Single Intraperitoneal Injection Research Articles

Docosahexaenoic acid eliminates endoplasmic reticulum stress and inflammatory pathways in diabetic rat keratopathy

Diabetic keratopathy, characterized by corneal structural changes, is a common complication of diabetes mellitus (DM). Docosahexaenoic acid (DHA), an omega-3 fatty acid, has shown potential therapeutic benefits in various diabetic complications. This study aimed to investigate the protective effect of DHA on corneal tissue in streptozotocin (STZ)-induced type 2 DM in rats. Forty male Sprague–Dawley rats were randomly assigned to four groups (n = 10 per group): Control, DHA, DM, and DM + DHA. The DHA group received DHA by oral gavage at a dose of 100 mg/kg daily for 10 days. In the DM group, diabetes was induced by a single intraperitoneal injection of STZ at 50 mg/kg. Confirmation of diabetes induction was based on monitoring fasting blood glucose levels on the third day post-injection. The DM + DHA group underwent the same diabetes induction protocol with STZ and received DHA at 100 mg/kg daily via oral gavage for 10 consecutive days. Corneal tissue samples were collected at the end of the study period for histopathological, immunohistochemical, qRT-PCR, and ELISA analyses. Histopathological analysis showed significant edema, angiogenesis, and degeneration in the DM group compared to the control (p < 0.001). DHA treatment significantly mitigated these changes, approaching control levels (p < 0.01). Immunohistochemistry showed increased VEGFR2 and iNOS expression in the DM group, which was significantly reduced in the DM + DHA group (p < 0.01). qRT-PCR results indicated a significant decrease in Bcl-2 expression (p < 0.001) and an increase in ATF-6, IRE1, NF-κB, TNF-α, IL-1β, NLRP3, Bax, and Caspase-3 expressions in the DM group (p < 0.001). ELISA analyses revealed significantly elevated levels of inflammatory markers NF-κB, TNF-α, IL-1β, and IL-6 in the DM group compared to the control (p < 0.001). DHA treatment significantly upregulated Bcl-2 and downregulated apoptotic and inflammatory markers (p < 0.01). DHA demonstrated significant protective effects against STZ-induced corneal damage in diabetic rats by modulating apoptotic and inflammatory pathways. These findings suggest that DHA may be a promising therapeutic agent for preventing diabetic keratopathy.

The potential protective effect of propolis on diabetic nephropathy induced by streptozotocin in adult albino rats

ABSTRACT Diabetes mellitus is a common metabolic disorder. It is associated with serious life-threatening complications if not properly managed. The current study aimed at investigating the possible protective role of propolis on streptozotocin-induced diabetic nephropathy. A diabetic rat model was induced by a single intraperitoneal injection of 55 mg/kg streptozotocin. After 4 days, the diabetic rats received oral propolis (300 mg/kg/day) via gastric gavage for 28 days. Biochemical, histopathological and ultrastructural evaluations were performed. The results showed that: streptozotocin-induced diabetes was associated with a marked decrease in the serum high-density lipoproteins and antioxidant enzymes. However, a significant elevation in the levels of serum creatinine, blood urea nitrogen, uric acid, cholesterol, triglycerides and low-density lipoproteins was detected. Furthermore, streptozotocin treatment induced histopathological alterations of the renal cortex; in the form of distorted glomerular capillaries, widened Bowman’s space and signs of epithelial tubular degeneration. Ultra-structurally, thickening and irregularity of the glomerular basement membrane and podocytes foot processes effacement were observed. The tubular epithelial cells showed swollen vacuolated mitochondria, scarce basal infoldings and loss of microvilli. Conversely, propolis partially restored the normal lipid profile, antioxidant biomarkers and renal cortical morphology. Propolis exhibited a sort of renoprotection through hypoglycemic, anti-hyperlipidemic and antioxidant effects.

Linagliptin mitigates cisplatin-induced kidney impairment via mitophagy regulation in rats, with emphasis on SIRT-3/PGC-1α, PINK-1 and Parkin-2

Cisplatin (CDDP) often leads to kidney impairment, limiting its effectiveness in cancer treatment. The lack of mitophagy in proximal tubules exacerbates this issue. Hence, targeting SIRT-3 and PGC1-α shows promise in mitigating CDDP-induced kidney damage. The potential renoprotective effects of linagliptin, however, remain poorly understood. This study represents the first exploration of linagliptin's impact on CDDP-induced kidney impairment in rats, emphasizing its potential role in mitophagic pathways. The experiment involved four rat groups: Group (I) received saline only, Group (II) received a single intraperitoneal injection of CDDP at 6 mg/kg. Groups (III) and (IV) received linagliptin at 6 and 10 mg/kg p.o., respectively, seven days before CDDP administration, continuing for an additional four days. Various parameters, including renal function tests, oxidative stress, TNF-α, IL-1β, IL-6, PGC-1α, FOXO-3a, p-ERK1, and the gene expression of SIRT-3 and P62 in renal tissue, were assessed. Linagliptin improved renal function, increased antioxidant enzyme activity, and decreased IL-1β, TNF-α, and IL-6 expression. Additionally, linagliptin significantly upregulated PGC-1α and PINK-1/Parkin-2 expression while downregulating P62 expression. Moreover, linagliptin activated FOXO-3a and SIRT-3, suggesting a potential enhancement of mitophagy. Linagliptin demonstrated a positive impact on various factors related to kidney health in the context of CDDP-induced impairment. These findings suggest a potential role for linagliptin in improving cancer treatment outcomes. Clinical trials are warranted to further investigate and validate its efficacy in a clinical setting.

Tannins-enriched fraction of TeMac™ protects against aluminum chloride induced Alzheimer's disease-like pathology by modulating aberrant insulin resistance and alleviating oxidative stress in diabetic rats

Ethnopharmacological relevanceAlzheimer's disease is the most common neurodegenerative disease with therapeutic limitations. Insulin resistance plays a role in the progression of Alzheimer's disease. Therapies that modulate insulin secretion and signaling, as well as oxidative stress in the brain are now being investigated for their potential role in the prevention of Alzheimer's disease (AD). Terminalia macroptera (Combretaceae) is a plant that different parts have been used traditionally for the treatment of metabolic and neurological conditions. Previous study has indicated that the crude extract exhibit anti-diabetic property. In addition, the plant is a rich source of tannins, phenolic acids, flavonoids, triterpenes. However, there is no study on its protective effect against biochemical alterations of AD in diabetic rats. Aim of the studyThe present research study investigated the neuroprotective effects of TeMac™ on Alzheimer-like pathology induced by aluminum chloride (AlCl3) in diabetic rats. MethodsA phytochemical analysis of TeMac™ was carried out to quantify tannins. The potential effect of the tannins-enriched fraction (TEF) of TeMac™ to prevent the formation of senile plaques was conducted by its ability to inhibit the activities of β-secretase (EC 3.4.23.46), monoamine oxidase A (EC 1.4.3.4) and the fibrillation of Aβ. A diabetic model was induced from female Wistar rats by a single intraperitoneal injection of streptozotocin (STZ, 35 mg/kg BW). After that, the blood glucose level was measured to confirm the induction of diabetes. Three days after induction, animals received AlCl3 (75 mg/kg BW) alone (AD control) or concomitantly with 400 mg/kg BW of TEF of TeMac™ or 5 mg/kg BW Daonil by daily gavage for 42 days. At the end of the experiment, rats were sacrificed, blood and brains were collected. The levels of amyloid fibrils, glucose, albumin and the activities of DPP4, β-secretase and phosphatase, and markers of oxidative stress in the brain were assessed. ResultsTEF of TeMac™ displays a potential ability to inhibit the activities of β-secretase, monoamine oxidase, and Aβ fibrillation. Treatment with TEF of TeMac™ significantly inhibited DPP4 and BACE1 activities and reduced brain glucose and amyloid fibril levels, and improved cerebral albumin levels and modulated oxidative stress markers. ConclusionOur findings indicate that TEF of TeMac™ prevents Alzheimer's-type pathology linked to insulin resistance in rats. TEF of TeMac™ may be a potential drug candidate for the treatment of diabetes-associated cognitive impairment.

Empagliflozin mitigates methotrexate-induced nephrotoxicity in male albino rats: insights on the crosstalk of AMPK/Nrf2 signaling pathway

BackgroundThe anti-diabetic drug, empagliflozin (EMPA), has many pleiotropic actions and is challenged recently to possess renoprotective properties. This renoprotective potential is proposed to be mediated via the activation of AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. This research investigated the renoprotective potential and the mechanistic pathway of EMPA against methotrexate (MTX)-induced nephrotoxicity and evaluated the role of AMPK by utilizing an AMPK inhibitor, dorsomorphin (Dorso).MethodsThirty male Wistar rats, weighing 180–200 g, were divided equally into five groups. Group I represented the control group. Nephrotoxicity was induced in the remaining rats through the administration of a single intraperitoneal injection of MTX (20 mg/kg). Rats were then randomly assigned to: Group 2 (received MTX injection only); Group 3 (received MTX and EMPA 30 mg/kg/day); Group 4 (received MTX and Dorso 0.2 mg/kg/day), Group 5 (received MTX, Dorso, EMPA). After one week, blood samples were collected, the rats were euthanized, and renal tissues were harvested for biochemical and histomorphometric assessments.ResultsMTX produced a significant rise in serum creatinine and tissue MDA levels; an increase in BAX, p53, cytochrome-c expression; a reduction in Bcl2 level; and disruption of renal microarchitecture. In contrast, EMPA therapy in group 3, resulted in a significant improvement of all these parameters, correlated with significant increase in AMPK phosphorylation and Nrf2 expression. Importantly, the co-administration of Dorso, in group 5, prevented EMPA’s beneficial effects.ConclusionEMPA has a potential protective effect against MTX-induced toxicity through the activation of the AMPK/Nrf2 signaling pathway.

Neuroprotective Effect of Clemastine Improved Oligodendrocyte Proliferation through the MAPK/ERK Pathway in a Neonatal Hypoxia Ischemia Rat Model

Neonatal hypoxic-ischemic encephalopathy is the most common cause of long-term disability in term neonates, and white matter injury is the primary cause of cerebral palsy. Therapies that focus on the neuroprotection of myelination and oligodendrocyte proliferation could potentially ameliorate long-lasting neurological impairments after hypoxic-ischemic encephalopathy. Clemastine, a histamine H1 antagonist, has been shown to exert neuroprotective effects in multiple sclerosis and spinal cord injury by promoting oligodendrogenesis and re-myelination. In this study, we demonstrated the neuroprotective effects of clemastine in our rat model of neonatal hypoxic-ischemic brain injury. Animals received a single intraperitoneal injection of either vehicle or clemastine (10 mg/kg) for 6 consecutive days. Our results showed a significant reduction in white matter loss after treatment, with a clear effect of clemastine on oligodendrocytes, showing a significant increase in the number of Olig2+ cells. We characterized the MAPK/ERK pathway as a potential mechanistic pathway underlying the neuroprotective effects of clemastine. Altogether, our results demonstrate that clemastine is a potential compound for the treatment of hypoxic-ischemic encephalopathy, with a clear neuroprotective effect on white matter injury by promoting oligodendrogenesis.

Comparative Evaluation of Diabetes Complication Using Liver Function Parameters as Indices between Male and Female Alloxan Induced Diabetic Rats

It is known that diabetes causes liver damage. On the other hand, because most cases of liver damage have been investigated in males, examining the relationship of this disease in both sexes is of great importance. This study was aimed at, comparatively evaluating diabetic complications using histopathological examination and liver function parameters as indices in alloxan-induced diabetic rats. A total of 24 male and female rats divided into four groups of six animals each were used for the experiment. Group A were female control, Group B were male control while group C and D were alloxan induced diabetic female and male rats respectively. Groups A and B were non diabetic rats fed with rat diet all through the experiment. Group C and D were diabetes induced with a single intraperitoneal injection of alloxan (120mg/kg). At the end of the inducement period, the rats were fasted overnight and sacrificed. Blood was collected by ocular puncture for the determination of fasting plasma glucose (FPG) and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TB), direct bilirubin (DB), total protein (TP) and albumin (ALB) using spectrophotometric method. Histology of the liver was determined by H and E technique. The results showed the experimental group C (365.83±43.6mg/dl) and D (368.94±43.93mg/dl) had significantly elevated levels of FPG when compared with the controls group A (116.00±9.11mg/dl) and B (108.33±5.5mg/dl) confirming the induction of diabetes (P=0.000). The liver of both male and female diabetic rats showed ballooning degeneration. In the males, these were arranged in normal sheets and cord around central vein in some areas of the center, on the other hand, the central vein of the female diabetic rats appears slightly enlarged containing blood clots and the arrangement of the hepatocytes in sheets or cords around the central vein was completely distorted. There was no significant difference (p&gt;0.05) in the mean serum levels of ALP, AST, ALT, DB, TP and ALB in female diabetics when compared to male diabetic rats. The mean serum level of TB was significantly reduced (p=0.004) in female diabetics (0.53±0.05) than in the male diabetic albino rats (0.69±0.09). This study showed the liver histology and function are variably altered in diabetes mellitus. Further research on the causes of liver damage will help us to unravel the pathogenesis of diabetes and its complications.

Comparative safety and efficacy of autogenous vaccine administrated by different routes against furunculosis caused by Aeromonas salmonicida sub. salmonicida in large Rainbow trout (Oncorhynchus mykiss)

The development and growth of fish farming are hindered by viral and bacterial infectious diseases, which necessitate effective disease control measures. Furunculosis, primarily caused by Aeromonas salmonicida, stands out as a significant bacterial disease affecting salmonid fish farms, particularly rainbow trout. Vaccination has emerged as a crucial tool in combating this disease. The objective of this experiment was to assess and compare the efficacy and duration of different vaccine protocols against furunculosis in large trout under controlled rearing conditions, utilizing single and booster administrations via intraperitoneal, oral, and immersion routes. Among the various vaccination protocols tested, only those involving intraperitoneal injection, administered at least once, proved truly effective in preventing the expression of clinical signs of furunculosis and reducing mortality rates. A single intraperitoneal administration provided protection for up to 2352 degree-days, equivalent to approximately 5 months in water at 16°C. However, intraperitoneal vaccination may lead to reduced growth in the fish due to resultant intraperitoneal adhesions. Additionally, protocols incorporating booster doses via intraperitoneal injection demonstrated efficacy regardless of the administration route of the primary vaccination. Nevertheless, the use of booster vaccinations via the intraperitoneal route did not confer any significant advantage over a single intraperitoneal injection in terms of efficacy.

Hong Guo Ginseng Guo (HGGG) protects against kidney injury in diabetic nephropathy by inhibiting NLRP3 inflammasome and regulating intestinal flora

BackgroundDiabetic nephropathy (DN) is one of the most serious complications of diabetes which leads to end-stage renal failure and approximately one-third of patients need dialysis. There is still a lack of effective and specific treatment for DN. Searching new drugs from natural foods is an alternative approach to treat diabetes and its complications. Hong Guo Ginseng Guo (HGGG), a berry with palatability and nutritional benefits, has exhibited medicinal properties to mitigate the progression of DN. PurposeThis study investigates the effects of HGGG on streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats and elucidates the mechanisms underlying its reno-protective and diabetes management benefits. MethodsThe LC-MS spectra method identified the primary ingredients in HGGG. To induce DN, male Sprague-Dawley (SD) rats received a single intraperitoneal injection of 75 mg/kg STZ. Over an eight-week treatment period, we assessed biochemical parameters including blood glucose, urine albumin-to-creatinine ratio (UACR), blood urea nitrogen (BUN), and urine N-acetyl-beta-d-glucosaminidase (NAG). Tissue pathology was examined using Masson's trichrome, Periodic Acid-Schiff (PAS), and Hematoxylin-Eosin (H&E) stains. We analyzed pro-inflammatory mediators and tissue fibrosis extent using Western blotting and immunohistochemistry. Gut microbiota composition was characterized via 16S rDNA sequencing. ResultsSeventeen chemical compounds were identified, with lobetyolin, luteolin, and rutin highlighted as the primary active elements. HGGG extract appeared to confer renal protection, demonstrated by improvements in UACR, BUN, and urine NAG levels. The reno protective effects in HGGG-treated DN rats were linked to reduced renal fibrosis and inhibition of the NLRP3 inflammasome. Additionally, HGGG administration improved gut barrier integrity and altered the gut microbiota in DN rats, increasing the relative abundance of beneficial bacteria known for regulating polyamines and producing short-chain fatty acids (SCFAs), including Ruminococcus, Barnesiella_sp, Anaerovoracaceae, and Prevotellaceae_NK3B31. Meanwhile, treatment with HGGG decreasing the presence of Oscillospira, potential pathogens responsible for producing lipopolysaccharide (LPS). ConclusionHGGG has potential as a beneficial fruit for managing diabetes and its associated complications through modulation of the gut microbiota.

Role of Adenosine Receptor Agonist in a Rat Model of Diabetic-Induced Osteoporosis

Abstract Background Diabetic osteoporosis is caused by chronic hyperglycemia, oxidative stress, advanced glycation end products accumulation and microvascular changes. All these alter signaling pathways involved in bone metabolism. Adenosine receptors (ARs) are expressed in the bone and might play a role in bone homeostasis. Recent data reveal that A2AAR plays a key role in bone homeostasis and regeneration. However, whether it has a role in treatment of osteoporosis induced by diabetes has not been reported. Objective The aim of the present study was to evaluate the effect of CGS-21680, an A2A adenosine receptor agonist, in ameliorating osteoporosis induced by diabetes in a rat model. Materials and Methods Forty adult male Albino-rats were allocated into four groups: Group I: control group; Group II: untreated diabetic induced osteoporosis group; Group III: insulin treated diabetic-induced osteoporosis group; Group IV: adenosine receptor agonist treated diabetic-induced osteoporosis group. Diabetes was induced by a single intraperitoneal injection of STZ at a dose of 40 mg/Kg body weight. At the end of the study the bone marker osteocalcin, serum glucose, insulin, tumor necrosis factor-α, malondialdehyde, glutathione peroxidase, calcium and phosphorus were measured, and bone histopathological analysis was done. Results Compared with the untreated diabetic groups, the A2A adenosine receptor agonist treated group showed less bone loss, which was revealed by the increased cortical bone thickness and trabecular thickness. In addition to decreased oxidative damage and inflammation. Conclusion The decreased oxidative stress and inflammation in the A2A adenosine receptor agonist treated group supports a beneficial effect of A2AAR stimulation in treatment of diabetic induced osteoporosis, which was demonstrated by the improvement in bone microarchitecture.

Effects of Memantine on Cognitive Flexibility in a Valproic Acid Rat Model of Autism

Abstract Autistic children frequently struggle with cognitive flexibility. The potential molecular mechanism underlying cognitive inflexibility remains unclear. Decreased level of brain-derived neurotrophic factor (BDNF), which plays a vital role in neural development and synaptic plasticity may have a role. This study aimed to investigate the effects of memantine on (BDNF) expression in hippocampus of prenatal VPA exposed rats, and its consequent effects on cognitive flexibility. Pregnant female rats received a single intraperitoneal injection of VPA (600 mg/kg) on gestational day 12.5 to induce autistic-like behaviors in their offspring. Afterwards, the 23-day-old male Wistar rat pups received daily intraperitoneal injections of memantine (20 mg/kg) for 4 weeks. The prenatal VPA-exposed rats exhibited reduced cognitive flexibility in the attentional set- shifting task (ASST) reflecting ASD-associated cognitive flexibility deficits, a common ASD- associated problem with accompanied reduction in hippocampal BDNF. The defective performance in ASST was more prominent in the reversal stages. Memantine associated increased hippocampal BDNF could alleviate cognitive inflexibility in ASD. This study draws attention to the potential favorable effect of memantine on cognitive performance in autistic subjects.

The Protecting Role of Black Seed Oil and Its Nano-Formulation in LPS-Induced Acute Kidney Injury in Mice: Evaluation of Oxidative Stress, Biochemical & Molecular Parameters.

Acute kidney injury (AKI) is a medical concern that is accompanied by the rapid deterioration of kidney function. It can be triggered by lipopolysaccharide (LPS) of gram-negative bacteria as it activates a complicated immune response, resulting in widespread inflammation and potential organ dysfunction. Black seed oil (BSO) is rich in beneficial constituents and has been widely used owing to its nutritional advantages. This research is aimed to investigate the potential protective effects of BSO and its nano-formulation on AKI induced by LPS. It also aimed to compare their anti-inflammatory activity with indomethacin, a known synthetic anti-inflammatory drug. Forty-eight mice were placed randomly into 8 groups. A single intraperitoneal (i.p.) injection of 2.5 mg/kg B.W. of LPS was used to trigger inflammation, and pretreatment with BSO and its nano-formulation was at 0.2 mL/kg/day for 14 consecutive days. Indomethacin was used as a reference drug and its efficacy was tested alone or in combination with BSO at lower doses. Renal function was assessed using urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Also, oxidative and inflammatory markers were assessed by measuring levels of reduced glutathione (GSH), nitric oxide (NO), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), and toll-like receptor-4 (TLR-4). Histopathological examination of the kidney tissues was also performed. The study showed that BSO and its nano-formulation had anti-inflammatory effects comparable to or better than those of indomethacin. They greatly decreased the oxidative stress and inflammatory markers induced by LPS. Their protective effect against pathological alterations in kidney tissues was significantly noticed. BSO and its nano-formulation could be used as nephroprotective and anti-inflammatory supplements.

Chlordiazepoxide reduces anxiety-like behavior in the adolescent mouse elevated plus maze: A pharmacological validation study

This report evaluates the effects of chlordiazepoxide, a benzodiazepine commonly prescribed to manage anxiety-related disorders in adolescent/pediatric populations, on elevated plus maze (EPM) performance in juvenile mice. This approach was taken because chlordiazepoxide produces anxiolytic-like effects in multiple models in adult rodents, however, less is known about the behavioral effects of this benzodiazepine in juveniles. Thus, we administered a single intraperitoneal injection of chlordiazepoxide (0, 5, or 10 mg/kg) to postnatal day 35 male C57BL/6 mice. Thirty minutes later, mice were allowed to explore the EPM for 5-min. We found that chlordiazepoxide-treated mice (5 and 10 mg/kg) spent more time exploring the open arms of the EPM. No differences in velocity (cm/s) or distance traveled (cm) were observed between the groups. These results indicate that chlordiazepoxide induces anxiolytic-related behavior in adolescent male mice.

Striking Long Term Beneficial Effects of Single Dose Psilocybin and Psychedelic Mushroom Extract in the SAPAP3 Rodent Model of OCD-Like Excessive Self-Grooming.

Obsessive compulsive disorder (OCD) is a highly prevalent disorder that causes serious disability. Available treatments leave 40% or more of people with OCD significantly symptomatic. There is an urgent need for novel therapeutic approaches. Mice that carry a homozygous deletion of the SAPAP3 gene (SAPAP3 KO) manifest a phenotype of excessive self-grooming, tic-like head-body twitches and anxiety. These behaviors closely resemble pathological self-grooming behaviors observed in humans in conditions that overlap with OCD. Following a preliminary report that the tryptaminergic psychedelic, psilocybin, may reduce symptoms in patients with OCD, we undertook a randomized controlled trial of psilocybin in 50 SAPAP3 KO mice (28 male, 22 female). Mice that fulfilled inclusion criteria were randomly assigned to a single intraperitoneal injection of psilocybin (4.4 mg/kg), psychedelic mushroom extract (encompassing the same psilocybin dose) or vehicle control and were evaluated after 2, 4 and 21 days by a rater blind to treatment allocation for grooming characteristics, head-body twitches, anxiety and other behavioral features. Mice treated with vehicle (n=18) manifested a 118.71±95.96 % increase in total self-grooming (the primary outcome measure) over the 21-day observation period. In contrast, total self-grooming decreased by 14.60%±17.90% in mice treated with psilocybin (n=16) and by 19.20±20.05% in mice treated with psychedelic mushroom extract (n=16) (p=.001 for effect of time; p=.0001 for time × treatment interaction). 5 mice were dropped from the vehicle group because they developed skin lesions; 4 from the psilocybin group and none from the psychedelic mushroom extract group. Secondary outcome measures such as head-body twitches and anxiety all showed a significant improvement over 21 days. Notably, in mice that responded to psilocybin (n=12) and psychedelic mushroom extract (n=13), the beneficial effect of a single treatment persisted up to 7 weeks. Mice initially treated with vehicle and non-responsive, showed a clear and lasting therapeutic response when treated with a single dose of psilocybin or psychedelic mushroom extract and followed for a further 3 weeks. While equivalent to psilocybin in overall effect on self-grooming, psychedelic mushroom extract showed superior effects in alleviating head-body twitches and anxiety. These findings strongly justify clinical trials of psilocybin in the treatment of OCD and further studies aimed at elucidating mechanisms that underlie the long-term effects to alleviate excessive self-grooming observed in this study.

Antidiabetic Effects of Foeniculum vulgare in Alloxan-induced Diabetic Male Rats

Background &amp; objective: Diabetes mellitus (DM) has become one of the most challenging health problems of the 21st century. Foeniculum vulgare (Mouri in Bengali), an ancient culinary herb, is known to reduce blood glucose levels thus reducing the risk of diabetes. This study was done to observe the antidiabetic role of Mouri in alloxan-induced diabetic male rats. Methods: This experimental study was carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC), Dhaka from July 2018 to June 2019. A total of 30 healthy Wistar albino male rats, 90-120 days old, weighing between 150-180g were included in the study. After acclimatization for 14 days, they were divided into two groups: the control group (Group A) and the experimental group (Group B – diabetic rats treated with Mouri). The control group was again subdivided into Group A1 (normal control group) and Group A2 (alloxan-induced diabetic control group). Each of these groups consisted of 10 rats. All the rats received a basal diet for 21 days. In addition to the basal diet, Group A2 and Group B received a single intraperitoneal injection of alloxan 140 mg/kg on day 1 to induce diabetes. Moreover, Group B received Mouri extract 150 mg/kg/day orally for 21 consecutive days starting from day 1 of the study period. After 12 hours of fasting, blood samples were collected from the tail veins of every rat on day 1 for estimation of Fasting Blood Glucose (FBG) and serum ALT levels. On day 4 FBG levels of all the rats were measured once again. Then all the rats were sacrificed on day 22 and their blood samples were collected from the heart. The outcome variables, such as FBG level, serum levels of insulin, were measured and compared among the study groups. The pancreatic tissue was also collected and histopathology was done by standard laboratory procedure to study their histologic architecture. Result: In this study, fasting blood glucose level in diabetic rats treated with Mouri at the endpoint of the study (on day 22) was significantly lower (5.51 ± 0.47 mmol/L) than that in alloxan-induced diabetic control (13.52 ± 0.76 mmol/L) (p &lt; 0.001) and was almost equal to that in normal control (5.38 ± 0.55 mmol/L) (p = 0.891). The serum insulin level in diabetic rats treated with Mouri (11.52 ± 0.84 mmol/L) was almost similar to that of normal control (12.46 ± 1.07 mmol/L) on day 22, whereas it was much higher than that in alloxan-induced diabetic control (8.51 ± 0.68 mmol/L) (p &lt; 0.001). Histological study of pancreases of the rats, revealed extravasation of blood in the pancreatic acini, reduced area of islets of Langerhans with atrophy, vacuolation, degeneration, and pyknosis of β-cell nuclei and centrilobular necrosis in the alloxan-induced diabetic control rats. Conclusion: Mouri (Foeniculum vulgare) improves the glycemic status of the alloxan-induced diabetic rats. Ibrahim Card Med J 2023; 13 (1&amp;2): 53-59

Effects of empagliflozin on gonadal functions of hyperglycemic male wistar rats.

Empagliflozin (EMPA) showed antiapoptotic, oxidative and anti-inflammatory potential effect. EMPA attenuates the inflammation and oxidative stress biomarkers in patients with heart failure while significantly decreases the malondialdehyde (a lipid peroxidation marker) levels in the plasma of diabetic patients. The present study examined the effects of moderate hyperglycemia on reproductive function. Sixty male Wister rats ‎ were divided and randomly allocated into four groups of 15 animals each‎‎. Diabetes was induced by a single intraperitoneal injection of a prepared solution containing STZ diluted in 0.1 M sodium citrate buffer (pH 4.5) at a dosage of 40 mg/kg body weight in selected in groups II and III for seven days before starting the treatment with EMPA. The current study revealed that EMPA for eight weeks prevented testicular high glucose-induced oxidative stress markers such as penile nitric oxide (NO), glutathione peroxidase (GPX) and total anti-oxidant capacity (TAC) in STZ-induced hyperglycemia in a rat model. In addition, EMPA ameliorated the high levels of endogenous Interleukin-6 (IL-6) present in gonads in response to an acute inflammatory found in the hyperglycemic STZ-induced rats. The present study further suggested the protective effects of EMPA and how it has a beneficial role and can effectively attenuate hyperglycemia-induced testicular oxidative damage and inflammatory markers as well as androgen dependent testicular enzymes activity as a protective role against the consequences of hyperglycemia and male sub-infertility.

FEATURES OF THE TOPOGRAPHY AND NUMBER OF SBA+-В-LYMPHOCYTES IN THE MESENTERY OF THE INTESTINE IN NORMAL CONDITIONS AND DURING THE FORMATION OF THE ADHESION PROCESS

The study of the structural organization of the peritoneum as an immunocompetent organ will contribute to the solution of practical tasks, namely factors that control immune local and systemic reactions in the body. The question of the presence of these cells and their topography by the method of lectin histochemistry in the tissues of the peritoneum at the time of its formation, the peculiarities of the structure in different periods of onotogenesis in the norm and under the influence of endo- and exogenous factors remains not fully investigated. Carbohydrate specificity is used as a criterion for the functional classification of lectin receptors on the surface of cells, which indicates the processes of adhesion to various molecules, including fibrin and immune complexes. The aim of our study was to determine the peculiarities of the topography and the number of B-lymphocytes of the intestinal mesentery in rats in normal conditions and during the adhesion process with the help of soy lectin (SBA). The process of adhesion formation in rats of the II group was simulated by a single intraperitoneal injection of 0.5 ml of a 20% talc suspension into the area pelvis according to the method of Volyanska O.G. (2013). Animals were removed from the experiment 7, 14 and 21 days after the injection. Detection of lymphocytes that differ phenotypically according to carbohydrate residues was performed using soy lectin (SBA). The number of immunocompetent cells per standard area of 1000 μm2) was calculated.The morphology, topography and number of SBA+-lymphocytes, identified as B-lymphocytes, in the intestinal mesentery, as one of the derivatives of the peritoneum, are described. An increase in the number of SBA+ lymphocytes indicates the activation of the nonspecific humoral link of immunity, which is associated with excessive deposition of fibrinoid and affects the morphofunctional state of the peritoneum and its derivatives. Probably, lymphoid tissue associated with serous membranes (SALC) gives rise to the origin of B1-lymphocytes and is the place of their constant renewal. The leakage of fibrin leads to the formation of fibrin plaques, which are pathogenetically capable of changing the structural barrier between the connective tissue and the vessels of the peritoneum, which at the moment remains insufficiently studied. Quantitative studies of the accumulation of fibrin layers by the method of lectin histochemistry are planned.

Potentiating effect of AMD3100 on bone morphogenetic protein-2 induced bone regeneration

BackgroundAMD3100, a CXCR4 antagonist, is currently prescribed for activating the mobilization of hematopoietic stem cells. Recently, AMD3100 was shown to potentiate bone morphogenetic protein-2 (BMP-2)-induced bone formation by stimulating the trafficking of mesenchymal cells. However, optimization of the strategic combination of AMD3100 and BMP-2 has not yet been clearly established. The purpose of this study was to evaluate the effect of AMD3100 on BMP-2-induced bone regeneration in vitro and in a mouse calvarial defect healing model.MethodsIn vitro osteoblastic differentiation and cell migration after sequential treatments with AMD3100 and BMP-2 were analyzed by alkaline phosphatase (ALP) activity, ALP staining, and calcium accumulation. Migration capacity was evaluated after treating mesenchymal cells with AMD3100 and/or BMP-2. A critical-size calvarial defect model was used to evaluate bone formation after sequential or continuous treatment with AMD3100 and BMP-2. The degree of bone formation in the defect was analyzed using micro-computed tomography (micro-CT) and histological staining.ResultsCompared with single treatment using either AMD3100 or BMP-2 alone, sequential treatment with AMD3100 followed by BMP-2 on mesenchymal cells increased osteogenic differentiation. Application of AMD3100 and subsequent BMP-2 significantly activated cell migration on mesenchymal cell than BMP-2 alone or AMD3100 alone.Micro-CT and histomorphometric analysis showed that continuous intraperitoneal (IP) injection of AMD3100 resulted significantly increased new bone formation in BMP-2 loaded scaffold in calvarial defect than control groups without AMD3100 IP injection. Additionally, both single IP injection of AMD3100 and subsequent BMP-2 injection to the scaffold in calvarial defect showed pronounced new bone formation compared to continuous BMP-2 treatment without AMD3100 treatment.ConclusionOur data suggest that single or continuous injection of AMD3100 can potentiate BMP-2-induced osteoblastic differentiation and bone regeneration. This strategic combination of AMD3100 and BMP-2 may be a promising therapy for bone regeneration.

Investigating the Possible Ameliorating Impact of Black Seed (Nigella sativa) Hydroethanolic Extract on Liver and Brain Tissue in a Rat Model of Polycystic Ovary

Background: Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder in women of reproductive age, which may affect various organs, including the brain and liver. Objectives: This study aimed to investigate the potential ameliorating effects of black seed (Nigella sativa) hydroethanolic extract on the liver and brain tissues in a rat model of polycystic ovary. Methods: In this experimental study, eighteen female rats were divided into three groups: control (PCO rats on day 0 after induction of PCO), vehicle (PCO rats receiving saline via gavage for 28 days), and black seed extract (BSE) (PCO rats receiving BSE via gavage for 28 days). Polycystic ovary was induced by a single intraperitoneal injection of 2 mg/kg estradiol valerate. Liver tissue was evaluated for the average number of damaged hepatocytes (segmented nucleus and cytoplasm shrinkage), number of Kupffer cells, and number of lipid droplets, while brain tissue was assessed for vacuolization, apoptosis, and cell shrinkage. Results: In the BSE group, liver weight significantly decreased, while brain weight increased compared to the vehicle and control groups. Moreover, there was a significant decrease in the number of damaged hepatocytes and Kupffer cells in the BSE group compared to the vehicle group in the liver tissue. In the brain tissue, there was a significant reduction in the number of vacuolations in the BSE group compared to the vehicle group. Conclusions: Black seed extract demonstrated potential ameliorating effects on the adverse impacts of PCO in the liver (reducing damaged hepatocytes and Kupffer cells) and brain (reducing vacuolations). Further histologic and molecular analyses are needed to investigate the protective effects of BSE thoroughly.

Histopathological Changes in a Rat Model of Diabetic Neuropathy

This study was done to investigate the histopathological Changes in a Rat Model of Diabetic Neuropathy. The 24 male rats used in this investigation were split into two groups of 12 animals. The first group (G1), which consisted of healthy individuals, was given standard saline. Normal saline was administered after G2 (STZ group) received STZ at a dosage of 60 mg/kg. After rats were starved overnight, a single intraperitoneal injection of 60 mg/kg of freshly produced STZ was given to induce diabetes. (0.1 M, pH 4.5) Sodium Citrate Buffer was used to dissolve STZ. On the third day after the injection of STZ, a digital glucometer was used to measure the blood glucose levels of 12-hour fasting rats; hyperglycemia was defined as values greater than 250 mg/dl. In order to assess neuropathic pain, cold allodynia was calculated by counting the number of times the foot withdrew in response to cold stimuli applied to the back of the hand. The sciatic nerve was carefully removed after the sacrifice (after 2 months) and preserved in 10% formalin for histopathological study. Normal blood glucose levels were maintained in the control rats throughout the study. However, G2 exhibited much greater FBG levels than healthy animals. In the 2-month study, the G2 maintained FBG levels above 250 mg/dl. The score for severity of STZ on sciatic nerves showed a significant difference between treated group as compared with G1. No paw reactions were seen when intact animals were subjected to plantar surface acetone. The experimental groups did not show any notable reactions to acetone on the tenth day after the diagnosis of diabetes. On days 20, 30, 40, 50 and 60 after diabetes confirmation, there were significant differences in paw withdrawal frequency between the G1 and G2 (p&lt;0.001). Within the control group, nerve fibres were found to be regularly arranged and there was no evidence of axonal swelling. However, in the G2 group, nerve fibres were found to be significantly disorganised, and there was a notable increase in the number of Schwann cells in the sciatic nerves, suggesting damage, in comparison to the control group. In conclusion, potentially via antinociceptive, antihyperglycemic, antioxidant, and neuro-regeneration boosting pathways in STZ-induced diabetic peripheral disease.