Non-treated Rats Research Articles

Antidepressant effects of capsaicin in rats with chronic unpredictable mild stress-induced depression

Purpose: This study was conducted to assess the antidepressant effects of capsaicin in chronic depressive rats and elucidate the mechanism underlying its effects.Methods: Male Wistar rats (280~320 g, 8 weeks of age) were subjected to depression induced by chronic unpredictable mild stresses. The rats were exposed to 8 kinds of stresses for 8 weeks. In the last 2 weeks, fluoxetine or capsaicin was injected subcutaneously. The dose of fluoxetine was 10 mg/kg (body weight), while the doses of capsaicin consisted of low (1 mg/kg), middle (5 mg/kg), and high (10 mg/kg). The forced swim test (FST) was conducted to evaluate the immobility time of rats. The immobility time indicates despair, one of symptoms of depression. The change of tryptophan hydroxylase (TPH) in the dorsal raphe was investigated using immunohistochemistry. In the hippocampus cornu ammonis (CA) 1 and 3, glucocorticoid receptor (GR) expression was measured.Results: The immobility time in the FST was significantly lower (p < .05) in the low-dose (M = 32.40 ± 13.41 seconds) and middle-dose (M = 28.48 ± 19.57 seconds) groups than in the non-treated depressive rats (M = 90.19 ± 45.34 seconds). The amount of TPH in the dorsal raphe was significantly higher (p < .05) in the middle-dose (M = 249.17 ± 35.02) and high-dose (M = 251.0 ± 56.85) groups than in the non-treated depressive rats (M = 159.78 ± 41.16). However, GR expression in the hippocampus CA1 and CA3 did not show significant differences between the non-treated depressive rats and the capsaicin-injected rats.Conclusion: This study suggests that capsaicin produces an antidepressant-like effect on chronic unpredictable mild stress-induced depression in rats via the serotonin biosynthesis pathway.

Resveratrol Mitigates Diabetic Testicular Dysfunction, Endocrine Deficits, and Insulin Resistance via Suppression of Sperm-Endocrine Aberrations and Oxidative Inflammation in Rats

Diabetes mellitus (DM) provokes reproductive impairments through endocrine disturbance, sperm deficits, and testicular oxidative inflammation. The study investigated the reproductive protective effects of resveratrol (RSV) against testicular oxidative inflammation, sperm/endocrine deficits, and insulin resistance in streptozotocin- (STZ-, 65 mg/kg) induced DM rat model. Male rats were randomly divided into 4 groups ( n = 6 ): control, DM, RSV (150 mg/kg bw, orally), and RSV+DM group (21 days). The nontreated DM rats showed marked decreases in serum insulin, reproductive hormones (T, LH, and FSH), and lipid profile levels compared to control. The homeostatic index of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI) were adversely modulated. Sperm count and motility were profoundly decreased, whereas sperm abnormality was significantly increased. The testicular activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and malondialdehyde (MDA) level, along with inflammatory cytokines (TNF-α, IL-6, IL-4, and IL-10) were significantly dysregulated. The DM induced histopathological lesions compared to control rats. Interestingly, the RSV administration to DM rats attenuated the altered reproductive parameters, restored antioxidant mechanism, and anti-inflammatory responses with improved insulin resistance. RSV could prevent DM-induced reproductive deficits and insulin resistance via modulating oxidative stress-mediated testicular inflammation in rats.

The Comparison of Normoxic and Hypoxic Mesenchymal Stem Cells in Regulating Platelet-derived Growth Factors and Collagen Serial Levels in Skin Excision Animal Models

BACKGROUND: The healing process of a skin excisions involves a complex cascade of cellular responses to reverse skin integrity formation. These processes require growth factors particularly platelet-derived growth factors (PDGF). On the other hand, hypoxia- preconditioned mesenchymal stem cells (MSCs) could secrete growth factors that notably contribute to wound healing acceleration, characterized by the enhancement of collagen density. AIM: This study was aimed to investigate the role of hypoxia-preconditioned MSCs in regulating the serial levels of PDGF associated with the enhancement of collagen density in the skin excision animal models. METHODS: Twenty-seven male Wistar rats of skin excision were created as animal models. The animals were randomly assigned into four groups consisting of two treatment groups (treated by normoxia-preconditioned MSCs as T1 and hypoxia-preconditioned MSCs as T2), positive control (treated with phosphate-buffered saline) and sham (non-treated and healthy rats). PDGF levels were examined by ELISA. The collagen density was determined using Masson‘s trichrome staining. RESULTS: This study showed that there was a significant increase in PDGF levels on days 3 and 6 after hypoxia- preconditioned MSCs treatment. In line with these findings, the collagen density was also increased significantly after hypoxia-preconditioned MSCs treatment on days 3, 6, and 9. CONCLUSION: Hypoxia-preconditioned MSCs could regulate the serial PDGF levels that lead to the enhancement of collagen density in the skin excision rat’s model.

Sitagliptin ameliorates diabetic nephropathy by upregulating renal nephrin and podocin expression through modulation of adipokines levels.

Diabetic nephropathy is the leading cause of end-stage renal failure, but the effectiveness of currently available strategies for preventing diabetic nephropathy remains unsatisfactory. This study was designed to evaluate the changes in adipokines levels caused by dipeptidyl peptidase-4 inhibitor sitagliptin therapy as one of the possible mechanisms of sitagliptin's amelioration of diabetic nephropathy. Twenty-four male Wistar rats weighing 180-200 g were taken and divided into three groups, that is, control, diseased, and treatment group. High-fat diet and streptozotocin-induced Type 2 diabetic rats were divided into diseased and treatment groups. The treatment group was given sitagliptin orally, 10mg/kg per day for 6weeks. Serum glucose, serum insulin, serum blood urea nitrogen, serum creatinine, and 24-h urinary protein levels were measured in serum and urine samples. mRNA expression levels of podocin, nephrin, and adipokines in renal tissues were determined. Results showed that sitagliptin treatment effectively reduced serum glucose, serum creatinine, serum blood urea nitrogen, and 24-h proteinuria, along with partial prevention of insulinopenia, in the treatment group as compared to the diseased group. The renal mRNA expression levels of podocin, nephrin, and adiponectin were significantly upregulated, while those of leptin and resistin were significantly downregulated in the diabetic rats receiving sitagliptin therapy compared to the non-treated diabetic rats. Based on these findings, it is suggested that sitagliptin, via mediating the modulation of adipokines levels, upregulates renal nephrin and podocin expression, which leads to the amelioration of diabetic nephropathy.

Prevention by the CXCR2 antagonist SCH527123 of the calcification of porcine heart valve cusps implanted subcutaneously in rats.

Calcification is a main cause of bioprosthetic heart valves failure. It may be promoted by the inflammation developed in the glutaraldehyde (GA)-fixed cusps of the bioprosthesis. We tested the hypothesis that antagonizing the C-X-C chemokines receptor 2 (CXCR2) may prevent the calcification of GA-fixed porcine aortic valves. Four-week-old Sprague Dawley males were transplanted with 2 aortic valve cusps isolated from independent pigs and implanted into the dorsal wall. Four groups of 6 rats were compared: rats transplanted with GA-free or GA-fixed cusps and rats transplanted with GA-fixed cusps and treated with 1 mg/kg/day SCH5217123 (a CXCR2 antagonist) intraperitoneally (IP) or subcutaneously (SC) around the xenograft, for 14 days. Then, rats underwent blood count before xenografts have been explanted for histology and biochemistry analyses. A strong calcification of the xenografts was induced by GA pre-incubation. However, we observed a significant decrease in this effect in rats treated with SCH527123 IP or SC. Implantation of GA-fixed cusps was associated with a significant increase in the white blood cell count, an effect that was significantly prevented by SCH527123. In addition, the expression of the CD3, CD68 and CXCR2 markers was reduced in the GA-fixed cusps explanted from rats treated with SCH527123 as compared to those explanted from non-treated rats. The calcification of GA-fixed porcine aortic valve cusps implanted subcutaneously in rats was significantly prevented by antagonizing CXCR2 with SCH527123. This effect may partly result from an inhibition of the GA-induced infiltration of T-cells and macrophages into the xenograft.

Oral administration of baicalein-enriched fraction during pre- and post-ischemic stroke alleviated cognitive impairments in rat models

<abstract> <p>In recent years, numerous studies have discovered the potential of natural compounds extracted from medicinal plants as a promising alternative treatment for ischemic stroke (IS). <italic>Oroxylum indicum</italic> is among the plants that has been widely proven to contain a beneficial flavonoid compound known as baicalein. However, the therapeutic potential of this compound for IS disease has yet to be demonstrated. In this study, a baicalein-enriched fraction (BEF) was harvested from the leaves of <italic>O. indicum</italic> and tested on neural stem cells (NSCs) to determine its effects on the cell viability and gene expression prior to an in vivo animal study. NSCs were chosen because they are the primitive brain cells that play important roles in neurogenesis after IS injury. It was found that NSCs treated with BEF at concentration of 3.125 µg/mL for 48 hours showed a significant higher cell proliferation rate. Moreover, these cells expressed high NSC markers (Nestin and SOX2) and genes responsible for antioxidant (SOD2) and angiogenesis (ANGPT1) mechanisms, indicating that the BEF treatment could enhance the progenitor brain cells viability and the expression of cytokines that are beneficial to reduce oxidative stress and reinstate blood flow in an ischemic brain. Subsequently, the in vivo therapeutic effects of BEF for IS disease was tested by administering 50 mg/kg b.wt of BEF to male Sprague Dawley (SD) rats via oral gavage before and after induction of IS. Assessments of neurological impairments were performed using a modified neurological severity score (mNSS) and the quantification of the total infarct volume was evaluated as the endpoint of this study. Results showed that an oral administration of BEF improved the behavioral scoring for motor functions (forelimb flexion and forelimb twisting), contralateral sensory functions (paw-whiskers test), motor coordination, balance functions (beam balance test) and reflex functions (pinna, corneal, startle and tail reflex) within 24–72 h; alternatively, the non-treated rats showed continuously lower scores for all the tests throughout the study, indicating that the BEF-treated rats exhibited a faster recovery rate as compared to the non-treated rats. Such improvements were observed up to two weeks. In addition, histological assessment also revealed a reduction of infarct volume in the BEF-treated rats as compared to the control rats. In summary, the present study demonstrated the potential of BEF extracted from the <italic>O. indicum</italic> as a supplement to improve preclinical IS models.</p> </abstract>

Hyperbaric oxygen exposure alleviate metabolic side-effects of olanzapine treatment and is associated with Langerhans islet proliferation in rats.

Introduction: Olanzapine (OLZ) is one of the second-generation antipsychotics drugs (APDs) used to treat several psychiatric illnesses. Olanzapine treatment is often associated with many metabolic side effects in a dose dependent manner such as obesity, dyslipidemia and insulin resistance, induction of type II diabetes and acute pancreatitis in some patients. Methods: Hyperbaric Oxygen therapy (HBOT) was investigated as a tool to mitigate olanzapine metabolic side effects in rats. Thirty-six female Sprague Dawley (SD) rats were divided into 4 groups; rats on olanzapine treatment either exposed to hyperbaric oxygen therapy (HBOOLZ) or left without exposure (OLZ) then non-treated rats that either exposed to hyperbaric oxygen therapy or left without exposure (control). Rats received Hyperbaric Oxygen therapy for 35 days at 2.4 atmospheres absolute (ATA) for 2.5 h daily followed by intraperitoneal injection of olanzapine at 10 mg/kg or placebo. Results: Rats on either hyperbaric oxygen therapy or olanzapine had a significant loss in body weight. Olanzapine treatment showed a decrease in serum insulin level, triglyceride, highdensity lipoprotein (HDL) cholesterol, and lipase level but an increase in fasting blood sugar (FBS), insulin resistance index (HOMA-IR) and amylase, while rats' exposure to hyperbaric oxygen therapy reversed these effects. The Pancreatic Langerhans islets were up-regulated in both hyperbaric oxygen therapy and olanzapine treatments but the combination (HBOOLZ) doubled these islets number. Discussion: This study advocated that hyperbaric oxygen therapy can be an alternative approach to control or reverse many metabolic disorders (MDs) associatedwith olanzapine treatment. In addition, it seems that hyperbaric oxygen therapy positively affect the pancreatic Langerhans cells activity and architecture.

Effects of growth hormone on lipid metabolism and sexual development in pubertal obese male rats.

To investigate the effects of growth hormone (GH) on pubertal obese male rats, a rat model of high-fat diet-induced obesity was established in juvenile male rats. The model rats were divided into the treatment group (GH) and the non-treatment group (physiological saline). After 4 weeks, we measured the levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), estrogen (E2), testosterone (T), and insulin-like growth factor (IGF-1). The morphological changes of the liver and testis were assessed, and the expression of aromatase was detected. The levels of ALT, AST, TC, TG, LDL-C, E2, and IGF-1 in the treatment group were significantly lower than in the non-treated model rats (P < 0.001). The levels of HDL-C and T of GH-treated rats were significantly higher than those of the non-treatment group (P < 0.001). Compared with non-treated model rats, GH-treated model rats showed reduced liver steatosis, improved morphological structure of the testicular seminiferous tubules, and an increased number of spermatogenic cells. The treatment group also showed lower expression of aromatase in the liver and testis compared with the non-treatment group. GH partially protected pubertal male rats from obesity-induced lipid metabolic disorder and sexual retardation.

Improvement of Behavioural Scoring and Infarct Volume Sizes in Ischemic Stroke Rats Treated with Baicalein

&#x0D; Stroke is a cerebrovascular disease, contributing to major morbidity and mortality worldwide, with significant clinical and socioeconomic burdens [1]. In Malaysia, stroke is ranked as the third leading cause of death after ischemic heart disease and pneumonia with an alarming rising trend [2]. There are two major types of strokes, namely ischemic stroke (IS) and haemorrhagic stroke. IS caused by thromboembolic occlusion of cerebral artery is the main type of stroke in Malaysia, in which it is comprised up to two-third of total reported stroke cases, as compared to the haemorrhagic stroke [3]. Main pathological events of brain ischemia include a series of biological reactions such as oxidative stress, inflammatory cytokine release, and ischemic-reperfusion injury, leading to cell apoptosis and irreversible neurological damage [4]. Up to date, recombinant tissue plasminogen activator (rt-PA) is still the gold standard drug approved by Food and Drug Administration (FDA) for the clinical treatment of IS [5]. However, due to its narrow therapeutic window (&lt;4.5h), high re-incidence rate and short half-life (&lt;5 min) [5], the application of rt-PA is limited [6]. Therefore, many researchers are exploring other therapeutic approaches to tackle this disease. &#x0D; &#x0D; In recent years, increasing evidences have discovered the potential of natural compounds extracted from plants as a promising alternative strategy against IS. Among the potential plant that possess blood-brain barrier properties, an important characteristics as neuroprotective agent for neurological disorder is Oroxylum indicum [6]. It has been reported that O. indicum has a dominant active compound, namely as baicalein that are responsible in this plant’s biological activities [7]. Therefore, in this study, we aimed to evaluate the potential of baicalein extracted from the leaves of Oroxylum indicum to treat the diseases. Briefly, 10 male Sprague Dawley rats were used in this study (n=5). 50 mg/kg b.wt of baicalein was orally administered via oral gavage before and after induction of ischemic stroke by endothelin-1 (ET-1), while control group was given normal saline. Assessments of behavioral scoring using modified neurological severity score (mNSS) and infarct volume by 2,3,5-triphenyltetrazolium chloride (TTC) staining were evaluated as the endpoint of this study.&#x0D; &#x0D; Results demonstrated that the oral administration of baicalein improved the behavioral scoring of rats in motor test (forelimb flexion and forelimb twisting), contralateral sensory test (paw-whiskers), motor coordination and balance function and reflex test (pinna, corneal, startle and tail reflex) within 24 h -72 h, indicating that the baicalein-treated rats exhibited faster recovery rate as compared to non-treated rats (Figure 1A-D). Such improvements were observed up to two weeks. In addition, histological assessment using TTC staining also revealed reduction of infarct volume in baicalein-treated rats as compared to control rats. However, the percentage of infarct volume to whole brain was not significantly different in both groups (Figure 2).&#x0D; The promising results displayed by baicalein might be contributed by its anti-inflammatory property. Several studies reported that baicalein, a type of flavonoid compound, are responsible in attenuation of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage and inhibit NF-kB activation [7,8]. LPS is the potent macrophage activator, while NF-kB is a transcription factor that can cause inflammatory cytokines release in various cell types [9, 10]. In summary, the present study demonstrates that oral administration of baicalein in ischemic stroke rats could be effectively addressed and improved behavioral scoring in treated rats as early as 24 h after baicalein treatment. &#x0D;

Rho-kinase inhibition ameliorates non-alcoholic fatty liver disease in type 2 diabetic rats.

Non-alcoholic fatty liver disease (NAFLD) is linked to type 2 diabetes mellitus (T2DM), obesity, and insulin resistance. The Rho/ROCK pathway had been involved in the pathophysiology of diabetic complications. This study was designed to assess the possible protective impacts of the Rho/Rho-associated coiled-coil containing protein kinase (Rho/ROCK) inhibitor fasudil against NAFLD in T2DM rats trying to elucidate the underlying mechanisms. Animals were assigned into control rats, non-treated diabetic rats with NAFLD, and diabetic rats with NAFLD that received fasudil treatment (10 mg/kg per day) for 6 weeks. The anthropometric measures and biochemical analyses were performed to assess metabolic and liver function changes. The inflammatory and oxidative stress markers and the histopathology of rat liver tissues were also investigated. Groups with T2DM showed increased body weight, serum glucose, and insulin resistance. They exhibited disturbed lipid profile, enhancement of inflammatory cytokines, and deterioration of liver function. Fasudil administration reduced body weight, insulin resistance, and raised liver enzymes. It improved the disturbed lipid profile and attenuated liver inflammation. Moreover, it slowed down the progression of high fat diet (HFD)-induced liver injury and reduced the caspase-3 expression. The present study demonstrated beneficial amelioration effect of fasudil on NAFLD in T2DM. The mechanisms underlying these impacts are improving dyslipidemia, attenuating oxidative stress, downregulated inflammation, improving mitochondrial architecture, and inhibiting apoptosis.

The Effects of Hydroalcoholic Extract of Silk Cocoon on Hypothalamic-Pituitary -Gonadal Axis in Streptozotocin-Induced Diabetic Male Rats.

Background Diabetes mellitus impairs the reproductive system by damaging the glands and changing their function and hormone secretions. Given the previous studies on medical properties of silk cocoon, the aim of this study was to investigate the effect of the hydroalcoholic extract of silk cocoon on pituitary-gonadal axis hormones and the testis changes in diabetic male rats. Methods In this experimental study, 35 male rats were divided into 5 equal groups. Control (C), nontreated diabetic rats (DNT1), and experimental diabetic rats treated (DT1) with a silk cocoon extract at concentrations of 200, 400, and 800 mg/kg for 56 days. Diabetes was induced by an injection of streptozotocin. Blood sampling was performed by the tail and heart after fasting. Body weight, serum levels of glucose, prolactin, leptin, inhibin A, IGF-2, activin A, insulin, LH, testosterone, FSH, and GnRH were measured along with the testis weight and diameter as the outcome of the study. Data were analyzed by SPSS version 20. Results Investigation of hormonal factors indicated that all diabetic groups had higher prolactin, inhibin A levels than those in C group and lower leptin, IGF-2, activin A, insulin, LH, testosterone, FSH, and GnRH levels than controls. Silk cocoon treatment significantly decreased prolactin and inhibin in comparison of DNT1 group. While there was a significant increase in leptin, IGF-2, activin A, insulin, LH, testosterone, FSH, and GnRH levels compared with DNT1 (P < 0.05). A significant decrease in both the testis weights and diameters was observed in diabetic male rats compared to controls (P < 0.05). While silk cocoon treatment improved gonadal weight, the diameter of tunica albuginea, and seminiferous tubules as long as increased in numbers of spermatocytes and Sertoli-Leydig cells. Spermatogonia, spermatocyte, spermatid, spermatozoid, Sertoli cells, and Leydig cell count were significantly lower in the DNT1 group in comparison with the control group, while all groups receiving the highest dose of SC800 mg/kg daily had a higher count of cells than the DNT1 group. Conclusion It seems that silk cocoon treatment decreases the effects of diabetes on hypothalamic-pituitary–gonadal axis.

Ameliorative effect of Lactobacillus rhamnosus GG on acetaminophen-induced hepatotoxicity via PKC/Nrf2/PGC-1α pathway

BackgroundAcetaminophen (APAP) overdose is a common cause of hepatotoxicity. Antioxidants like N-acetyl cysteine are recommended as a therapeutic option; nevertheless, it has limitations. The search for efficient alternatives is ongoing. Probiotics are live microorganisms that maintain a healthy gut microecology. Lactobacillus rhamnosus GG (LGG) is one of the widely used probiotics. Our study aimed to assess the protective and therapeutic effects of probiotic LGG on APAP-induced hepatotoxicity and evaluate the molecular pathways behind this effect. MethodsWistar Albino male rats were randomly distributed into the following experimental groups: group 1, non-treated rats (vehicle); group 2, rats received oral gavage of suspension of probiotic LGG (5 × 1010 CFU GG/0.5 ml in PBS) daily for 2 weeks (probiotic control); group 3, rats received APAP dose of 2 g/kg body weight (positive control); group 4, rats received oral gavage of suspension of probiotic LGG for 2 weeks followed by a single dose of APAP injection (prophylactic); and group 5, rats received a single dose of APAP and then 24 h later treated with oral gavage of probiotic LGG daily for 2 weeks (treatment). ResultsOur study revealed that administration of probiotic LGG (either as prophylactic or treatment) exhibited a remarkable reduction in APAP-induced liver injury as resembled by the decrease in liver enzymes (ALT and AST) and the histopathological features of liver sections. Moreover, the significant reduction in the oxidative marker malondialdehyde, along with the enhancement in glutathione reductase, and the significant reduction in inflammatory markers (nitric oxide and tumor necrosis factor-α) were all indicators of the efficiency of LGG in ameliorating the alterations accompanied with APAP-induced hepatotoxicity. Our findings also demonstrate that LGG administration boosted the expression of Nrf2 and PGC-1 while decreasing the expression of protein kinase C (PKC). As a result, the nuclear abundance of Nrf2 is increased, and the expression of various antioxidants is eventually upregulated. ConclusionOur study shows that probiotic LGG supplementation exerts a prophylactic and therapeutic effect against APAP-induced hepatotoxicity through modulating the expression of PKC and the Nrf2/PGC-1α signaling pathway and eventually suppressing oxidative damage from APAP overdose.

Effect of Folic Acid Conjugated Silver Nanoparticles in Treatment of RA Like Adjuvant Arthritis in Rats

Objective: Nano medicine has become one of the promising research areas, opening new horizons in disease diagnosis and treatment. Recent years have witnessed a surge in the development of Nano medicine for combating rheumatoid arthritis (RA), the most common autoimmune arthritis. RA is characterized by progressive inflammation and persistent synovitis, leading to joint destruction, functional incapability, and ultimately disability. Although there has been a tremendous evolution in disease assessment and treatment, many patients still fail to attain remission. Therefore, developing new drugs that specifically target inflamed joints and simultaneously attenuate other possible damages to healthy tissues is indispensable. This study was done to evaluate the potential of folic acid conjugated silver nanoparticles (FA-AgNPs) as RA therapy. Methods: In the CFA-arthritic rat model, FA-AgNPs &amp; methotrexate were administered for 8 consecutive weeks. Therapeutic efficacy was evaluated by measuring paw volume, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) levels. For safety concerns, complete blood picture (CBC), liver and renal function tests were evaluated. Joints histological assessment was also carried out. Results: FA-AgNPs significantly reduced paw volume, paw weight, ESR, CRP, RF, TNF-α, and IL-6 levels compared with arthritic non-treated rats, demonstrating good anti-inflammatory activity. Likewise, histology of tarsal joints depicted comparatively lesser inflammatory cellular infiltration and diminished cartilage erosions. Methotrexate displayed comparable results. In contrast to methotrexate, FA-AgNPs showed normal CBC &amp; significantly improved liver and renal function tests. Conclusion: FA-AgNPs exhibited substantial anti-arthritic activity. This notable anti-arthritic potential of FA-AgNPs was as good as the current standard treatment of methotrexate (MTX) with higher biosafety.

Brassica oleracea L. var. botrytis Leaf Extract Alleviates Gentamicin-Induced Hepatorenal Injury in Rats-Possible Modulation of IL-1β and NF-κB Activity Assisted with Computational Approach.

Background: Recently, crop byproducts are considered a hot topic and can be converted into beneficial products. Cauliflower is well-known for its protective effects against oxidative stress-induced damage. The current study aimed to investigate the chemical profile and the ameliorative effects of cauliflower leaf extract (CL) on gentamicin-induced renal and hepatic injuries in rats. Methods: Cauliflower leaf was extracted with methanol to give the total methanol extract (TME) followed by the determination of total phenolic contents (TPC). Rats were divided into five groups; Group I was assigned as the control group, while the other groups were injected with gentamicin for ten days. Group II was given distilled water. Rats in groups III and IV were treated with oral CL (200 mg/kg and 400 mg/kg, respectively). Group V received L-cysteine (as a positive control). The functions of the kidneys and liver; oxidative stress and morphological and apoptotic changes of renal and hepatic tissues were assessed. Results: The TME was subjected to chromatographic techniques to yield ferulic acid, vanillic acid, p-coumaric acid and quercetin. TPC was 72.31 mg GAE/g of dried extract. CL treatment dose-dependently ameliorated gentamicin-induced impaired kidney and liver functions and improved the histopathological appearance of both organs. It also reduced gentamicin-induced oxidative stress. CL demonstrated downregulation of mRNA and protein expressions of IL-1β and NF-κB compared to nontreated rats. In silico interaction of the isolated compounds with amino acid residues of IL-1β and NF-κB might explain the current findings. Conclusion: Taken together, this study raises the waste-to-wealth potential of cauliflower to mitigate gentamicin-induced hepatorenal injury and convert the waste agromaterials into valuable products.

Potential therapeutic effect of platelet-rich plasma and albendazole on the muscular phase of experimental Trichinella spiralis infection

Trichinellosis is a food-borne parasitic infection causing muscle damage. This study aimed to detect the potential therapeutic effect of platelet-rich plasma (PRP) alone or in combination with albendazole (ALB) on the muscular phase of experimental Trichinella infection in rats. The study was conducted on 70 rats divided into four main groups: healthy non-infected non-treated rats, non-infected rats treated with PRP, infected untreated rats (seven rats in each group), and an infected group of 49 rats. The infected group was further subdivided based on the drug therapy received. The effects of drug therapy were evaluated using parasitological and histopathological analyses.The percent reduction in the number of Trichinella spiralis larvae per gram of muscle in the PRP-treated groups (one, two, and three doses) was 43.1%, 78.8%, and 86.1%, respectively. Groups treated with combined therapy of ALB & PRP (one, two, and three doses) showed overall reduction percentages of 87.7%, 90.9% and 95.2%, respectively. In contrast, the ALB-treated group showed a 69.4% reduction. All results of the abovementioned groups were statistically significant compared to the control-infected non-treated group.The findings of the histopathological analysis were consistent with the parasitological results. Groups receiving combined therapy showed the most significant improvement in terms of the degree of inflammation and fibrosis. It can be concluded that PRP has a modulatory effect on the pathology caused by T. spiralis larvae in the muscular phase of trichinellosis.To our knowledge, this is the first study to investigate the effect of PRP on the muscular phase of T. spiralis infection.

Tridax procumbens Ameliorates Streptozotocin-Induced Diabetic Neuropathy in Rats via Modulating Angiogenic, Inflammatory, and Oxidative Pathways.

Tridax procumbens (TP) is a traditional Indian therapeutic plant and was evaluated for its blood glucose lowering abilities, as well as for its ability to curb diabetic neuropathy (DN). Administrating 45 mg/kg body weight of streptozotocin (STZ) intraperitoneally for four weeks, DN was induced in Wistar rats. After the rats' tails were clipped, the blood glucose levels were measured. Body weight and urine volume were also assessed. Oxidative stress makers such as superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS), catalase (CAT), inflammatory cytokines for instance tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were estimated. Further, protein kinase C (PKC-β) and vascular endothelial growth factor (VEGF) were also estimated as angiogenic markers. Behavioral parameters were also evaluated by using cold allodynia using acetone test, hot allodynia using Eddy's hot plate, grip strength test using Rota rod, and hyperalgesia test using Tail flick technique. The statistical assessment of findings was done employing one-way (ANOVA) analysis of variance, and subsequently Turkey as post hoc with GraphPad Prism software package. The ingestion of TP for 1 month in DN rats stemmed in a substantial decline in blood glucose concentrations matched to nontreated rats with DN. There had been a considerable improvement in DN as evident from the finding from biochemical markers. The serum level of antioxidant defense enzymes was significantly increased, while the activities of TBARS had been substantially reduced in the TP treated rats with DN. TP averted DN-triggered surge levels of TNF-α and IL-6 in the serum. Further, PKC-β and VEGF concentrations had been also reduced by the treatment TP. The findings of this research demonstrated that the restorative impact of TP on DN rats might be linked to the anti-inflammatory and antioxidative antiangiogenic retorts.

Investigation of TNFα Level and Metallothionein Gene Expression in Livers of Rats Exposed to Dietary Aluminum.

Aluminum chloride is a chemical compound widely used in both pharmaceutical and industrial sectors. The present study aimed to assess the effect of aluminum chloride on TNF levels and metallothionein gene expression in rat livers. A total of 16 Wistar rats were used as an experimental model and assigned to four groups (n=4). The treated groups received aluminum chloride (Sigma/USA) at a dose of 25g/kg body weight via a feeding tube as follows: group 1: Non-treated rats as the control group, group 2 were treated with aluminum chloride for 8 weeks, group 3 were treated with aluminum chloride for 12 weeks, and group 4 received aluminum chloride for 16 weeks. The TNF-α was measured in liver tissue using an enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry and real-time polymerase chain reaction(RT-PCR)were used to analyze metallothionein gene expression in rat liver. To estimate TNF levels, the results revealed that levels were considerably higher (P<0.01) in all experimental groups, especially in group 4 which underwent treatment for 16 weeks (401±22.1 ng/ml), as compared to that in the control group. For the immunohistochemistry assay, a gradient intensity of staining for liver tissue was observed, ranging from zero staining in the control group to moderate, medium, and high staining in the experimental groups after 8, 12, and 16 weeks of aluminum chloride treatment, respectively. The greatest amount of methylothionine expression was observed in the livers of group 4 which received aluminum chloride for 16 weeks (15.5-fold), with a significant difference (P<0.01) from the other experimental groups. In both immunohistochemical and RT-PCR experiments, aluminum administration had a substantial influence on TNFα levels and metallothionein expression in rat livers.

Combined Therapy of Chitosan and Exercise Improves the Lipid Profile, Adipose Tissue and Hepatic Alterations in an In Vivo Model of Induced-Hyperlipidemia

Obesity is a prevalent public health concern in several countries, and is closely associated with several pathological disorders, including diabetes, hypertension, cardiovascular diseases, and increased dyslipidemia. Dyslipidemia is an asymptomatic condition characterized by high levels of low-density lipoproteins (LDL) and low levels of high-density lipoproteins (HDL), leading to the increased risk of ischemic heart disease. As lipid disorders are strongly associated with lifestyle and diet, in this work we have evaluated the effect of associating chitosan and exercise on the improvement of the lipid profile of high-fat diet-fed rats. Animals were submitted orally to hypercaloric diets based on liquid butter at 1 mL/100 g to induce a hyperlipidemic state for 8 weeks (as shown by body weight and measures of the Lee obesity index). After 8 weeks, the 40 rats were separated into five groups (n = 8) and adapted to different treatment strategies: physical exercise and/or treatment with chitosan (at a concentration of 2%). The hyperlipidemic group exhibited altered levels of glucose and hepatic enzymes, i.e., aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The treatment with chitosan over 8 weeks significantly reduced the bodyweight of the animals, reaching values lower than the control group. Exercise reduced the Lee obesity index values of all the treated groups compared to non-treated rats. The concentration of total cholesterol, triglycerides, LDL, and VLDL was significantly reduced at the end of the study to healthy thresholds. The hepatic parenchyma of hyperlipidemic animals was recovered to show normal morphology when treated with chitosan; improved histological features (ca. 20–30% of parenchymal cells) could be achieved with physical exercise. In conclusion, oral administration of chitosan associated with physical exercise had a hypolipidemic effect in a model of dyslipidemia in rodents, showing decreased levels of total cholesterol, triglycerides, LDL-c, VLDL-c, glucose, and liver enzymes (AST and ALT). Our results are attributed to the synergism between the administration of chitosan and physical exercise that helps to reduce oxidative stress.

Effects of Fermented Camel Milk Supplemented with Sidr Fruit (Ziziphus spina-christi L.) Pulp on Hyperglycemia in Streptozotocin-Induced Diabetic Rats

Diabetes is one of the most common chronic metabolic diseases, and its occurrence rate has increased in recent decades. Sidr (Ziziphus spina-christi L.) is a traditional herbaceous medicinal plant. In addition to its good flavor, sidr has antidiabetic, anti-inflammatory, sedative, analgesic, and hypoglycemic activities. Camel milk has a high nutritional and health value, but its salty taste remains the main drawback in relation to its organoleptic properties. The production of flavored or fortified camel milk products to mask the salty taste can be very beneficial. This study aimed to investigate the effects of sidr fruit pulp (SFP) on the functional and nutritional properties of fermented camel milk. SFP was added to camel milk at rates of 5%, 10%, and 15%, followed by the selection of the best-fermented product in terms of functional and nutritional properties (camel milk supplemented with 15% SFP), and an evaluation of its hypoglycemic activity in streptozotocin (STZ)-induced diabetic rats. Thirty-two male adult albino rats (weighing 150–185 g) were divided into four groups: Group 1, nontreated nondiabetic rats (negative control); Group 2, diabetic rats given STZ (60 mg/kg body weight; positive control); Group 3, diabetic rats fed a basal diet with fermented camel milk (10 g/day); and Group 4, diabetic rats fed a basal diet with fermented camel milk supplemented with 15% SFP (10 g/day). The results revealed that supplementation of camel milk with SFP increased its total solids, protein, ash, fiber, viscosity, phenolic content, and antioxidant activity, which was proportional to the supplementation ratio. Fermented camel milk supplemented with 15% SFP had the highest scores for sensory properties compared to other treatments. Fermented camel milk supplemented with 15% SFP showed significantly decreased (p &lt; 0.05) blood glucose, malondialdehyde, low-density lipoprotein-cholesterol, cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, creatinine, and urea, and a significantly increased (p &lt; 0.05) high-density lipoprotein-cholesterol, total protein content, and albumin compared to diabetic rats. The administration of fermented camel milk supplemented with 15% SFP in diabetic rats restored a series of histopathological changes alonsgside an improvement in various enzyme and liver function tests compared to the untreated group, indicating that fermented camel milk supplemented with 15% SFP might play a preventive role in such patients.

Long-term If current blockade increases right atrial mRNA expression of HCN4, encoding proteins for If

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by a grant of the Romanian Ministry of Education and Research, CNCS - UEFISCDI, within PNCDI III Background Numerous long-term pharmacologic manipulations of cardiac ion channels have shown potential to modify the expression of genes encoding proteins for those channels. Purpose We aimed to investigate whether long-term pharmacologic inhibition of the hyperpolarization-activated inward current (If) using ivabradine affects the right atrial expression of genes encoding for hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, responsible for If. Methods The right atrial mRNA expression of HCN1, HCN2, and HCN4, and of the neuron-specific HCN3 isoform was quantified in 6 control (Control) and 12 ivabradine-treated (IVA; 10 mg/kg, 4 weeks) adult male Wistar rats. The expression levels of the target genes were normalized with GAPDH housekeeping gene levels and compared between the two groups. Results Right atrial HCN1 and HCN2 expression levels were both similar (both p &amp;gt;0.05) between the IVA and the Control rats. There was also no significant difference in the right atrial expression of the neuron-specific HCN3 isoform between the two groups (p = 0.22). However, the right atrial expression of HCN4, the most highly expressed HCN isoform in the sinus node, was significantly higher in the ivabradine-treated compared to the non-treated rats (p = 0.02). Conclusions Our study shows that chronic If blockade using ivabradine significantly up-regulates right atrial HCN4 expression. Although the examined samples contained both nodal and non-nodal tissue, since HCN4 is highly expressed in the nodal pacemaker cells and only sparsely in the remaining atrial myocardium, it is likely that the HCN4 changes observed in our study reflect sinus node alterations. HCN4 and a consequent If up-regulation could render the sinus node less sensitive to acute vagal inputs and protect against excessive vagal-induced bradycardia. Further studies will have to evaluate this hypothesis.