes a stereotactic frame and impactor to produce reproducible injuries.

Maltodextrin from Sweet Cassava: A Promising Endurance Enhancer.

The effects of maltodextrin and crude extract from sweet cassava on exercise endurance were examined in the male Wistar rat. The rats were randomly assigned to either an exercise training group or a non-exercise training group. Both groups were further divided into subgroups that received either a control, crude extract (250 or 500 mg/kg), or maltodextrin (250 or 500 mg/kg) orally once daily for 16 days. The time to the point of exhaustion after weight-loaded forced swimming was measured on day 16. Body weight gain, relative organ weight, biochemical parameters, and liver and gastrocnemius muscle glycogen content were also determined. Maltodextrin at a dose of 500 mg/kg significantly increased the time to the point of exhaustion compared to all other groups. Maltodextrin and crude extract with both doses significantly increased liver and gastrocnemius muscle glycogen content compared to the control group. There were no significant differences in glucose, BUN, triglyceride, or insulin levels between the groups. Crude extract at a dose of 250 mg/kg significantly increased AST and ALT levels, and LDH levels significantly increased in the exercise training group. Creatinine levels were significantly higher in the exercise training group compared to the non-exercise training group. Exercise boosted antioxidant enzymes, glycogen, and reduced damaging free radicals in the rats. Maltodextrin and crude extract further amplified this effect by activating AMPK and PGC-1α, suggesting that they combat fatigue through an antioxidant pathway linked to AMPK. These findings suggest that maltodextrin and crude extract from sweet cassava may have the potential to enhance exercise endurance. They may increase glycogen storage in the liver and gastrocnemius muscle, potentially through improved glycogen reserves and glycogen sparing effects. Further studies are needed to elucidate the mechanisms underlying these effects.

The Effects of High Fat Diet on the Incidence of Obesity and Monocyte Chemoattractant Protein-1 Levels on Histological Changes in Prostate Wistar Rats.

Introduction: Benign prostatic hyperplasia (BPH) is a histopathological diagnosis characterized by the increase in stromal cells and epithelial cells of the prostate gland in the transitional zone surrounding the urethra. Obesity is the risk factor of BPH. The most frequent cause of obesity is a high-fat diet (HFD). Obesity and HFD lead to pro-inflammatory conditions. One of the pathomechanisms for the occurrence of BPH is a low-degree inflammatory factor, one of which is the level of monocyte chemoattractant protein-1/MCP-1. This study aims to determine the influence of HFD on the incidence of obesity and inflammatory factors (monocyte chemoattractant protein-1/MCP-1 levels) on the histopathological picture of the prostate. Methods: Experimental research was performed on male Wistar rats with each of the 6 rats given normal fat (ND) and HFD intake and terminated at 8 weeks and 6 rats given each ND and HFD were terminated at 16 weeks. The determination of obesity was determined based on Lee's criteria which were categorized as obese if the Lee index >0.3 and non-obese if ≤0.3. Examination of circulating MCP-1 was carried out by the ELISA method and determination of prostatic hyperplasia was done by calculating the percentage of prostate glands that had a large per-field cystic dilatation on light microscopy examination. All data are analyzed statistically with the Fisher Exact Test and Spearman Correlation Test. Results: Of the 12 rats that were given ND, none of them became obese according to Lee's criteria, on the other hand, of the 12 rats that were given HFD 8 became obese (66.7%, p = 0.001). Serum MCP-1 levels and the percentage of prostate glands that had cystic dilatation were significantly higher in mice receiving HFD than ND; both at week-8 (MCP-1; 18.87 vs 15.66) and (prostate gland experiencing cystic dilatation; 63.46% vs 47.24%) and week-16 (MCP-1; 21.27 vs 21.27) and (prostate gland experiencing cystic dilatation; 67.79% vs 56.39%). Spearman correlation analysis showed that only circulating MCP-1 levels were significantly correlated (p < 0.05) to the percentage of the prostate gland that had cystic dilatation; especially in week 16 (r = 0.713 and p < 0.001). At 8 weeks, it was not statistically significant (r = 0.406 and p = 0.095). Conclusion: High fat intake has been shown to increase the risk of obesity, but obesity does not increase inflammatory status and the incidence of prostate glands with cystic dilatation. On the other hand, high-fat intake increases inflammatory status which in turn causes prostate glands to develop cystic dilatation.

Effects of Exercise Training and L-Arginine Loaded Chitosan Nanoparticles on Hippocampus Histopathology, ß-Secretase Enzyme Function, APP, Tau, Iba1and APOE-4 mRNA in Aging Rats.

The objective of this study was to evaluate the combined and independent effects of exercise training and L-Arginine loaded chitosan nanoparticles (LA CNPs) supplementation on hippocampal Tau, App, Iba1, and ApoE gene expression, oxidative stress, ß-secretase enzyme activity, and hippocampus histopathology in aging rats. Thirty-five male Wistar rats were randomly assigned to five groups (n = 7 in each): Young (8 weeks old), Old (20 months old), old + L-arginine supplementation (Old Sup), old + exercise (Old Exe) and old + L-arginine supplementation + exercise (Old Sup + Exe). LA CNPs were administered to the supplement groups through gavage at a dosage of 500 mg/kg/day for 6-weeks. Exercise groups were subjected to a swimming exercise program five days/week for the same duration. Upon the completion of their interventions, the animals underwent behavioral and open-field task tests and were subsequently sacrificed for hippocampus genetic and histopathological evaluation. For histopathological analysis of brain, Cresyl violet staining was used. Congo Red staining was employed to confirm amyloid plaques in the hippocampus. Expressions of Tau, App, Iba1, and ApoE genes were determined by real-time PCR. In contrast to the Old group, Old Exe and Old Sup + Exe groups spent more time in the central space in the open field task (p < 0.05) and have more live cells in the hippocampus. Old rats (Old, Old Sup and Old Exe groups) exhibited a significant Aß peptide accumulation and increases in APP, Tau, Iba1, APOE-4 mRNA and MDA, along with decreases in SOD compared to the young group (p < 0.05). However, LA CNPs supplementation, exercise, and their combination (Old Sup, Old Exe and Old Sup + Exe) significantly reduced MDA, Aß plaque as well as APP, Tau, Iba1, and APOE-4 mRNA compared to the Old group (p < 0.05). Consequently, the administration of LA CNPs supplements and exercise might regulate the risk factors of hippocampus cell and tissue.

Changes in cardiovascular autonomic control induced by chronic inhibition of acetylcholinesterase during pyridostigmine or donepezil treatment of spontaneously hypertensive rats.

Chronic treatment with acetylcholinesterase inhibitors may be a promising therapeutic strategy for treatment of cardiovascular diseases. The aim of our study was to analyze the changes in blood pressure (BP) and heart rate (HR) during 14 days of treatment with two different acetylcholinesterase inhibitors - pyridostigmine (PYR) having only peripheral effects or donepezil (DON) with both peripheral and central effects. In addition, we studied their effects on the cardiovascular response to restraint stress and on sympathovagal control of HR in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). SHR were characterized by elevated BP and increased low-frequency component of systolic BP variability (LF-SBPV), but their cardiac vagal tone and HR variability (HRV) were reduced compared with WKY. Chronic treatment with either acetylcholinesterase inhibitor decreased HR and increased HRV in both strains. PYR treatment slightly decreased BP and LF-SBPV in the dark phase of the day. Neither drug significantly altered BP response to stress, but PYR attenuated HR increase during restraint stress. Regarding sympathovagal balance, acute methylatropine administration caused a greater increase of HR in WKY than in SHR. Chronic PYR or DON treatment enhanced HRV and HR response to methylatropine (vagal tone) in WKY, whereas PYR but not DON treatment potentiated HRV and vagal tone in SHR. In conclusion, vagal tone was lower in SHR compared with WKY, but was enhanced by chronic PYR treatment in both strains. Thus, chronic peripheral, but not central, acetylcholinesterase inhibition has major effects on HR and its variability in both normotensive and hypertensive rats.

Insular and prelimbic cortices control behavioral accuracy and precision in a temporal decision-making task in rats.

The anterior insular cortex (AIC) comprises a region of sensory integration. It appears to detect salient events in order to guide goal-directed behavior, code tracking errors, and estimate the passage of time. Temporal processing in the AIC may be instantiated by the integration of representations of interoception. Projections between the AIC and the medial prefrontal cortex (mPFC) - found both in rats and humans - also suggest a possible role for these structures in the integration of autonomic responses during ongoing behavior. Few studies, however, have investigated the role of AIC and mPFC in decision-making and time estimation tasks. Moreover, their findings are not consistent, so the relationship between temporal decision-making and those areas remains unclear. The present study employed bilateral inactivations to explore the role of AIC and prelimbic cortex (PL) in rats during a temporal decision-making task. In this task, two levers are available simultaneously (but only one is active), one predicting reinforcement after a short, and the other after a long-fixed interval. Optimal performance requires a switch from the short to the long lever after the short-fixed interval elapsed and no reinforcement was delivered. Switch behavior from the short to the long lever was dependent on AIC and PL. During AIC inactivation, switch latencies became more variable, while during PL inactivation switch latencies became both more variable and less accurate. These findings point to a dissociation between AIC and PL in temporal decision-making, suggesting that the AIC is important for temporal precision, and PL is important for both temporal accuracy and precision.

Ultrasound-guided and 'blind' sciatic nerve injection techniques: Comparison in rat cadavers.

OBJECTIVE: To compare the success rate and extent of sciatic nerve staining with a bupivacaine-dye solution using two injection techniques: 'blind' or ultrasound-guided approach. STUDY DESIGN: Prospective, experimental, randomized, cadaveric study. ANIMALS: Adult female Wistar rat cadavers [n = 24, mass 352 g (323-374)]. METHODS: Each sciatic nerve was randomly allocated to one of two groups: 'blind' (group B) or ultrasound-guided approach (group US) to injection. Following injection of bupivacaine-dye solution (0.1 mL), gross anatomical dissection was performed to visualize nerve staining, categorizing it as either positive or negative. The length of nerve staining was then measured and visual inspection conducted to identify potential nerve damage. Fisher's exact test was used to compare positive or negative nerve staining, and the Wilcoxon signed rank test used to compare the length of nerve staining between groups. RESULTS: In group B, the bupivacaine-dye solution stained 16/24 sciatic nerves (67% success). In group US, staining was successfully observed in all 24 nerves (100% success, p < 0.004). The length of nerve staining [median (interquartile range)] was 2 (2-3) mm in group B and 5 (4-6) mm in group US (p < 0.001). One sciatic nerve in group B had injectate distributed over 16 mm, suggestive of an intraneural injection. No signs of laceration or nerve damage were visible under 6× magnification in either group. CONCLUSIONS AND CLINICAL RELEVANCE: The ultrasound-guided approach for sciatic nerve injection demonstrated a higher success rate with superior injectate distribution when compared with the 'blind' approach. Ultrasound guidance is recommended over a 'blind' approach for sciatic nerve block in rats when possible.

Sex-dependent vulnerability for Wistar rats model following intranasal instillation with Klebsiella pneumoniae ATCC 43816 causing lobar pneumonia.

BACKGROUND: Klebsiella pneumoniae has become one of the major threats to public health as it causes nosocomial and community-acquired infections like lobar pneumonia. This infection causes acute inflammation in the lung, characterized by the recruitment of polymorphonuclear cells, generating free radicals, and decreasing the endogenous antioxidant balance system. Many experimental studies have focused on the induction, progression and resolution of infection up to its peak, but these documented processes remain highly random and their sex dependence un-elicited. These fluctuations of physiopathological parameters would impact disease progression depending on the animal's model and bacterial strain used. The present study investigated the sex-dependent vulnerability of Wistar rats to K. pneumoniae ATCC 43816 lobar pneumonia induced by the intranasal instillation method. METHODS: Experimental pneumonia was induced by K. pneumoniae ATCC 43816 in male and female Wistar rats following intranasal instillation. The physiopathogenesis of the disease was studied by bacteriological and histopathological exams, histomorphometric analysis of the blood and/or lung tissue, and body weight loss in infected animals. In addition, the overall severity of lesions was determined by the total score obtained by averaging the individual scores from the same group of animals. RESULTS: The K. pneumoniae ATCC 43816 strain showed inoculation dose-, incubation time of the disease- and sex-dependent- differences in its ability to induce lobar pneumonia. Evaluation of different parameters showed that the disease peaked on day 15 post-inoculation, with more pathogenic effects on female rats. This observed sex-dependence difference in Wistar rats was mainly highlighted by the determined lethal dose 50 (LD50), bacterial load count in whole blood and lung tissues, body weight loss, inflammatory granulomas forming and diffuse alveolar damages. The pathogenicity was confirmed by scoring the severity of pathologic lesions of lung tissues. CONCLUSIONS: The results obtained highlighted the gender-dependency in the physiopathogenesis processes of K. pneumoniae ATCC 43816 induced-lobar pneumonia, in Wistar rats. Female Wistar rats' susceptibility is useful in studying pathology and in preclinical trial investigations of new treatments for infectious pneumonia.

Exploring the Efficacy of Musa Cavendish Stem Extract (Mucase) as a Novel Wound Dressing: A Comparative Study With Sofratulle®.

Background This investigation explores the wound-healing potential of Musa Cavendish banana components. Specifically, the Musa Cavendish stem extract (MUCASE), comparatively assessing its efficacy against the commercial conventional wound dressing Sofratulle® as a sterile gauze containing the antibiotic framycetin sulfate BP 1%, designed for accelerating wound healing. While Musa Cavendish banana components have been acknowledged for their topical applications, scarce research has scrutinized the specific impact of MUCASE as a wound dressing, especially concerning its comparison with Sofratulle®. Purpose The primary objective is to evaluate and compare the effectiveness of Sofratulle® and varied concentrations of MUCASE in managing incision wounds. Materials and methods Fifteen male Rattus norvegicus rats were randomly allocated into five groups, each subjected to distinct treatments: 40%, 20%, 10% MUCASE, Sofratulle®, and negative control. Over a seven-day treatment span, measurements of the exudation along with the incision wounds' surface area and the rate of wound contraction were conducted. Result The findings revealed significant differences in wound conditions within each group pre- and post-dressing application, except for the negative control and MUCASE 10% groups. Particularly, MUCASE 10% exhibited suboptimal outcomes compared to MUCASE 40%, 20%, and Sofratulle®, showcasing a non-significant ratio of wound healing (p > 0.05). A comparable potential was exhibited by MUCASE 40%, 20%, and Sofratulle® in accelerating the healing of incisional wounds. Conclusion Both Sofratulle® and MUCASE are deemed suitable as wound dressings to facilitate efficient and swift wound healing. Nevertheless, the study's outcomes suggest that MUCASE surpasses Sofratulle® in accelerating the healing process of wounds.

Studies on the Effect of Piperine on Hepatocyte Nuclear Factor 1 Alpha (HNF-1α) and Sterol Regulatory Element-Binding Protein 1c (SREBP-1c) Levels in High-Fat-Diet and Sucrose-Induced Type 2 Diabetes Mellitus Rats.

BACKGROUND: Piperine, a naturally occurring compound in black pepper (Piper nigrum), is known for its potential health benefits, including its reported enhancement of insulin sensitivity. However, the precise impact of piperine on hepatocyte nuclear factor 1 alpha (HNF-1α) and sterol regulatory element-binding protein 1c (SREBP-1c), transcription factors for insulin signaling and glucose metabolism in hepatocytes, remains unclear. OBJECTIVE: This study aims to investigate the effect of piperine, compared to metformin, on blood glucose and insulin levels by modifying the expression of hepatic HNF-1α and SREBP-1c in high-fat-diet (HFD) and sucrose-induced type 2 diabetes mellitus (T2DM) rats and in human Chang liver cells. METHODS: Adult male albino rats were categorized into four groups: group 1 as the control, group 2 as T2DM, group 3 as T2DM rats treated with piperine (40 mg), and group 4 as T2DM rats treated with metformin (50 mg). Fasting blood glucose (FBG) and serum insulin levels were measured using enzyme-linked immunosorbent assay (ELISA), while real-time polymerase chain reaction (RT-PCR) analysis was conducted to assess the mRNA expression of HNF-1α and SREBP-1c. Further, piperine was treated with normal and high glucose-induced Chang liver cells, and gene expression was analysed. Data analysis was performed using one-way analysis of variance (ANOVA), with a significance set at p<0.05. RESULTS: Treatment with piperine led to a notable decrease in blood glucose levels and circulating insulin when compared with T2DM rats (group 2). Additionally, piperine administration resulted in the upregulation of HNF-1α mRNA expression and downregulation of SREBP-1c mRNA levels whose effects were found to be near that of the control and standard drug metformin's effects. In vitro study also confirmed that piperine improved the HNF-1α expression and reduced the expression of SREBP-1c in Chang liver cells. CONCLUSION: Our findings suggest that piperine treatment effectively regulates hyperglycemic and hyperinsulinemic insulin resistance in the liver by modulating the expression of HNF-1α and SREBP-1c. Consequently, piperine emerges as a promising candidate for therapeutic intervention in managing T2DM.

Chronic mild stress-induced dysregulation of MAPK and PI3K/AKT signaling in the hippocampus and medial prefrontal cortex of WKY female rats.

Wistar-Kyoto (WKY) rats subjected to chronic mild stress (CMS) represent a valid model of treatment-resistant depression (TRD). Considering that depression is more prevalent in women than in men, in the present study, female rats were used. We investigated the effect of CMS on behavior and different factors involved in neuroinflammatory processes and neuroplasticity in the hippocampus and medial prefrontal cortex (mPFC) of WKY female rats. The results show that unstressed WKY females exhibited hypolocomotion, decreased exploratory behavior, and an increase in the total grooming time. After exposure to CMS, WKY females displayed intensified grooming. To investigate potential neural mechanisms underlying these behavioral changes, we analyzed signaling and inflammatory pathways in the hippocampus and mPFC. The findings indicate reduced BDNF and elevated levels levels of IL-1ß in both brain structures and NLRP3 in the mPFC of unstressed WKY female rats. WKY rats subjected to CMS showed a further decrease in BDNF levels and increased IL-1ß and NLRP3 in these brain structures. WKY showed reduced pERK1/2 and increased pp38 levels in both brain structures, while CMS revealed a further increase of pp38 in WKY in these brain structures. Expressions of p110ß and pAKT were decreased in the hippocampus and mPFC of WKY rats. The CMS further suppressed p110 and the downstream AKT phosphorylation in the hippocampus, but did not affect the p110 and pAKT in the mPFC. Our findings indicate behavioral and molecular differences in genetically vulnerable WKY female rats and in their response to CMS that may be involved in TRD.

Subchronic exposure to fenpyroximate causes multiorgan toxicity in Wistar rats by disrupting lipid profile, inducing oxidative stress and DNA damage.

BACKGROUND: Fenpyroximate (FEN) is an acaricide that inhibits the complex I of the mitochondrial respiratory chain in mites. Data concerning mammalian toxicity of this acaricide are limited; thus the aim of this work was to explore FEN toxicity on Wistar rats, particularly on cardiac, pulmonary, and splenic tissues and in bone marrow cells. METHODS: rats were treated orally with FEN at 1, 2, 4, and 8 mg/Kg bw for 28 days. After treatment, we analyzed lipid profile, oxidative stress and DNA damage in rat tissues. RESULTS: FEN exposure increased creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities, elevated total cholesterol (T-CHOL), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) concentrations, while decreasing high-density lipoprotein cholesterol (HDL-C). It inhibited acetylcholinesterase (AChE) activity, enhanced lipid peroxidation, protein oxidation, and modulated antioxidant enzymes activities (superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase). Comet assay indicated that FEN induced a dose-dependent DNA damage, contrasting with the micronucleus test showing no micronuclei formation. Nonetheless, FEN exhibited cytotoxicity to bone marrow cells, as evidenced by a reduction in the number of immature erythrocytes among total cells. CONCLUSION: FEN appears to carry out its genotoxic and cytotoxic activities most likely through an indirect pathway that involves oxidative stress.

Gelatine nanoparticles encapsulating three edible plant extracts as potential nanonutraceutical agents against type 2 diabetes mellitus.

AIM: To optimise, and characterise gelatine nanoparticles (GNPs) encapsulating plant extracts and evaluate the glucose-lowering potential. METHODS: GNPs encapsulating plant extracts were prepared by desolvation method followed by adsorption. The GNPs were characterised by loading efficiency, loading capacity, particle size, zeta potential, SEM and FTIR. The glucose-lowering activity of GNPs was determined using oral glucose tolerance test in high-fat diet fed streptozotocin-induced Wistar rats. RESULTS: Loading efficiency and capacity, particle mean diameter, and zeta potential of optimised GNPs 72.45 ± 13.03% w/w, 53.05 ± 26.16% w/w, 517 ± 48 nm and (-)23.43 ± 9.96 mV respectively. GNPs encapsulating aqueous extracts of C. grandis, S. auriculata, and ethanol 70% v/v extracts of M. koenigii showed glucose-lowering activity by 17.62%, 11.96% and 13.73% (p < 0.05) compared to the non-encapsulated extracts. FTIR analysis confirmed the encapsulation of phytoconstituents into GNPs. SEM imaging showed spherical GNPs (174 ± 46 nm). CONCLUSION: GNPs encapsulating plant extracts show promising potential to be developed as nanonutraceuticals against diabetes.

Anti-apoptotic and antioxidant mechanisms may underlie the abrogative potential of Ocimum gratissimum Linn. Leaf extract and fractions against trastuzumab-induced cardiotoxicity in Wistar rats.

Clinical use of trastuzumab (TZM), has been widely associated with increased incidence of cardiotoxicity. Ocimum gratissimum Linn. is a household medicinal plant popularly used for treating inflammatory conditions. In this study, we investigated the abrogative potential of 100 mg/kg/day of the ethanol leaf extract of Ocimum gratissimum Linn. (OG) and its petroleum ether (PEOG), ethyl acetate (EAOG) and ethanol (EOG) fractions in TZM intoxicated Wistar rats for 7 days using anthropometric, biochemical, histopathological and immunohistochemical endpoints. In addition, secondary metabolite constituents in OG and its fractions were determined through Gas Chromatography-Mass Spectrometry (GC-MS). The study results showed that oral pretreatments with OG and OG fractions as well as the fixed dose valsartan-lisinopril (VAL-LSP) combination effectively ameliorated and restore nearly normal levels the TZM-altered plasma cardiac troponin I and antioxidant profile which were corroborated by histopathological and immunohistochemical findings as indicated by the inhibition of TZM-induced activation of caspases-3 and - 9 and profound upregulation of BCL-2 expression. Phytoscan of OG and its fractions showed the presence of thymol and in high amount. Overall, our findings revealed the cardioprotective potentials of OG, OG fractions and fixed dose VAL-LSP combination against TZM-induced cardiotoxicity which probably was mediated via abrogation of cardiomyocyte apoptosis and antioxidant mechanisms.

The bone morphogenetic protein 2 analogue L51P enhances spinal fusion in combination with BMP2 in an in vivo rat tail model.

Bone morphogenic protein 2 (BMP2) is known to induce osteogenesis and is applied clinically to enhance spinal fusion despite adverse effects. BMP2 needs to be used in high doses to be effective due to the presence of BMP2 inhibitors. L51P is a BMP2 analogue that acts by inhibition of BMP2 inhibitors. Here, we hypothesized that mixtures of BMP2 and L51P could achieve better spinal fusion outcomes regarding ossification. To test whether mixtures of both cytokines are sufficient to improve ossification, 45 elderly Wistar rats (of which 21 were males) were assigned to seven experimental groups, all which received spinal fusion surgery, including discectomy at the caudal 4-5 level using an external fixator and a porous ß-tricalcium phosphate (ßTCP) carrier. These ßTCP carriers were coated with varying concentrations of BMP2 and L51P. X-rays were taken immediately after surgery and again six and twelve weeks post-operatively. Histological sections and µCT were analyzed after twelve weeks. Spinal fusion was assessed using X-ray, µCT and histology according to the Bridwell scale by voxel-based quantification and a semi-quantitative histological score, respectively. The results were congruent across modalities and revealed high ossification for high-dose BMP2 (10 µg), while PBS induced no ossification. Low-dose BMP2 (1 µg) or 10 µg L51P alone did not induce relevant bone formation. However, all combinations of low-dose BMP2 with L51P (1 µg + 1/5/10 µg) were able to induce similar ossificationas high-dose BMP2. These results are of high clinical relevance, as they indicate L51P is sufficient to increase the efficacy of BMP2 and thus lower the required dose for spinal fusion. STATEMENT OF SIGNIFICANCE: Spinal fusion surgery is frequently applied to treat spinal pathologies. Bone Morphogenic Protein-2 (BMP2) has been approved by the U .S. Food and Drug Administration (FDA-) and by the "Conformité Européenne" (CE)-label. However, its application is expensive and high concentrations cause side-effects. This research targets the improvement of the efficacy of BMP2 in spinal fusion surgery.