Dysfunction In Rats Research Articles

Neuroprotective Role of Zingerone: Investigating the Effective Doses of Zingerone in Lead Acetate-Induced Brain Dysfunctions in Rats

This experiment was designed to determine the effective dose of zingerone against the sublethal dose of lead acetate that induced brain dysfunctions in rats through using different successive doses of zingerone on some parameters related to oxidative stress for 28 days. Thirty-six adult male rats were randomly selected and divided equally into six experimental groups and treated for 28 days as follows: Control group: administered (orally) sterile distilled water. G1 group: administered (orally) (1/280 from LD50) of lead acetate and treated with 25mg/kg for 4 weeks, the rats were then dissected. G2 group: administered (orally) (1/280 from LD50) of lead acetate and treated with 50mg/kg for 4 weeks, the rats were then dissected. G3 group: administered (orally) (1/280 from LD50) of lead acetate and treated with 100mg/kg for 4 weeks, the rats were then dissected. G4 group: administered (orally) (1/280 from LD50) of lead acetate and treated with 150mg/kg for 4 weeks, the rats were then dissected. G5 group: administered (orally) (1/280 from LD50) of lead acetate and treated with 200mg/kg for 4 weeks, the rats were then dissected. Blood samples were collected, by heart punched under anesthesia, at the end of the experiment for measuring the serum malondialdehyde, neuroglobulin, and dopamine concentrations. The result showed a significant (P<0.05) positive correlation between successive doses of zingerone and dopamine and neuroglobulin concentrations, while a significant (P<0.05) negative correlation between successive doses of zingerone and the concentration of malondialdehyde in all animals that are treated with lead acetate compared to the control group. Concluded from this research show that the zingerone has potent antioxidants and neuroprotective effects at the dose 125 mg/kg BW may result in a significant improvement of the neurotransmitter levels and decrease in the production of oxidative stress to the brain tissue.

HISTOLOGICAL CHANGES IN THE RAT SPLEEN IN THE EARLY STAGES OF EXPERIMENTAL STREPTOZOTOCIN-INDUCED DIABE-TES MELLITUS

Diabetes is a systemic disorder that has a significant impact on a number of different organ systems within the body. Studying changes in the spleen in diabetic rats aids in understanding these changes and their effect on immune function. The objective of the study is to investigate the characteristics of morphological changes in the structural components of the spleen in the early stage of experimental diabetes.Results. Morphological changes in the spleen during the early stages of streptozotocin-induced experimental diabetes mellitus were observed. Diabetes was induced by a single intraperitoneal injection of streptozotocin. Histological examination of the spleen was conducted 14 and 28 days after diabetes induction. In healthy rats, the spleen exhibited a normal structure with a clear distinction between red and white pulp. Morphometric analysis showed that lymphoid nodules had a diameter of (445.92±12.6) μm and a marginal zone thickness of (76.22±5.12) μm. After 14 days of experimental diabetes, histological preparations revealed reduced lymphoid nodules of white pulp with a diameter of (435.83±14.28) μm and germinal centers (139.97±5.74) μm. After 28 days, lymphoid nodules further decreased to (392.37±10.29) μm, and germinal centers - to (125.93±5.71) μm. The width of the periarterial lymphoid sheaths decreased to (67.91±3.62) μm, indicating early changes in T-cell zones.Conclusion. During the initial stages of diabetes mellitus in experimental settings, notable structural modifications occur in the spleen. Specifically, there is a reduction in the size of lymphoid nodules, germinal centers, and various zones of the spleen, as well as a decrease in the density of lymphocytes. These alterations may suggest a severe immunological dysfunction in rats used for experimentation.

Rosiridin Protects Against Aluminum Chloride-Induced Memory Impairment via Modulation of BDNF/NFκB/PI3K/Akt Pathway in Rats

Background and Objectives: Rosiridin is a monoterpene with outstanding monoamine inhibitory activity that is useful to treat depressive episodes and rapid-onset dementia. The current investigation aims to evaluate the neurologically protective impact of rosiridin, which opposes aluminum chloride (AlCl3) and causes memory dysfunction in rats. Materials and Methods: Memory impairment was developed in Wistar rats by administering AlCl3 (100 mg/kg p.o.) orally for 42 days and then supplemented with rosiridin at 10 and 20 mg/kg/p.o. Upon completion of the investigation, the behavior factor was performed utilizing the Y-maze, Morris Water Maze, and open field tests. Estimating numerous biological factors, such as nitric oxide (NO), oxidative stress (malondialdehyde MDA), acetylcholinesterase (AChE), butyrylcholinesterase levels (BuChE), antioxidants (glutathione GSH, catalase CAT, and superoxide dismutases SODs) and neurotransmitter (serotonin-5HT, dopamine-DA, acetylcholine-Ach) in the brain. Furthermore, interleukin-6 (IL-6), IL-1β, tumor necrosis factor (TNF-α), brain-derived neurotrophic factor (BNDF), nuclear factor kappa B (NFᴋB), phosphatidylinositol 3-kinase (PI3K), and pAkt were assessed in the diffused brain cells. Results: The rosiridin-treated group significantly improved in terms of behavioral parameters, including in the Y-maze, Morris Water Maze, and open field tests. Further, rosiridin restored biochemical parameters, including NO, oxidative stress AChE, BuChE, antioxidants, neurotransmitters, IL-6, IL-1β, TNF-α, BNDF, NFᴋB, PI3K, and pAkt compared to AlCl3. Conclusions: The current investigation reveals that rosiridin could ameliorate the impairment of memory that AlCl3 causes in rats via improvements in behavioral and restored biochemical parameters.

Effect of ethyl acetate extract from Usnea longissima on chemotherapy-associated multiple organ dysfunction in rats

BackgroundThe toxic effects of doxorubicin and cisplatin in various organs have been associated with oxidative stress. Studies have shown that Usnea longissima has strong antioxidant effects. This study aimed to investigate the protective effect of ethyl acetate extract from Usnea longissima (ULE), which is known to have strong antioxidant effects, on chemotherapeutic-induced heart, kidney, liver, and ovarian toxicity. MethodsAlbino Wistar female rats were divided into five groups (12 rats per group): healthy (HG), doxorubicin (DOX), Cisplatin (CIS), Doxorubicin+ ULE (DULE), Cisplatin+ ULE (CULE). In this experiment, ULE was given 100 mg/kg orally. After 1 hour, 2.5 mg/kg doxorubicin and 2.5 mg/kg cisplatin were administered intraperitoneally. Drug treatments continued once a day for seven days. At the end of seven days, six rats from each group were euthanized and heart, kidney, liver, and ovary tissues were analyzed biochemically. The remaining rats were left in the laboratory with male rats for 45 days for reproduction. ResultsULE inhibited chemotherapeutic-induced increase in malondialdehyde, tumor necrosis factor-alpha, and interleukin 6 and a decrease in total glutathione in liver, kidney, and ovarian tissues. ULE also inhibited the increase of blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase in serum. ULE treatment had no protective effect against doxorubicin and cisplatin cardiac toxicity. On the other hand, ULE also decreased the delay in pregnancy induced by chemotherapy. ConclusionULE may be considered an adjuvant therapy in patients receiving chemotherapy to reduce liver, kidney, and ovarian toxicity.

Andrographolide prevents acute hyperammonemia-induced motor dysfunction in rats. Evidences for its mechanism of action

Andrographolide prevents acute hyperammonemia-induced motor dysfunction in rats. Evidences for its mechanism of action

AnMei Decoction Ameliorating Cognitive Impairment in Rats with Chronic Sleep Deprivation by Mitigating Hippocampal Neuroinflammation and Restoring Synaptic Architecture

AnMei Decoction (AMD) is a renowned herbal prescription that has been widely demonstrated to have positive therapeutic effects on sleep disorders, depression, and cognitive impairments. However, the molecular mechanisms underlying AMD's resistance to sleep deprivation-induced cognitive impairment remain to be further investigated. To clarify whether AMD may alleviate neuroinflammation by inhibiting NLRP3/Caspase1 signaling pathway and repair neuronal damage by regulating BDNF/TrkB pathway, thereby improving cognitive dysfunction in rats with chronic sleep deprivation. LC-MS/MS was used to detect the active components in AMD. After behavioral tests, HE staining, Nissl staining, immunofluorescence, immunohistochemistry, transmission electron microscopy, and Golgi staining were performed to assess the effects of AMD on chronic sleep deprivation. Western blot was used to detect the expression of hippocampal proteins NLRP3, Caspase-1, BDNF, p-TrkB, TrkB, Bax, Bcl-2, GAP43, PSD95, SNAP25, SYN, STX1A, and VAMP2. Hippocampal transcriptome sequencing was employed to observe differentially expressed genes after AMD intervention. A total of 15 active components were identified from the AMD extract. AMD effectively improved the exploration and learning and memory abilities of sleep-deprived rats. AMD reduced neuroinflammation by inhibiting the NLRP3/Caspase-1 pathway and repaired neuronal damage by regulating the BDNF/TrkB pathway. Simultaneously, AMD upregulated the expression of BDNF, p-TrkB, Bcl-2, GAP43, PSD95, SNAP25, SYN, STX1A, and VAMP2 proteins and inhibited the expression of NLRP3, Caspase-1, and Bax proteins. Analysis of GO and KEGG pathway enrichment for the differentially expressed inflammation-related pathways may be involved in the therapeutic mechanism of AMD on sleep deprivation. AMD can effectively inhibit the NLRP3/Caspase1 signaling pathway to alleviate neuroinflammation, regulate the BDNF/TrkB pathway to maintain hippocampal neuronal viability, repair synaptic structural damage, and improve cognitive impairment in the sleep deprivation model.

Selenium ameliorates oxidized phospholipid-mediated testicular dysfunction and epididymal sperm abnormalities following Bisphenol A exposure in adult Wistar rats.

Bisphenol A (BPA) is an endocrine-disrupting compound extensively utilized in the production of polycarbonate polymers and epoxy resins that, upon exposure, pose a significant threat to male reproductive health because of its estrogenic properties. Accumulating evidence suggests that BPA exposure disrupts the normal process of spermatogenesis, alters testicular morphology and function, and interferes with testicular steroidogenesis and hormonal signaling. However, the precise mechanism by which BPA affects testicular function remains unclear. In this study, we explored the mechanism underlying BPA-induced testicular abnormalities and evaluated the protective effects of Selenium (Se). Thirty-two adult male albino Wistar rats were divided into four groups, and BPA was administered at 50mg/kg body weight, with or without Se supplementation, for 30 days. Se supplementation (2.5mg/kg body weight) was initiated 1 week before BPA administration. BPA administration resulted in alterations in testicular architecture, characterized by basement membrane disintegration in the seminiferous tubules, reduced spermatogenic cell counts, and increased interstitial tubule noncellular space. Furthermore, BPA exposure increased the levels of oxidized phospholipids, lipid peroxides, and hydroxyl radicals and decreased the activities of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. In addition, BPA significantly reduced the activities of 3β- and 17β-hydroxysteroid dehydrogenases, interfering with testicular steroidogenesis. In rats, coadministration of Se and BPA reduced the levels of oxidized phospholipids and increased the activities of antioxidant enzymes, leading to improved testicular function and epididymal sperm parameters, suggesting that Se plays a critical role in alleviating endocrine disruptor-induced testicular dysfunctions in rats.

Sodium arsenite-mediated cellular dysfunctions in rats: modulation by leaf extract of Tridax procumbens

Sodium arsenite-mediated cellular dysfunctions in rats: modulation by leaf extract of Tridax procumbens

A new natural product derived from cyclosorus terminans provides cardiometabolic protection against obese-induced cardiac dysfunction in rats via suppressing mitochondrial dysfunctions and apoptosis

Abstract Background The development of a novel pharmacological target for obesity has long been considered challenging in mitigating the global cardiovascular complications and mortality. Given the cytotoxic effects associated with various anti-obesity drugs, there is growing interest in exploring new natural products as potential sources for bioactive agents to treat obesity-associated diseases with minimal side effects. While Cyclosorus terminans extract has demonstrated anti-diabetic and anti-obese efficacies in adipose-derived stem cells, its cardioprotective effects in high-fat diet (HFD)-induced obese-insulin resistance rat models have never been elucidated. Purpose To examine the effects of long-term Cyclosorus terminans treatment on metabolic, cardiac, and mitochondrial functions and apoptosis in HFD-induced obese-insulin-resistant rat models Methods Male Wistar rats (n=10) were continually fed with HFD and treated with either vehicle (HFV, virgin oil for 2 ml/kg/day, p.o., n=5) or Cyclosorus terminans (HFC, 100 mg/kg/day, p.o., n=5) for 12 weeks. Rats fed a normal diet (NDV, n=5) were used as a control to confirm the development of HFD-induced obesity. The left ventricular ejection fraction (LVEF) and the ratio between early (E) and late atrial (A) ventricular filling velocity were measured using echocardiography, and the homeostatic model assessment for insulin resistance (HOMA-IR) was determined using blood serum. The cardiac tissue was processed to assess mitochondrial reactive oxygen species (ROS) levels, membrane potential (MMP) changes via red/green fluorescence intensity ratio, and apoptotic protein. Results HFV rats became obese and had impaired cardiometabolic function as shown by reducing LVEF, E/A ratio, and increasing HOMA-IR, respectively (Fig. 1A-C). These obese rats also had mitochondrial ROS overproduction, MMP depolarization (reduced red/green ratio), and apoptosis (increased Bax protein expression) (Fig. 1D-F). Treatment with Cyclosorus terminans (HFC) significantly mitigated mitochondrial dysfunction and apoptosis, resulting in cardiometabolic protection in HFD-fed rats (Fig. 1A-F). Conclusion A new natural product derived from Cyclosorus terminans effectively protected the heart against long-term HFD-induced cardiometabolic impairments by reducing mitochondrial dysfunction and apoptosis. These findings demonstrate Cyclosorus terminans as a novel cardiometabolic protection against obesity-related cardiac complications.

Poliumoside inhibits apoptosis, oxidative stress and neuro-inflammation to prevent intracerebroventricular Streptozotocin-induced cognitive dysfunction in Sprague-Dawley Rats: in in-vivo, in-vitro and in-silico study.

Alzheimer's disease (AD) is a severe neurological illness causes cognitive decline and mortality if not treated early. However, the current therapeutic modalities are inefficient to manage the cognitive dysfunction of AD. Therefore, in the present manuscript, we have enumerated the pharmacological benefit of Poliumoside in the Streptozotocin-induced cognitive dysfunction in Sprague-Dawley (SD) rats. Initially, the cognitive dysfunction in rats was induced by the intracerebroventricular administration of Streptozotocin, then rats received PMD (5 mg and 10 mg/kg body weight) was given. Various behavioural analysis, such as Morris water maze (MWM), and object recognition tests (ORT), and locomotor analysis was conducted in PMD treated group. Various biochemical analysis was conducted to analyze the effect of PMD on hippocampus oxidative-nitrosative stress and pro-inflammatory cytokines. MTT assay and annexin V/PI staining was performed to analyse the effect of PMD on the cell viability and neuronal toxicity of PC12 cells, respectively. Molecular docking analysis was also conducted with crystal structure of human AChE. PMD treatment improved cognitive capacity in rats in MWM and ORT. Compared to STZ rats, PMD-treated rats had significantly higher locomotor activity and lower AChE activity. PMD also restores dopamine, 5-HT, and NE levels and reduces metabolic their deactivation as evidenced by increased levels of DOPAC, HVA, 5-HIAA. Nitrite, MDA, SOD, CAT, and GSH levels were restored near normal in PMD-treated rats, reducing hippocampus oxidative-nitrosative stress. Pro-inflammatory cytokines were similarly lowered in PMD-treated rats. In in-vitro studies, PMD did not affect PC12 cell survival at the maximal dose of 10 µM. In addition, PMD concentration-dependently prevents H₂O₂-induced neuronal death in PC12 cells. The in-silico docking analysis showed that the PMD fit snugly into the active site of human AChE by engaging with the anionic domain and the catalytic triad of Trp86, Tyr337, Phe338, and Gly121 residues. In conclusion, our study demonstrated that PMD have significant impact on AD by inhibiting ACheE and restoring neurotransmitter levels, which enhances Ach levels in rats and improves cognitive impairment in STZ rats.

Therapeutic Effects of Proanthocyanidins on Diabetic Erectile Dysfunction in Rats.

The rising occurrence of erectile dysfunction related to diabetes mellitus (DMED) has led to the creation of new medications. Proanthocyanidins (PROs) is a potential agent for DMED. In this study, the DMED rat model was established using streptozotocin (STZ) and erectile function was assessed using apomorphine (APO) in rats. Following this, the rats were subjected to oral treatment with PRO. Then, we evaluated the influence of PROs on DMED rats. The findings suggest that PROs significantly enhance erectile function in DMED rats. PROs modulated glucose and lipid metabolism in DMED rats by decreasing blood glucose and lipid levels while increasing liver glycogen and serum insulin levels. Furthermore, PROs enhanced vascular endothelial function in DMED rats by augmenting nitric oxide (NO) levels and reducing the levels of endothelin-1 (ET-1) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). Additionally, PROs have been shown to elevate testosterone (T) levels, mitigate pathological testicular damage, and enhance sperm concentration and survival rates. Finally, the core targets were screened using network pharmacology, followed by validation through molecular docking, enzyme-linked immunoassay (ELISA), and real-time PCR methodologies. Our findings imply that PROs may treat DMED by elevating AKT1 levels while concurrently diminishing CASP3 levels, thereby effectively regulating the PI3K-Akt signaling pathway. Overall, these results support using PROs as a potential candidate for the treatment of DMED.

Vitamin D3 mitigates myopathy and metabolic dysfunction in rats with metabolic syndrome: the potential role of dipeptidyl peptidase-4.

Metabolic syndrome is associated with vitamin D3 deficiency. This work aims to examine the efficacy of vitamin D3 in inhibiting MetS-induced myopathy and to determine whether the beneficial effects of vitamin D3 are mediated by the inhibition of dipeptidyl peptidase-4 (DPP-4). An in silico study investigated the potential effectiveness of vitamin D3 on the inhibition of the DPP-4 enzyme. An in vitro assay of the DPP-4 inhibitory effect of vitamin D3 was performed. In vivo and over 12 weeks, both diet (with 3% salt) and drinking water (with 10% fructose) were utilized to induce MetS. In the seventh week, rats received either vitamin D3, vildagliptin, a combination of both, or vehicles. Serum lipids, adipokines, glycemic indices, and glucagon-like peptide-1 (GLP-1), muscular glucose transporter type-4 (GLUT-4) content, DPP-4, adenosine monophosphate kinase (AMPK) activities, and Sudan Black B-stained lipids were assessed. Muscular reactive oxygen species (ROS), caspase-3, and desmin immunostaining were used to determine myopathy. MetS-induced metabolic dysfunction was ameliorated by vitamin D3, which also reduced intramuscular glycogen and lipid accumulation. This is demonstrated by the attenuation of MetS-induced myopathy by vitamin D3, decreased oxidative stress, increased desmin immuno-expression, and caspase-3 activity. Our in silico data demonstrated that vitamin D3 is capable of inhibiting DPP-4, which is further supported by biochemical findings. Vitamin D3 increased serum GLP-1, muscular AMPK activity, and GLUT-4 content, whereas the levels of muscular ROS were decreased in MetS. Vildagliptin and its combination with vitamin D3 yielded comparable results. It is suggested that the DPP-4 inhibitory potential of vitamin D3 is responsible for the amelioration of MetS-induced metabolic changes and myopathy.

N-acetylcysteine and zinc sulphate abate di-2-ethylhexyl phthalate-mediated reproductive dysfunction in rats: Focus on oxidative and sex hormone receptors mechanisms

Objective: To investigate the potential of N-acetylcysteine (NAC) and zinc sulphate (ZnSO4) in mitigating reproductive dysfunction caused by di-2-ethylhexyl phthalate (DEHP) in rats and to understand the underlying mechanisms, specifically oxidative stress and sex hormone receptor activity. Methods: Thirty-five male Wistar rats were randomly divided into five equal groups (n=7 per group). Group 1 was administered 0.5 mL of distilled water and served as the control group. Group 2 was given only DEHP (750 mg/kg/day), while group 3, 4 and 5 were given DEHP (750 mg/kg/day) plus NAC (100 mg/kg/day), DEHP (750 mg/kg/day) plus ZnSO4 (0.5 mg/kg/day), and DEHP (750 mg/kg/day) plus NAC (100 mg/kg/day) as well as ZnSO4 (0.5 mg/kg/day), respectively. All treatments lasted for 21 days. Samples were obtained after the rats were sacrificed, and hormones levels in the serum and markers of oxidative stress in the testicles were analyzed using the enzyme-linked immunosorbent assay. The amount of androgen receptors in the testicles was determined by immunohistochemistry, and the susceptibility of testosterone and DEHP to bind to androgen receptor and 5α-reductase was determined by molecular docking studies. Results: DEHP decreased reproductive hormones, testicular antioxidant enzymes, increased malondialdehyde levels, and negatively impacted histology of the pituitary and testes. NAC or ZnSO4 treatment showed a marked improvement in testicular antioxidant status and hormone levels, as well as a positive effect on the histology of the pituitary and testes. The combination of both treatments appeared to be more effective. The affinity of DEHP to bind to androgen receptors may lead to disruption of androgen receptor signaling, which can further result in dysfunction of hormones related to androgen. However, NAC is more likely to form stronger binding interactions with follicle stimulating hormone and luteinizing hormone receptors, as well as gonadotropin-releasing hormone receptors, when compared to DEHP. Conclusions: The possibility that NAC and ZnSO4 could downregulate DEHP-induced sex hormone changes is suggested by their potential to reduce toxicity.

Hesperitin prevents non-alcoholic steatohepatitis by modulating mitochondrial dynamics and mitophagy via the AMPKα-Drp1/PINK1-Parkin signaling pathway

Non-alcoholic fatty liver disease (NAFLD) is becoming a global public health burden, yet effective therapeutic strategies are notably lacking. NAFLD development may be mediated by mitochondrial dysfunction, according to new research. Producing mitochondrial regulators from plant-based substances to treat mitochondrial dysfunction is an appealing approach to treating NAFLD. Hesperetin (HES) is a flavonoid that is found naturally and is a member of the flavanone family. This study aims to clarify the mechanism of HES in preventing NAFLD which is caused by a high-fat diet (HFD). Serum and liver biochemical parameters, liver histology, lipid profiles, and mitochondrial function were evaluated in HFD-induced NAFLD Sprague-Dawley (SD) rats. HES treatment significantly reduced body weight gain, liver weight, and the liver index, while also improving hepatic steatosis, lipid metabolism disorders, and mitochondrial dysfunction in rats with NAFLD. The mechanism was investigated and confirmed using western blot and real-time quantitative polymerase chain reaction (RT-qPCR). We showed that in the liver of NAFLD rats, HES decreased the expression of dynamic-related protein 1 (Drp1), phosphorylated Drp1 at serine-616 (Drp1-pS616) and induced phosphorylated Drp1 at serine-637 (Drp1-pS637), PTEN-induced kinase 1 (PINK1), and E3 Ubiquitin-Protein Ligase Parkin (Parkin) via an AMP-activated protein kinase alpha (AMPKα)-dependent mechanism. Moreover, HES increased the expression of the mitochondrial fusion proteins mitofusin-2 (Mfn2) and optic atrophy 1 (Opa1) while suppressing the expression of fission protein 1 (Fis1). In this work, we identify a unique mechanism by which HES prevents NAFLD from developing. HES may be an attractive potential therapeutic agent to cure NAFLD.

Ketamine induced gut microbiota dysbiosis and barrier and hippocampal dysfunction in rats

Ketamine induced gut microbiota dysbiosis and barrier and hippocampal dysfunction in rats

Liquid chromatography–mass spectrometry profiling of propolis and royal jelly and their ameliorative effects on cadmium-instigated pathological consequences in ovarian tissues of rats

This study was undertaken to identify the bioactive components of propolis (PRO) and royal jelly (ROJ) and their therapeutic influence on attenuating cadmium chloride (CdCl2)-induced ovarian toxicity and dysfunction in rats. The composition of PRO or ROJ was ascertained employing the liquid chromatography–linear ion trap quadrupole–mass spectrometry (LC–LTQ–MS–MS) method. To further evaluate the anti-infertility properties of PRO and ROJ instigated by cadmium (Cd) in vivo, thirty female mature rats (183.3 ± 12.5 g) were randomly assigned into six groups (n = 5 per group). The established animal groups included (I) control, (II) Cd, (III) PRO, (IV) ROJ, (VI) PRO + Cd, and (VII) ROJ + Cd groups. Cadmium exposure disrupted ovarian tissue functions, demonstrating remarkable disorders in progesterone and estrogen. Furthermore, the comet assay exhibited a marked rise in DNA impairment in Cd-exposed rats, implying genotoxicity. Conversely, PRO or ROJ significantly counteracted the Cd-instigated pathophysiological consequences, ameliorating hormonal levels and lessening DNA damage. Critically, histological analysis revealed several anomalies in the ovarian tissues of the Cd-administered group. Interestingly, PRO or ROJ preserved the typical structure of ovarian tissues. Our findings indicate that both PRO and ROJ could be utilized to attenuate the pernicious influences incited by Cd due to their anti-androgenic attributes.

NLRP3 inhibitor combined with Yimusake improves erectile dysfunction in rats with diabetes mellitus through the attenuation of pyroptosis

Erectile dysfunction (ED) is a prevalent complication associated with diabetes mellitus (DM), yet pharmacological treatments for diabetes-related erectile dysfunction (DMED) continue to be inadequate in clinical settings. Our previous studies have indicated that there is a close correlation between ED and pyroptosis, but the specific mechanism remains unclear. In this study, we sought to explore the therapeutic effects of DMED through the modulation of NLRP3, aiming to elucidate its potential molecular mechanisms. The DMED rat model was established via intraperitoneal injection of streptozotocin. The rats were randomly assigned to the control group, the DMED group, the Yimusake group, the MCC950 (NLRP3 inhibitor) group, and the MCC950+Yimusake group. Erectile function of rats was observed by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP). HE staining was performed to observe the histopathological changes in penile; immunofluorescence was performed to measure the level of CD31 (Platelet endothelial cell adhesion molecule-1) in penile. Besides, immunohistochemistry, RT-qPCR and Western blot were performed to demonstrate the expression of NLRP3, caspase-1, IL-1β and eNOS. After treatment with the MCC950 and Yimusake, the number of blood sinusoids and small vessels significantly reduced in penile tissue; NLRP3, caspase-1, IL-1β proteins and mRNA expression decreased, eNOS protein and mRNA expression increased. Compare with the Y group and the MCC950 group, MCC950+Yimusake group had a more significant effect. MCC950 and Yimusake might potentially suppress pyroptosis in the penile tissue of DMED rats by modulating the NLRP3/caspase-1 pathway, thus enhancing erectile function. This discovery could offer a promising therapeutic approach for individuals with DMED.

Pharmacological assessment of delphinidin in counteracting polystyrene microplastic induced renal dysfunction in rats

Polystyrene microplastics (PSMP) are toxic environmental contaminants which can damage various body organs including kidneys. Delphinidin (DEL) is a potential anthocyanidin flavonoid with significant pharmacological benefits. This research was conducted to analyze the protective effect of DEL to avert PSMP prompted renal dysfunction. Rats (n = 24) were divided into 4 separate groups: Control, PSMP (0.01 mgkg−1), PSMP (0.01 mgkg−1) + DEL (25 mgkg−1) and only DEL (25 mgkg−1). Our results showed that PSMP exposure reduced the expressions of Nrf-2 and antioxidant genes while increasing the expression of Keap1. Besides, PSMP intoxication escalated the level of kidney injury markers (urea, KIM-1, creatinine and NGAL) while inducing substantial reduction in the levels of creatinine clearance. Moreover, PSMP significantly reduced the levels of GSH, GST, SOD, HO-1, CAT, GSR, GPx while escalating MDA and ROS. Conversely, inflammatory biomarkers including IL-1β, TNF-α, NF-kB, IL-6 and COX-2 activity were increased due to PSMP intoxication. Our results showed that PSMP administration increased the expressions of Bax and caspase-3 while decreasing the expression of Bcl-2. However, DEL treatment significantly restored the PSMP-induced renal impairments. Therefore, it is suggested that DEL could be used as a therapeutic compound to alleviate PSMP-induced kidney damage in rats, possibly due to its strong pharmacological properties.

GPER Stimulation Attenuates Cardiac Dysfunction in a Rat Model of Preeclampsia.

Preeclampsia poses a substantial clinical challenge, characterized by maternal hypertension, cardiac dysfunction, and persistent cardiovascular risks for both the mother and offspring. Despite the known roles of the estrogen receptor (GPER [G protein-coupled estrogen receptor]) in placental development, its impact on cardiovascular aspects within a preeclampsia animal model remains unexplored. We propose that G-1, a GPER agonist, could have the potential to regulate not only hypertension but also cardiac dysfunction in rats with preeclampsia. To explore the influence of G-1 on preeclampsia, we used the reduced uterine perfusion pressure (RUPP) model. RUPP rats were administered either G-1 (100 µg/kg per day) or hydralazine (25 mg/kg per day). We conducted echocardiography to probe the intricate cardiac effects of G-1. The RUPP rat model revealed signs of hypertension and cardiac dysfunction and alterations in gene and protein expression within placental and heart tissues. G-1 treatment reduced blood pressure and reversed cardiac dysfunction in rats with preeclampsia. In contrast, administration of the vasodilator hydralazine reduced blood pressure without an improvement in cardiac function. In addition, while G-1 treatment restored the levels of sFLT-1 (soluble fms-like tyrosine kinase-1) in RUPP rats, hydralazine did not normalize this antiangiogenic factor. The therapeutic intervention of G-1 significantly mitigated the cardiovascular dysfunction observed in the RUPP rat model of preeclampsia. This discovery underscores the broader significance of understanding GPER's role in the context of preeclampsia-related cardiovascular complications.

Tannic Acid Suppresses Ferroptosis Induced by Iron Salophene Complex in Kidney Cells and Prevents Iron Overload-Induced Liver and Kidney Dysfunction in Rats.

Iron toxicity intricately links with ferroptosis, a unique form of cell death, and is significantly influenced by lipid peroxidation. Despite its critical role in various diseases and drug development, the association between iron toxicity and ferroptosis remains relatively unexplored. Accidental iron ingestion has emerged as a growing concern, resulting in a spectrum of symptoms ranging from gastrointestinal discomfort to severe outcomes, including mortality. This research introduces tannic acid (TA), which contains numerous phenol groups, as a powerful antiferroptotic agent. In male Wistar rats, even a modest dose of TA (7.5mg/kg) significantly curtailed thiobarbituric acid reactive substances (TBARS), a well-established indicator of lipid peroxidation, and mitigated iron accumulation induced by ferrous sulfate (FeSO4) in the liver and kidney. The evidence supporting TA's protective function against iron-triggered liver and kidney dysfunction was substantiated by assessing specifically the levels of blood urea nitrogen (BUN) and alanine aminotransferase (ALT). In cell models using ferroptosis inducers such as iron-salophene (FeSP) and RAS-selective lethal 3 (RSL3), tannic acid (TA) exhibited superior protective capabilities compared to the traditional iron chelator, deferoxamine (DFO). Nrf2 and HO-1, regulators of antioxidant defense genes, are implicated in controlling ferroptosis. The expression of Nrf2 and HO-1 increased with TA treatment in the presence of FeSP, indicating their role in reducing lipid ROS levels. Additionally, TA significantly reduced the heightened levels of COX2, a marker associated with ferroptosis. In summary, the remarkable antiferroptosis activity of TA is likely due to its combined iron-chelating and antioxidant properties. With its safety profile for oral consumption, TA may offer benefits in cases of accidental iron ingestion and conditions like hemochromatosis.