Ahmed A. Sedik

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia, leading to microvascular and macrovascular complications including cardiomyopathy, retinopathy, neuropathy, and nephropathy. This study evaluated the diabetogenic potential and pathological outcomes of two single intraperitoneal doses of streptozotocin (STZ) in male Sprague Dawley rats. Twenty-four rats (200–220 g) were randomly assigned to three groups (n = 8/group): control, STZ 45 mg/kg, and STZ 60 mg/kg. DM was confirmed 72 h post-injection via elevated serum glucose. At the end of the experiment, blood and tissue samples were collected to assess metabolic parameters, lipid profile, liver function, oxidative stress markers, inflammatory cytokines, and histopathological changes. Both doses induced significant hyperglycemia, elevated glycated hemoglobin, and reduced insulin levels. Diabetic rats also showed dyslipidemia, liver dysfunction, increased oxidative stress (↓GSH, ↑MDA), and elevated inflammatory markers (TNF-α, il-6). Histopathological and morphometric analyses confirmed tissue damage and biochemical alterations. Notably, the 60 mg/kg dose produced a more severe and consistent diabetic phenotype, with greater metabolic derangements, oxidative injury, inflammation, and organ pathology compared to the 45 mg/kg dose. These findings suggest that while both doses effectively induce experimental diabetes, 60 mg/kg STZ provides a more robust model for studying DM-associated complications in vital organs.

Hypertension is a significant global health issue that contributes to various cardiovascular and renal diseases. This study investigated the therapeutic potential of Thymus vulgaris essential oil, specifically its primary component, thymol, in mitigating hypertension and related complications. Thirty-two male Sprague-Dawley rats were divided into four groups: normal control, L-NAME-induced hypertension (40mg/kg), L-NAME + high-dose thymol oil (10 mg/kg), and L-NAME + low-dose thymol oil (5 mg/kg). Blood pressure, lipid profiles, renal function markers, inflammatory cytokines (TNF-α, IL-6), apoptosis markers (Annexin-V, Bcl-2), and histopathological changes were evaluated. GC‒MS analysis of Thymus vulgaris essential oil confirmed thymol was the dominant compound (34.21%), suggesting its substantial pharmacological role. In hypertensive rats induced by L-NAME (40 mg/kg), the administration of high-dose thymol oil (10 mg/kg) significantly reduced the systolic and diastolic blood pressures, supporting its antihypertensive efficacy. Additionally, thymol improved lipid profiles by lowering triglyceride, total cholesterol, and LDL levels, while increasing HDL levels. Thymol oil also had protective effects on renal function, as evidenced by decreased levels of urea and creatinine, which are markers of renal dysfunction. Moreover, it reduced the levels of inflammatory markers such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the heart, aorta, and kidneys, indicating its anti-inflammatory properties. Flow cytometry and histopathological analysis revealed that thymol oil significantly reduced apoptosis, as evidenced by decreased Annexin-V expression and increased levels of the anti-apoptotic protein Bcl-2. Tissue damage in the heart, aorta, and renal tissues was markedly restored after administration of high-dose thymol, highlighting its potential for reversing hypertension-induced organ damage. These findings suggest that thymol-rich Thymus vulgaris essential oil offers a multifaceted approach for managing hypertension and its complications, providing both cardiovascular and renal protection.

Acrylamide (ACR) is a hazardous and possibly carcinogenic chemical compound that humans are constantly exposed to in their daily life. ACR passively affect many organ systems, including the cardiovascular system. Cordycepin (Cor) is a bioactive molecule derived from various species in the fungal kingdom, especially the genera Cordyceps and Ophiocordyceps. Cordycepin is known for its large-scale pharmacological activities. This study was conducted to evaluate the potential therapeutic effect of Cor on ACR-induced cardiotoxicity. Thirty-two Sprague‒Dawley rats were randomly divided into four groups (8 rats/group). Group I represented the control group, Group II received ACR (20 mg/kg/day) orally for 27 days, and Groups III and IV represented the control group. Rats received ACR (20 mg/kg) orally concurrently with Cor (10 and 20 mg/kg, b.w.), respectively, for 27 days. Serum cardiac biomarkers, such as cardiac troponin I (cTnI), creatine kinase (CK)-MB and lactate dehydrogenase (LDH), were evaluated. In addition, the antioxidant status and inflammatory response to ACR were evaluated. Moreover, detailed histopathological and ultrastructural observations were conducted. Our findings revealed that rats subjected to ACR presented increased levels of serum cardiac biomarkers, tumor necrosis factor-alpha (TNF-α), interleukin-6 (Il-6), malondialdehyde (MDA), annexin V, and Bax values, and programmed death ligand-1 (PD-L1) and decreased activities of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1) and reduced glutathione (GSH), superoxide dismutase (SOD) and Bcl-2 expression. Conversely, the administration of Cor to rats treated with ACR in a dose-dependent manner succeeded in restoring serum cardiac biomarkers, modulated redox homeostasis and reduced inflammatory and apoptotic biomarkers. Consequently, a marked improvement was observed in the histopathological and ultrastructural images of the heart. In conclusion, Cor provides cardiac protection by inhibiting ACR-induced Nrf2/HO-1 and Bax/Bcl2 signaling failure, hence maintaining heart function. These findings suggest that Cor could be a promising treatment candidate for reducing ACR-induced cardiac damage.

Diabetes mellitus (DM) represents a multifactorial condition linked to hyperglycemia, which, can lead to damage across multiple organs, including the lungs. Nod-like receptor protein-3 (NLRP3)- mediated pyroptosis could contribute to the onset of DM consequences. Several approaches have been established aimed to minimizing the complications associated with DM. Among these, linagliptin and vildagliptin, di-peptidyl peptidase-4 (DPP-4) inhibitors, are known to exert not only antihyperglycemic effects but also additional beneficial biological activities. The current study investigated the impact of linagliptin and vildagliptin on pulmonary function, oxidative stress, and NLRP3-induced pyroptosis in rats. Thirty-two male Sprague Dawley rats were given a 7-day acclimatization period. A single intraperitoneal injection of freshly produced STZ (60 mg/kg) was utilized to develop DM type-1 in rats. Following STZ treatment, all rats were given a 5% glucose solution overnight. Blood glucose levels were monitored in overnight fasted rats 72 h later, with a threshold of 250 mg/dL or higher confirming the onset of DM. The diabetic rats were randomly allocated to treated daily with either vildagliptin (5 mg/kg/p.o.) or linagliptin (5 mg/kg/p.o.) for 30 days. Additionally, the typical control group received merely the vehicle. The findings revealed that vildagliptin improves pulmonary dysfunctions associated with DM by restoring glucose homeostasis, insulin, redox marker levels, and inflammatory indices. Additionally, the NLRP3-pyroptosis-mediated IL-1β was suppressed. Vildagliptin has been shown to mitigate the detrimental effects of diabetes mellitus (DM) on the lungs, as evidenced by a reduction in pathological lung alterations and a decrease in Caspase 3 expression, which is indicative of immunohistochemical changes. In conclusion, pyroptosis triggered by the NLRP3 inflammasome possibly exacerbate diabetic pulmonary injury in rats. Vildagliptin is superior to linagliptin in ameliorating diabetes-induced lung injury primarily via targeting the NLRP3 inflammasome pathway.

Heart failure (HF) represents the final manifestation of various cardiovascular diseases, emerging as a significant global health challenge that impacts over 20 million individuals worldwide. This review provides a comprehensive overview of the latest pharmacological agents developed to address HF, focusing on their effectiveness in alleviating symptoms associated with the condition. It highlights the critical necessity for a more profound understanding of the multifaceted processes and pathways that contribute to HF pathogenesis. The methodology employed in this review demonstrates encouraging outcomes from numerous pharmaceutical agents evaluated for their ability to relieve HF symptoms, showcasing their effectiveness in improving patient experiences. However, a significant gap remains in tackling the fundamental issues underlying HF. The findings emphasize the intricate nature of HF and the obstacles faced in creating therapies that extend beyond mere symptomatic management. Currently, the predominant approach to HF treatment involves targeting the underlying mechanisms of the disease and addressing related neurohumoral imbalances. Despite the growing arsenal of treatments available for HF, patient outcomes continue to be suboptimal. Therefore, this review aims to illuminate potential therapeutic targets for more effective management strategies for HF, ultimately striving to enhance patient prognosis and quality of life.

It is crucial to develop new tactics to prevent ovarian tissue damage in women whose reproductive toxicity is caused by chemotherapy. The present investigation was performed to assess the protective effects of Moringa oleifera (M. oleifera) leaf extract on cyclophosphamide (CP)-induced ovarian damage and reproductive dysfunction. Thirty-two female, healthy Wistar albino rats were randomly assigned to four groups (8 rats/group). The first group was given saline intraperitoneally (i.p.). The second group was given a single dose of CP (200 mg/kg; i.p.). The third and fourth groups were given M. oleifera leaf extract (150 and 250 mg/kg; orally) for 20 days before receiving CP on the final day of the experiment. Hormonal assessments, including follicle stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (ES), were performed 24 h after CP administration. In addition, the antioxidant status and inflammatory response against CP were evaluated. Moreover, detailed histopathological and ultra- structural observations were conducted. For evaluation of statistical significance between different groups; One-way analysis of variance (ANOVA) with Tukey’s post hoc test was adopted. Our findings revealed that rats subjected to CP showed increased levels of FSH, LH, malondialdehyde (MDA), tumor necrosis factor-alpha, and interleukin-8 and decreased levels of ES and glutathione. Pre-treatment with M. oleifera leaf extract (250 mg/kg; orally) was statistically significant (p values < 0.05) as it could improve hormonal changes, oxidative stress indices, and pro- inflammatory mediator levels. Consequently, a marked improvement was observed in the ovarian and uterine architectures, with a normal ovarian reserve and a normal endothelium with normal tubular glands. In conclusion, M. oleifera leaf extract (250 mg/kg) could be used as a pharmaceutical supplement because it protects female rats against CP-induced ovarian damage and reproductive dysfunction.

Diabetic peripheral neuropathy (DPN) poses a significant threat, affecting half of the global diabetic population and leading to severe complications, including pain, impaired mobility, and potential amputation. The delayed manifestation of diabetic neuropathy (DN) makes early diagnosis challenging, contributing to its debilitating impact on individuals with diabetes mellitus (DM). This review examines the multifaceted nature of DPN, focusing on the intricate interplay between oxidative stress, metabolic pathways, and the resulting neuronal damage. It delves into the challenges of diagnosing DN, emphasizing the critical role played by hyperglycemia in triggering these cascading effects. Furthermore, the study explores the limitations of current neuropathic pain drugs, prompting an investigation into a myriad of pharmaceutical agents tested in both human and animal trials over the past decade. The methodology scrutinizes these agents for their potential to provide symptomatic relief for DPN. The investigation reveals promising results from various pharmaceutical agents tested for DPN relief, showcasing their efficacy in ameliorating symptoms. However, a notable gap persists in addressing the underlying problem of DPN. The results underscore the complexity of DPN and the challenges in developing therapies that go beyond symptomatic relief. Despite advancements in treating DPN symptoms, there remains a scarcity of options addressing the underlying problem. This review consolidates the state-of-the-art drugs designed to combat DPN, highlighting their efficacy in alleviating symptoms. Additionally, it emphasizes the need for a deeper understanding of the diverse processes and pathways involved in DPN pathogenesis.

Links between bronchial asthma and depression have recently become a great subject of interest. The present study was carried out to assess the protective role of hesperidin against ovalbumin (OVA)-induced bronchial asthma that is associated with depression in rats, for this purpose, four groups. Rats were sensitized with intraperitoneal administration of 200 μg OVA/10 mg aluminum hydroxide (Al (OH) 3 for 3 consecutive days then at day 11 followed by intranasal challenge with OVA (1.5 mg/kg) at days 19, 20, and 21. Rats were pretreated with hesperidin (100 & 200 mg/kg) 1h before OVA challenge. At the end of the study, behavioral tests, biochemical indices, and histopathological architectures of lung and brain tissues were evaluated. Our findings showed that hesperidin significantly ameliorated the reduction in motor activity, motor coordination, forced swimming, CD4, CD25 and foxp3, interleukin-10 (IL-10), dopamine, serotonin, and neurotrophin-3 (NT3) as well as alleviated the elevation in transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α), iL-5, and immunoglobulin E (IgE). In addition, hesperidin reduced cellular infiltration, alveolar sacs damage, the bronchioles wall disruption, and nuclei pyknosis in neuron cells. Finally, hesperidin may provide protection against OVA-induced asthma and depression. This impact could be mediated in part by its anti-inflammatory and immunoregulatory properties. Graphical abstract