Control Rats Research Articles

Reductive stress in mitochondria isolated from the carotid body of type 1 diabetic male Wistar rats.

The carotid body (CB) senses changes in arterial O2 partial pressure (pO2) and glucose levels; therefore, it is key for the detection of hypoxia and hypoglycemia. The CB has been suggested to detect pO2 through an increase in reactive oxygen species (ROS) in the mitochondria. However, the mechanism protecting the chemoreceptor cells and their mitochondria from ROS and hyperglycemia is poorly understood. Here we measured glutathione levels in CB mitochondria of control and in streptozotocin (STZ)-induced type 1 diabetic male Wistar rats. We found a dramatic reduction in total glutathione from 11.45 ± 1.30 μmol/mg protein in control rats to 1.45 ± 0.31 μmol/mg protein in diabetic rats. However, the ratio of reduced to oxidized glutathione, a measure of the redox index, was increased in diabetic rats compared to controls. We conclude that the mitochondria of CB chemoreceptor cells in type 1 diabetic male Wistar rats were likely under glutathione-reducing stress.

Transcriptomic Analysis of Cardiac Tissues in a Rodent Model of Coronary Microembolization.

Coronary microembolization (CME) can result in cardiac dysfunction, severe arrhythmias, and a reduced coronary flow reserve. Impairment of mitochondrial energy metabolism has been implicated in the progression and pathogenesis of CME; however, its role remains largely undetermined. This study aimed to explore alterations in mitochondria-related genes in CME. A rat model of CME was successfully established by injecting plastic microspheres into the left ventricle. The cardiac tissues of the two groups were sequenced and mitochondrial functions were assessed. Using RNA-Seq, together with GO and KEGG enrichment analyses, we identified 3822 differentially expressed genes (DEGs) in CME rats compared to control rats, and 101 DEGs were mitochondria-related genes. Notably, 36 DEGs were up-regulated and 65 DEGs were down-regulated (CME vs control). In particular, the oxidative phosphorylation (OXPHOS) and mitochondrial electron transport were obviously down-regulated in the CME group. Functional analysis revealed that CME mice exhibited marked reductions in ATP and mitochondrial membrane potential (MMP), by contrast, the production of reactive oxygen species (ROS) was much higher in CME mice than in controls. Protein-protein interaction (PPI) and quantitative PCR (qPCR) validation suggested that eight hub genes including Cmpk2, Isg15, Acsl1, Etfb, Ndufa8, Adhfe1, Gabarapl1 and Acot13 were down-regulated in CME, whereas Aldh18a1 and Hspa5 were up-regulated. Our findings suggest that dysfunctions in mitochondrial activity and metabolism are important mechanisms for CME, and mitochondria-related DEGs may be potential therapeutic targets for CME.

Ethanolic extract of Ficus religiosa leaves alleviates aluminum-induced oxidative stress, lipid peroxidation, and neuroinflammation in rat brain.

Aluminum (Al)-induced neurotoxicity is known to play a pivotal role in the development of various neurodegenerative diseases, and this is alleged to occur through neuroinflammation and oxidative stress in the brain. This study aimed to determine the effect of Ficus religiosa (FR) leaf extract on oxidative stress and neuroinflammation induced by Al exposure in the rat brain by estimating malondialdehyde (MDA), interleukin-6 (IL6), and total antioxidant (TAO) levels along with the degree of neurodegeneration in the brain of AlCl3-administered and FR leaf extract-treated rats. Two- to three-month-old male albino Wistar rats weighing 250-280 g were used in the present study. The animals were randomly divided into seven groups, with 12 rats in each group. The groups were categorized as control, Al-intoxicated, FR treatment groups of two dosages, FR control rats of two dosages, and FR pre-treatment group. We observed a substantial increase in the levels of MDA and IL6 along with a decline in the TAO level in Al-intoxicated rats, suggesting increased lipid peroxidation (LPO), neuroinflammation, and oxidative stress, respectively. In the FR-treated animals, MDA as well as IL6 levels was decreased, and TAO was enhanced in addition to improved neuronal architecture, demonstrating the ameliorative effect of FR. The present study observed a decline in LPO and neuroinflammation in FR-treated rats, demonstrating the protective effect of FR leaves against Al-induced neurotoxicity. The level of TAO also improved along with improvement in neuronal mass in FR-treated rats, adding to its ameliorative effect. However, further elaborate research is needed to confirm its therapeutic potential against inflammation-driven neurodegenerative diseases.

Unveiling the antiurolithiatic potentiality of two benzene sulfonamide derivatives against ethylene glycol-induced renal calculi

ObjectiveOxidative stress and inflammation play crucial roles in the onset of kidney injury and crystal formation caused by hyperoxaluria. Indapamide is a potent medication for treating renal calculi, but it has severe side effects such as hypokalemia, hypercalcemia, and hyperuricemia. Therefore, it is advisable to explore alternative treatments that do not have these side effects. The study aimed to reveal the antiurolithiatic potential of two benzene sulfonamide derivatives (SBCl and SBF; A and B, respectively) against ethylene glycol-induced kidney stones. MethodsThe rats were divided into two main groups: the first group consisted of 20 rats with induced kidney stones, and the second group included 15 control rats. This division enabled a comparative analysis between rats with kidney stones and those without, offering insights into the effects of kidney stone induction on various physiological parameters and biochemical markers. The effectiveness of benzene sulfonamide derivatives (compounds A and B) was assessed in rats with induced kidney stones. The treatment was given orally by gavage for 21 days, administered every 48h after inducing kidney stones with 0.12ml of 5% ethylene glycol (EG). ResultsThe influence of compounds A and B on electrolytes, biochemical, antioxidant, and inflammatory reactions in induced kidneys underscores their potential therapeutic advantages in alleviating the advancement of kidney stone disease and related complications. ConclusionBoth compounds were found to possess equal effectiveness in inhibiting the complications of stone formation. However, SBCl-EG showed superior antioxidant and inflammatory parameters effects compared to SBF-EG. Our study's findings underscore the potential benefits of derivatives in treating nephrolithiasis and related oxidative disorders, highlighting their superior effects on antioxidant and inflammatory responses compared to standard treatments.

Inhibition of Soluble Epoxide Hydrolase Ameliorates Cerebral Blood Flow Autoregulation and Cognition in Alzheimer's Disease and Diabetes-Related Dementia Rat Models.

Alzheimer's Disease and Alzheimer's Disease-related dementias (AD/ADRD) pose major global healthcare challenges, with diabetes mellitus (DM) being a key risk factor. Both AD and DM-related ADRD are characterized by reduced cerebral blood flow, although the exact mechanisms remain unclear. We previously identified compromised cerebral hemodynamics as early signs in TgF344-AD and type 2 DM-ADRD (T2DN) rat models. Genome-wide studies have linked AD/ADRD to SNPs in soluble epoxide hydrolase (sEH). This study explored the effects of sEH inhibition with TPPU on cerebral vascular function and cognition in AD and DM-ADRD models. Chronic TPPU treatment improved cognition in both AD and DM-ADRD rats without affecting body weight. In DM-ADRD rats, TPPU reduced plasma glucose and HbA1C levels. Transcriptomic analysis of primary cerebral vascular smooth muscle cells from AD rats treated with TPPU revealed enhanced pathways related to cell contraction, alongside decreased oxidative stress and inflammation. Both AD and DM-ADRD rats exhibited impaired myogenic responses and autoregulation in the cerebral circulation, which were normalized with chronic sEH inhibition. Additionally, TPPU improved acetylcholine-induced vasodilation in the middle cerebral arteries (MCA) of DM-ADRD rats. Acute TPPU administration unexpectedly caused vasoconstriction in the MCA of DM-ADRD rats at lower doses. In contrast, higher doses or longer durations were required to induce effective vasodilation at physiological perfusion pressure in both control and ADRD rats. Additionally, TPPU decreased reactive oxygen species production in cerebral vessels of AD and DM-ADRD rats. These findings provide novel evidence that chronic sEH inhibition can reverse cerebrovascular dysfunction and cognitive impairments in AD/ADRD, offering a promising avenue for therapeutic development.

Continuous exercise training rescues hippocampal long-term potentiation in the VPA rat model of Autism: Uncovering sex-specific effects

Long‐term potentiation (LTP) impairment has been reported in many studies of autistic models. The aim of the present study was to investigate the effects of interval training (IT) and continuous training (CT) exercises on LTP in the hippocampal dentate gyrus (DG) neurons of valproic acid (VPA) rat model of autism. To induce an autism-like model, pregnant rats were injected 500 mg/kg NaVPA (intraperitoneal) on the embryonic day 12.5. IT and CT aerobic exercises started on postnatal day 56 in the offspring. Four weeks after IT and/or CT exercises, the offspring were urethane-anesthetized and placed into a stereotaxic apparatus for surgery, electrode implantation, and field potential recording. In the DG region, excitatory post synaptic potentials (EPSP) slope and population spike (PS) amplitude were measured. Sex differences in LTP were evident for control rats but not for VPA-exposed offspring. LTP was significantly smaller in VPA-exposed male offspring compared with control male rats. In contrast to males, there was no difference between VPA-exposed female offspring and control female rats. Interestingly, we observed a sex difference in the response to exercise between VPA-exposed male and female offspring. CT exercise training (but not IT) increased LTP in VPA-exposed male offspring. Both IT and CT exercise trainings had no effect on intact LTP in VPA-exposed female offspring. Our work suggests that there may be differences in the benefits of exercise interventions based on sex, and CT exercise training could be more beneficial for LTP improvements.

Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats.

Adolescent cannabis use is linked to later-life changes in cognition, learning, and memory. Rodent experimental studies suggest Δ9-tetrahydrocannabinol (THC) influences development of circuits underlying these processes, especially in the prefrontal cortex, which matures during adolescence. We determined how 14 daily THC injections (5mg/kg) during adolescence persistently impacts medial prefrontal cortex (mPFC) dopamine-dependent cognition. In adult Long Evans rats treated as adolescents with THC (AdoTHC), we quantify performance on two mPFC dopamine-dependent reward-based tasks-strategy set shifting and probabilistic discounting. We also determined how acute dopamine augmentation with amphetamine (0, 0.25, 0.5mg/kg), or specific chemogenetic stimulation of ventral tegmental area (VTA) dopamine neurons and their projections to mPFC impact probabilistic discounting. AdoTHC sex-dependently impacts acquisition of cue-guided instrumental reward seeking, but has minimal effects on set-shifting or probabilistic discounting in either sex. When we challenged dopamine circuits acutely with amphetamine during probabilistic discounting, we found reduced discounting of improbable reward options, with AdoTHC rats being more sensitive to these effects than controls. In contrast, neither acute chemogenetic stimulation of VTA dopamine neurons nor pathway-specific chemogenetic stimulation of their projection to mPFC impacted probabilistic discounting in control rats, although stimulation of this cortical dopamine projection slightly disrupted choices in AdoTHC rats. These studies confirm a marked specificity in the cognitive processes impacted by AdoTHC exposure. They also suggest that some persistent AdoTHC effects may alter amphetamine-induced cognitive changes in a manner independent of VTA dopamine neurons or their projections to mPFC.

Chitosan-collagen biopolymer biofilm derived from cephalopod gladius; Evaluation of osteogenesis, angiogenesis and wound healing for tissue engineering application

Chitosan (Ch) and acid-soluble collagen (ASC) from Doryteuthis singhalensis gladius were isolated to test their osteogenic, angiogenic, and wound healing capabilities in male Wistar rats. The results of the study showed that the ASC yield was 18.58 %, the total protein content was 86.43 % ± 0.18 %, and the amino acid composition was as follows: glycine, 15.68 %; proline, 13.84 %. A, B, I, II, and III show FT-IR amide regional bands at 3392, 2959, 1652, 1471, and 1237 cm−1 respectively. The electrophoretic pattern of ASC validated its molecular weights of 105 kDa and 96 kDa. The 1H NMR spectra showed pure singles at 1.99 ppm, and the UV–Vis spectrum showed a particular absorbance between 238 and 220 nm. The DSC showed two endothermic peaks: one with an To value of 119.72 °C and TP of 126.28 °C, and the other with 147.42 °C and 148.47 °C. Initially, we fabricated Ch and ASC biofilms at an 8.5:1.5 ratio for tissue engineering applications. A cellular-level study demonstrated good biocompatibility and enhanced osteoblastic differentiation of collagen chitosan films (CChF). Additionally, the biofilm exhibited increased angiogenic potency, as observed in the chick embryo chorioallantoic membrane (CAM) assay. The experimental animal model demonstrated that in wound healing, the CChF treated rats (95.75 ± 2.28 %) had a greater decrease in the diameter of the wound than the control rats (22.25 ± 2.45 %), followed by the CF (collagen film) treated rats (63.25 ± 2.08 %) and ChF (chitosan film) (52.67 ± 1.58 %). Rats treated with CChF had 48.82 ± 1.25 mg/g of hydroxyproline in NFGT and 75.25 ± 1.56 mg/g of overall protein. The higher hydroxyproline levels in the CChF-treated groups corroborated these histopathological findings. These results imply that by promoting the development of scars, inflammation, and proliferation, CChF accelerates the healing process.

Evaluation of Low-Dose Effects and Non-Monotonous Dose Response of Butyl p-hydroxybenzoate, or Butylparaben on Female Wistar Rats

Butylparaben (BP) is an extensively used synthetic preservative that has been testified as an endocrine disruptor and speculated to be toxic for the body all together. The present study evaluated the possible noxious impact of BP at minimum doses, i.e., 1, 5, and 10 mg/kg BW/day, on female Wistar rats following consecutive subcutaneous exposure for 7 and 21 days. The results of the genotoxic study exhibited that BP at a dose of 10 mg/kg BW/day significantly (p ˂ 0.05) induced micronucleated polychromatic erythrocytes (MNPCEs) formation in bone marrow of rats, both in short (7.3 ± 0.87 MNPCEs/1000 PCEs) and long-term exposures (6.6 ± 0.33 MNPCEs/1000 PCEs), which was in line with the results obtained for 17β-estradiol (E2)-treated reference control rats. Levels of hepatic toxicity marker enzymes, i.e., aspartate transaminase (AST) and alanine transaminase (ALT), were not altered substantially in any of the study durations, but the alkaline phosphatase (ALP) level increased significantly (p ˂ 0.05) at all BP doses, including E2. Variations in the serum HDL as well as cholesterol levels were found to be non-monotonous with respect to the applied BP doses. However, contrasting specifics were observed for triglycerides in terms of the study durations. Conclusively, the current study established that BP, even at low doses, could evidently disturb the circulating lipid content, hepatic enzyme levels, and even cause genotoxicity, and also pointed toward its non-monotonous dose response.

BMP2 Diminishes Angiotensin II-Induced Atrial Fibrillation by Inhibiting NLRP3 Inflammasome Signaling in Atrial Fibroblasts.

Atrial fibrillation (AF) is the most common sustained arrhythmia to affect 1% of the global population and increases with age. Atrial fibrosis is a crucial substrate for promoting structural remodeling to cause atrial arrhythmogenesis. Bone morphogenic protein 2 (BMP2) has been reported to be involved in cardiac fibrogenesis. However, its role in modulating atrial fibrosis to affect AF development remains unknown. Our study aimed to investigate the expression of BMP2 under different AF conditions and the effect of BMP2 on the progression of atrial fibrosis using an angiotensin II (Ang II) rat model and an ex vivo cardiac fibroblast model. The qRT-PCR and Western blot assay showed increased BMP2 mRNA and protein levels in the atria of chronic AF patients and the right atria of a tachypacing rabbit model. In contrast, the levels of BMP2 receptor mRNA were comparable. The AF incidence of the Ang II rat was higher than that of a control rat, which was reduced by BMP2 treatment. Masson staining demonstrated an anti-fibrogenic impact on BMP2-subjected rat atria compared to only Ang II-treated rat atria. RNA-sequencing indicated the potential function of blocking NLRP3-associted inflammasome activation in BMP2-treated rat atrial tissues. In vitro, transfecting BMP2 shRNA into neonatal rat atrial fibroblasts upregulated the mRNA levels of NLRP3/Caspase-1/p20/ASC and the secretion of IL-1β and IL-6. In contrast, recombinant BMP2 protein attenuated the increased levels of the NLRP3 inflammasome pathway induced by Ang II. In summary, BMP2 opposes atrial fibrosis to alleviate AF susceptibility by inhibiting the activation of the inflammasome in atrial fibroblasts.

Leptin limits hepatic lipid accumulation and inflammation via vagal activation of the JAK2-STAT3/AMPK pathway

Non-Alcoholic Fatty Liver Disease (NAFLD) begins with hepatic lipid accumulation, and leptin has antisteatosis properties. In this study, we investigated the effects of leptin on hepatic steatosis and inflammation through the vagal pathway independently of the inhibitory effect of food intake. Male Sprague-Dawley rats were matched for food intake after the high-fat diet (HFD)-induced obesity model and were injected intraperitoneally with leptin or leptin + lidocaine for 6 weeks. Control rats received equal volumes of saline. Adipose tissue mass, NAFLD activity scores (NAS), hepatic inflammatory factors, hepatic triglyceride content and hepatic lipid metabolism-related protein levels were evaluated. Leptin ameliorated HFD-induced hepatic lipid accumulation, improved NAS, and decreased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) levels in the presence of matched intake. Lidocaine decreased the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) expression in the nucleus tractus solitarius (NTS) and abrogated the leptin-mediated improvement. Leptin increased hypothalamic phosphorylated Janus kinase 2 (p-JAK2) and p-STAT3 expression, as well as the expression of mitochondrial respiratory chain-related genes. Leptin also increased hepatic phosphorylated adenosine 5′-monophosphate-activated protein kinase (p-AMPK) expression and phosphorylation of its downstream target acetyl Co A carboxylase 1 (ACC1), reducing de novo lipogenesis. Our results suggest that leptin ameliorated hepatic lipid accumulation and inflammation by activating the JAK2-STAT3/AMPK pathway through the vagal pathway independently of the inhibitory effect of ingestion. Leptin has the potential to be a drug for early NAFLD treatment.

Recovery of ventilatory and metabolic responses to hypoxia in neonatal rats after chronic hypoxia

Chronic hypoxia (CH) during postnatal development attenuates the hypoxic ventilatory response (HVR) in mammals, but there are conflicting reports on whether this plasticity is permanent or reversible. This study tested the hypothesis that CH-induced respiratory plasticity is reversible in neonatal rats and investigated whether the initial plasticity or recovery differs between sexes. Rat pups were exposed to 3 d of normobaric CH (12 % O2) beginning shortly after birth. Ventilation and metabolic CO2 production were then measured in normoxia and during an acute hypoxic challenge (12 % O2) immediately following CH and after 1, 4–5, and 7 d in room air. CH pups hyperventilated when returned to normoxia immediately following CH, but normoxic ventilation was similar to age-matched control rats within 7 d after return to room air. The early phase of the HVR (minute 1) was only blunted immediately following the CH exposure, while the late phase of the HVR (minute 15) remained blunted after 1 and 4–5 d in room air; recovery appeared complete by 7 d. However, when normalized to CO2 production, the late phase of the hypoxic response recovered within only 1 d. The initial blunting of the HVR and subsequent recovery were similar in female and male rats. Carotid body responses to hypoxia (in vitro) were also normal in CH pups after approximately one week in room air. Collectively, these data indicate that ventilatory and metabolic responses to hypoxia recover rapidly in both female and male neonatal rats once normoxia is restored following CH.

NUMB attenuates posttraumatic osteoarthritis by inhibiting BTRC and inactivating the NF-κB pathway

Posttraumatic osteoarthritis (PTOA) is closely related to the inflammatory response caused by mechanical injury and leads to joint degeneration. Herein, we aimed to evaluate the role and underlying mechanism of NUMB in PTOA progression. Anterior cruciate ligament transection (ACLT)-induced rats and interleukin (IL)-1β-treated chondrocytes were used as in vivo and in vitro models of PTOA, respectively. The NUMB overexpression plasmid (pcDNA-NUMB) was administered by intra-articular injection to PTOA model rats, and safranin O-fast green staining, the Osteoarthritis Research Society International (OARSI) scoring system, and HE staining were used to evaluate the severity of cartilage damage. The secretion of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and chondrocyte-specific markers (MMP13 and COL2A1) was detected via ELISA. Cell viability and apoptosis were evaluated by MTT and TUNEL assays. NUMB was expressed at lower levels in ACLT-induced PTOA rats and in IL-1β-treated chondrocytes than in control rats and cells. NUMB overexpression enhanced cell viability and reduced cell apoptosis, inflammation and cartilage degradation in chondrocytes stimulated by IL-1β. NUMB bound to BTRC to promote p-IκBα expression, resulting in NF-κB pathway inactivation. BTRC overexpression reversed the promoting effect of NUMB overexpression on cell viability and the inhibitory effects of NUMB overexpression on apoptosis, inflammation and cartilage degradation in IL-1β-induced chondrocytes. In addition, overexpression of NUMB alleviated articular cartilage damage by repressing inflammation and cartilage degradation in ACLT-induced PTOA rats. Our data indicated that NUMB regulated PTOA progression through the BTRC/NF-κB pathway, which may be a viable therapeutic target in PTOA.

Comparison of nociceptor properties using electrophysiology in preclinical models of osteoarthritis

Osteoarthritis (OA) pain originates in the joint by sensitization of articular nociceptors. While behavioural assessments provide valuable information regarding pain symptoms, the techniques are subjective and open to interpretation by the experimenter. This study used in vivo electrophysiological approaches to measure objectively joint nociceptor properties in three rodent models of OA. Single unit extracellular recordings of joint mechanosensitive afferents were carried out in male and female rats following either (1) transection of the medial meniscus (MMT: post-traumatic OA), (2) intra-articular injection of sodium monoiodoacetate (MIA: chemically-induced OA), or (3) intra-articular injection of lysophosphatidic acid (LPA: neuropathic OA). In naïve male control rats, the mechanical threshold of joint mechanonociceptors (23.5 ± 1.8 mNm) was significantly reduced with MMT (9.4 ± 1.1 mNm) and MIA (15.1 ± 1.6 mNm). In females, the mechanical threshold of naïve rats (23.2 ± 3.1 mNm) was reduced following induction of MMT (8.3 ± 1.0 mNm) and LPA (10.6 ± 2.2 mNm). Afferent firing frequency increased in male MMT (∼275 %), LPA (∼175 %), MIA (225 %), and female MMT (∼146 %), LPA (∼200 %), and MIA (∼192 %). Mechanical threshold and evoked firing were negatively correlated in all models for both sexes except LPA rats (male + female) and female MMT. These data indicate that MMT, MIA, and LPA induce peripheral sensitization of joint afferents thereby validating their use in OA pain studies.

Intracerebroventricular insulin injection acutely normalizes the augmented exercise pressor reflex in male rats with type 2 diabetes mellitus.

The exercise pressor reflex (EPR) is exaggerated in type 2 diabetes mellitus (T2DM), but the underlying central nervous system aberrations have not been fully delineated. Stimulation of muscle afferents within working skeletal muscle activates the EPR, by sending information to neurons in the brainstem, where it is integrated and results in reflexively increased mean arterial pressure (MAP) and sympathetic nerve activity. Brain insulin is known to regulate neural activity within the brainstem. We hypothesize that brain insulin injection in T2DM rats attenuates the augmented EPR, and that T2DM is associated with decreased brain insulin. Using male Sprague-Dawley rats, T2DM and control rats were generated via an induction protocol with two low doses of streptozotocin (35 and 25mg/kg, i.p.) in combination with a 14-23-week high-fat diet or saline injections and a low-fat diet, respectively. After decerebration, MAP and renal sympathetic nerve activity (RSNA) were evaluated during EPR stimulation, evoked by electrically induced muscle contraction via ventral root stimulation, before and after (1 and 2h post) intracerebroventricular (i.c.v.) insulin microinjections (500mU, 50nl). i.c.v. insulin decreased peak MAP (ΔMAP Pre (36±14mmHg) vs. 1h (21±14mmHg) vs. 2h (11±6mmHg), P<0.05) and RSNA (ΔRSNA Pre (107.5±40%), vs. 1h (75.4±46%) vs. 2h (51±35%), P<0.05) responses in T2DM, but not controls. In T2DM rats, cerebrospinal fluid insulin was decreased (0.41±0.19 vs. 0.11±0.05ng/ml, control (n=14) vs. T2DM (n=4), P<0.01). The results demonstrated that insulin injections into the brain normalized the augmented EPR in brain hypoinsulinaemic T2DM rats, indicating that the EPR can be regulated by brain insulin. KEY POINTS: The reflexive increase in blood pressure and sympathetic nerve activity mediated by the autonomic nervous system during muscle contractions is also known as the exercise pressor reflex. The exercise pressor reflex is dangerously augmented in type 2 diabetes, in both rats and humans. In type 2 diabetic rats both cerebrospinal fluid insulin and phosphoinositide 3-kinase signalling within cardiovascular brainstem neurons decrease in parallel. Brain insulin injections decrease the magnitude of the reflexive pressor and sympathetic responses to hindlimb muscle contraction in type 2 diabetic rats. Partial correction of low insulin within the central nervous system in type 2 diabetes may treat aberrant exercise pressor reflex function.

Effect of a Triterpenoid-Rich Olive Oil on Chronic Kidney Disease in an Experimental Model of Diabetes Mellitus.

The aim of this study was to assess the effect of triterpenoids on the development of diabetic nephropathy in an experimental model of diabetes mellitus. For this purpose, a destoned and dehydrated olive oil (DDOO) was used, comparing its effects to a destoned olive oil (DOO). DDOO had a higher triterpenoid content than DOO but an equal content of alcoholic polyphenols. Four study groups (n = 10 animals/group) were formed: healthy rats, diabetic control rats (DRs), and DRs treated orally with 0.5 mL/kg/day of DOO or DDOO for two months. DRs showed impaired renal function (proteinuria, increased serum creatinine, decreased renal creatinine clearance) and morphology (glomerular volume and glomerulosclerosis). These alterations correlated with increased systemic and renal tissue oxidative stress and decreased prostacyclin production. DDOO administration significantly reduced all variables of renal damage, as well as systemic and renal oxidative stress, to a greater extent than the effect produced by DOO. In conclusion, triterpenoid-rich olive oil may prevent kidney damage in experimental diabetes mellitus.

Brazil nut (Bertholletia excelsa) and metformin abrogate cardiac complication in fructose/STZ-induced type 2 diabetic rats by attenuating oxidative stress and modulating the MAPK-mTOR/NFkB/IL-10 signaling pathways.

The global prevalence of diabetic heart complication has been on the increase, and some of the drugs that are currently used to treat diabetes mellitus (DM) have not been able to mitigate this complication. This study determines the effect of Brazil nut (Bertholletia excelsa) and metformin on diabetic cardiomyopathy (DCM) in fructose/streptozotocin (STZ)-induced type 2 diabetic rats and also characterizes using Gas Chromatography Mass Spectrophotometry and Fourier Transform Infrared the bioactive compounds in 50% aqueous ethanol extract of Brazil nut. After inducing type 2 DM, 30 male albino Wistar rats were separated into five groups that comprised of six rats per group, and they were treated as follows: groups 1 (Control) and 2 (Diabetic control) rats received rat pellets and distilled water; group 3 (Diabetic + Brazil nut) received rat pellets and Brazil nut extract (100 mg/kg, orally) dissolved in distilled water, group 4 (Diabetic + metformin) received metformin (100 mg/kg, orally) dissolved in distilled water, while group 5 (Diabetic + Brazil nut + metformin) received oral administrations of Brazil nut (100 mg/kg) and metformin (100 mg/kg) dissolved in distilled water. This study lasted for 6 weeks. The dose of Brazil nut used was selected from our pilot study on the minimum therapeutic dose of different concentrations of Brazil nut extract. STZ administration induced insulin resistance, hyperglycemia, loss of weight, dyslipidemia, oxidative stress, inflammation, apoptosis, alteration of mammalian target of rapamycin, mitogen-activated protein kinase, heart function markers (creatine kinase MB, lactate dehydrogenase, and aspartate amino transaminase), and heart histology of the diabetic control, which was ameliorated after treatment with Brazil nut and metformin, but their combined treatment was better than the single treatments. This study shows that Brazil nut contains several bioactive compounds that support its biological properties as well as its candidature as a complementary therapy to metformin in mitigating cardiac complications arising from DM in rats.

GDNF's Role in Mitigating Intestinal Reactive Gliosis and Inflammation to Improve Constipation and Depressive Behavior in Rats with Parkinson's disease.

Constipation is a common symptom in patients with Parkinson's disease (PD) and is often associated with depression. Enteric glial cells (EGCs) are crucial for regulating intestinal inflammation and colon motility, and their activation can lead to the death of intestinal neurons. Glial cell line-derived neurotrophic factor (GDNF) has been recognized for its neuroprotective properties in various neurological disorders, including PD. This study explores the potential of GDNF in alleviating intestinal reactive gliosis and inflammation, thereby improving constipation and depressive behavior in a rat model of PD.A PD model was established via unilateral stereotaxic injection of 6-hydroxydopamine (6-OHDA). Five weeks post-injury, AAV5-GDNF (2 ~ 5 × 10^11) was intraperitoneally injected into experimental and control rats. Fecal moisture percentage (FMP) and colonic propulsion rate (CPPR) were used to evaluate colon motility. Colon-related inflammation and colonic epithelial morphology were assessed, and depressive behavior was analyzed one week before sampling.PD rats exhibited reduced colonic motility and GDNF expression, along with increased EGC reactivity and elevated levels of pro-inflammatory cytokines IL-1, IL-6, and TNF-α. Additionally, there was an up-regulation of CX43 and a decrease in PGP 9.5 expression. The intraperitoneal injection of AAV-GDNF significantly protected colonic neurons by inhibiting EGC activation and down-regulating CX43. This treatment also led to a notable reduction in depressive-like symptoms in PD rats with constipation.GDNF effectively reduces markers of reactive gliosis and inflammation, and promotes the survival of colonic neurons, and improves colonic motility in PD rats by regulating CX43 activity. Furthermore, GDNF treatment alleviates depressive behavior, suggesting that GDNF or its agonists could be promising therapeutic agents for managing gastrointestinal and neuropsychiatric symptoms associated with PD.

Effects of the Aquatic Extract of Cinnamon Zeylanicum on STZ-Induced Diabetic Rats: A Molecular and Histopathological Study

Background: The prevalence of diabetes mellitus has increased over the past few decades, making it a significant public health challenge of the twenty-first century. Cinnamon, as a traditional medicine, has been used in several regions of the world for its anti-diabetic properties. Objectives: The current study was conducted to determine the effect of Cinnamon Zeylanicum extract on blood glucose levels, oxidative stress markers, and antioxidant enzyme gene expression in diabetic rats. Methods: Forty Sprague-Dawley rats were divided into four groups, each containing 10 rats. A single dose of streptozotocin (50 mg/kg, IP) was used to induce diabetes. In this investigation, 40 mg/kg body weight of cinnamon extract was administered orally. After eight weeks, the levels of glucose, malondialdehyde (MDA), and reduced glutathione (GSH) were determined using biochemical methods. Additionally, the expression levels of catalase and glutathione reductase in the rat liver homogenate were evaluated using real-time PCR. The effect of cinnamon extract on histopathological changes in the rats' liver was also investigated. Results: The findings indicated that the administration of cinnamon extract resulted in a considerable reduction in blood glucose (210 ± 29.9 vs. 449 ± 48.4 mg/dL; P &lt; 0.001) and liver MDA levels (2.01 ± 0.35 vs. 3.05 ± 0.47; P &lt; 0.001) in diabetic rats after eight weeks. However, this extract had no significant effect on GSH levels (4.71 ± 0.25 vs. 4.75 ± 0.42; P = 0.79) in diabetic rats compared to diabetic control rats. The mRNA expression of catalase and glutathione reductase genes in the liver of diabetic control rats (0.73 ± 0.23 and 0.90 ± 0.18, respectively) was significantly lower than that of the healthy control group (1.33 ± 0.37 and 1.46 ± 0.54, respectively) (P = 0.001, P = 0.012). Administration of cinnamon extract increased the expression levels of these antioxidant enzyme genes, but these changes were statistically not significant (P = 0.72 and P = 0.48, respectively). Furthermore, the creation of hyperglycemia led to slight hypertrophic degeneration and lymphocyte infiltration in hepatocytes. Notably, the administration of cinnamon extract was unable to reverse these abnormalities. Conclusions: The findings of our study support cinnamon's anti-diabetic and antioxidant properties in diabetic rats. However, the histological abnormalities in the diabetic rats' livers could not be altered by the administration of cinnamon.

Effects of Strawberry Tree Water Leaf Extract and Arbutin on Biochemical Markers and DNA Integrity in Brain Cells of Lewis Rats.

There is growing evidence that arbutin and plant extracts rich in arbutin, such as extracts of the strawberry tree (Arbutus unedo L.), exert a range of beneficial effects, including cyto- and genoprotective properties. This study evaluated the effects of strawberry tree water leaf extract (STE) and arbutin in the brain tissue of Lewis rats. STE or arbutin were administered per os to male and female rats at a dose of 200 mg/kg body weight/day for 14 or 28 days. Treatment outcomes were evaluated using biochemical markers (lipid peroxidation and the activities of the antioxidative enzymes catalase and superoxide dismutase). The effects of the tested substances on DNA integrity in brain cells were evaluated using the alkaline comet assay. The results suggest a high biocompatibility of both tested substances with rat brain tissue. No significant harmful disturbances were observed in the oxidative/antioxidative status or impairments of DNA integrity in the rat brain cells. Nearly all post-treatment values were within tolerable limits as compared to the matched control rats. Such encouraging findings support further research using other subtle biomarkers to clarify the safety aspects of arbutin and STE prior to the development of specific nutraceutical products.