Comparative effectiveness of cervical vs thoracic spinal-thrust manipulation for care of cervicogenic headache: A randomized controlled trial.

BACKGROUND: There is ample evidence supporting the use of different manipulative therapy techniques for Cervicogenic Headache (CgH). However, no technique can be singled as the best available treatment for patients with CgH. Therefore, the objective of the study is to find and compare the clinical effects of cervical spine over thoracic spine manipulation and conventional physiotherapy in patients with CgH. DESIGN, SETTING, AND PARTICIPANTS: It is a prospective, randomized controlled study conducted between July 2020 and January 2023 at the University hospital. N = 96 eligible patients with CgH were selected based on selection criteria and they were divided into cervical spine manipulation (CSM; n = 32), thoracic spine manipulation (TSM; n = 32) and conventional physiotherapy (CPT; n = 32) groups, and received the respective treatment for four weeks. Primary (CgH frequency) and secondary CgH pain intensity, CgH disability, neck pain frequency, neck pain intensity, neck pain threshold, cervical flexion rotation test (CFRT), neck disability index (NDI) and quality of life (QoL) scores were measured. The effects of treatment at various intervals were analyzed using a 3 × 4 linear mixed model analysis (LMM), with treatment group (cervical spine manipulation, thoracic spine manipulation, and conventional physiotherapy) and time intervals (baseline, 4 weeks, 8 weeks, and 6 months), and the statistical significance level was set at P < 0.05. RESULTS: The reports of the CSM, TSM and CPT groups were compared between the groups. Four weeks following treatment CSM group showed more significant changes in primary (CgH frequency) and secondary (CgH pain intensity, CgH disability, neck pain frequency, pain intensity, pain threshold, CFRT, NDI and QoL) than the TSM and CPT groups (p = 0.001). The same gradual improvement was seen in the CSM group when compared to TSM and CPT groups (p = 0.001) in the above variables at 8 weeks and 6 months follow-up. CONCLUSION: The reports of the current randomized clinical study found that CSM resulted in significantly better improvements in pain parameters (intensity, frequency and threshold) functional disability and quality of life in patients with CgH than thoracic spine manipulation and conventional physiotherapy. TRIAL REGISTRATION: Clinical trial registration: CTRI/2020/06/026092 trial was registered prospectively on 24/06/2020.

Additional Effect of Extracorporeal Shockwave Therapy with Lidocaine Injection on Clinical and MRI Findings in Frozen Shoulder: A Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial.

INTRODUCTION: Frozen shoulder is a very common musculoskeletal condition and the evidence related to the additional effects of extracorporeal shockwave therapy (ESWT) with intra-articular (IA) lidocaine injection in individuals with frozen shoulder is rare. Therefore, this study aims to compare and investigate the additional effects of extracorporeal shockwave therapy (ESWT) with intra-articular (IA) lidocaine injection in a frozen shoulder. METHODS: Sixty eligible participants with frozen shoulder were included and the active group (n = 30, age 52.12 ± 5.2 years) received a lidocaine injection (1% lidocaine (Xylocaine) and 2cc (80 mg) methylprednisolone acetate) with active ESWT (3.5 bar air pressure and 2000 pulses with an energy flux density (EFD) » 0.16 mJ/mm2) three sessions a week for 4 weeks. The placebo group (n = 30, age 53.56 ± 5.5 years) received lidocaine injection with placebo treatment (a special head that blocked the shock waves) three sessions a week for 4 weeks. Both groups received progressive resistance exercises (PRE) to the shoulder muscles. The primary outcome was pain intensity, measured with the visual analogue scale. The other outcome measures were the thickness of the coracohumeral ligament (CHL) measured by magnetic resonance imaging (MRI), abduction, and lateral rotation range of motion (ROM), functional disability, kinesiophobia, depression status, and quality of life. Participants were assessed at baseline, after 4 weeks, 8 weeks, and at 6-month follow-up. RESULTS: The post-intervention at 4 weeks showed an improvement of 2.0 (CI 95% 1.71-2.28) in the active group compared to the placebo group. Similar effects were noted after 8 weeks (2.2) (CI 95% 1.91-2.48) and at the 6-month (1.9) (CI 95% 1.61-2.18) follow-up. Similar improvements were also found in the thickness of the CHL ligament (0.6) (CI 95% 0.46-0.73), abduction and lateral rotation (ROM) (- 23.6) (CI 95% - 27.47 to -19.72), (- 18.10) (CI 95% - 19.72 to - 16.47), functional disability (16.2) (CI 95% 14.85-17.54), kinesiophobia (11.0 (CI 95% 10.21-11.98), depression status (4.4) (CI 95% 4.03-4.76) and quality of life (0.9) (CI 95% 0.79-1.00) (p = 0.001) at the 6-month follow-up period, where mean estimates and their confidence intervals all included worthwhile effects. There were no adverse reactions or side effects noted in either the active or placebo groups during and after the treatment. CONCLUSIONS: The study concluded that the addition of extracorporeal shockwave therapy after intra-articular lidocaine injection improves pain, functional disability, range of motion, kinesiophobia, depression status, and quality of life in people with frozen shoulder. TRIAL REGISTRATION: https://ctri.nic.in , identifier; CTRI/2020/04/024834 prospectively registered on 24/04/2020.

Okra [Abelmoschus esculentus (L.) Moench] improved blood glucose and restored histopathological alterations in splenic tissues in a rat model with streptozotocin-induced type 1 diabetes through CD8+ T cells and NF-kß expression.

Diabetes mellitus is a complex metabolic syndrome that involves dysfunction of spleen and other lymphoid organs. Medicinal plants, including okra (Abelmoschus esculentus (L.) Moench), were used widely for diabetes treatment. Scarce data are available about the potential anti-diabetic effects of okra, the histopathological alterations in splenic tissues and the mechanistic pathways underlying this association. The current research investigated the effects of okra pod extract on the biochemical parameters and expression of CD8+ T cells and nuclear factor kappa (NF-k) B and releasing proinflammatory cytokines in spleen in streptozotocin (STZ)-induced diabetic rat models. A total of 50 mature male Wister albino rats were divided into five isolated groups; the first served as control (untreated) animals, the second (DM group) diabetes induced by STZ (at a dose of 45 mg/kg body weight, administered intraperitoneally), the third group (DM + Insulin): diabetic rats administered insulin subcutaneously (10 units/kg bw/day) daily for 4 weeks, the fourth group was administrated 400 mg/kg okra extract daily for 4 weeks, and diabetic induced rats in the fifth group were administrated 400 mg/kg okra extract daily for 4 weeks. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity in Abelmoschus esculentus (L.) Moench was studied, and the content of phenolic compounds in okra pods was estimated using high-performance liquid chromatography. Diabetes induction led to decreased body weight, increased blood glucose levels. Capsular thickness was significantly increased, white pulp was widely dispersed, and mature lymphocytes in the periphery were also drastically decreased, with thick follicular arteries, necrosis, and depletion of lymphocytes in the germinal center. Red pulp revealed severe congestion and degenerative changes, deposition of hemosiderin granules and lymphocytic depletion. In addition, collagen fiber deposition was increased also in this group. The induction of diabetes exaggerated NF-kß expression and mediated downregulation of the expression of CD8+ T cells in spleen tissue. Interestingly, oral administration of okra extracts post diabetes induction could mitigate and reverse such adverse effects. Altogether, our study points out the potential benefits of okra in improving blood glucose levels and restoring histopathological alterations in splenic tissues through CD8+ T cells and NF-kß expression in a diabetic rat model.

Modulation of inflammatory, oxidative, and apoptotic stresses mediates the renoprotective effect of daidzein against glycerol-induced acute kidney injury in rats.

Acute kidney injury (AKI) is a life-threatening complication that accompanies rhabdomyolysis. Daidzein is a dietary isoflavone that has various biological activities. This study examined the therapeutic potential of daidzein and the underlying mechanisms against AKI induced by glycerol in male rats. Animals were injected once with glycerol (50%, 10 ml/kg, intramuscular) for induction of AKI and pre-treated orally with daidzein (25, 50, and 100 mg/kg) for 2 weeks. Biochemical, histopathological, immunohistopathological, and molecular parameters were assessed to evaluate the effect of daidzein. The results revealed that the model group displayed remarkable functional, molecular, and structural changes in the kidney. However, pre-administration of daidzein markedly decreased the kidney relative weight as well as the levels of urea, creatinine, K, P, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C. Further, daidzein lessened the rhabdomyolysis-related markers [lactate dehydrogenase (LDH) and creatine kinase (CK)]. Notably, the enhancement of the antioxidant biomarkers [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and reduced glutathione (GSH) is accompanied by a decrease in malondialdehyde (MDA) and nitric oxide (NO) levels. Moreover, upregulated gene expression levels of nuclear factor erythroid 2-related factor 2 (Nfe212) and hemeoxygenase-1 (Hmox1) were exerted by daidzein administration. Rats who received daidzein displayed markedly lower interleukin-1ß (IL-1ß), tumor nuclear factor-α (TNF-α), myleoperoxidase (MPO), and nuclear factor kappa B (NF-κB) levels together with higher interleukin-10 (IL-10) related to the model group. Remarkably, significant declines were noticed in the pro-apoptotic (Bax and caspase-3) and rises in antiapoptotic (Bcl-2) levels in the group that received daidzein. The renal histological screening validated the aforementioned biochemical and molecular alterations. Our findings support daidzein as a potential therapeutic approach against AKI-induced renal injury via suppression of muscle degradation, oxidative damage, cytokine release, and apoptosis.

Thyroid Cancer Knowledge and Awareness in Saudi Arabia: A Cross-Sectional Study.

Background Thyroid cancer incidence has been increasing worldwide over the last few decades. It is the most common endocrine cancer and is most common among females. The study contributes to filling the knowledge gap among Saudi people regarding thyroid cancer. Objectives This research aims to investigate the level of thyroid cancer knowledge and awareness in Saudi Arabia, identify potential knowledge gaps, and develop targeted strategies for enhancing public awareness and education. Methods A cross-sectional, voluntary online survey was conducted from 1st August 2023 to 1st October 2023 among residents living in Saudi Arabia over 18 years of age. The participants included were 2030 respondents. Data analysis was performed using RStudio (R version 4.3.0; R Foundation for Statistical Computing, Vienna, Austria). Results Among the participants, the majority were female (60.4%). A total of 49.7% of the individuals reported having a moderate to high level of knowledge about thyroid cancer. While 63.9% knew the association of a lump in the neck to thyroid cancer, 82.6% affirmed to consult a doctor upon discovering a lump, 72.1% knew that regular monitoring of neck lumps is crucial for early diagnosis and treatment of precancerous conditions, 38.7% were aware of females being prone to thyroid cancer, and 59.2% were aware of the link between lifestyle and increased risk. Higher awareness scores were positively associated with female gender, previously having thyroid function tests done, and previously undergoing a US scan of the thyroid. Conclusion In this study, Saudi individuals are reported to lack some aspects of knowledge and perception of thyroid cancer. This study emphasizes filling the existing knowledge gap in thyroid cancer awareness in the Saudi population.

Novel Insights about Synergistic Effect of Zamzam Water with SGL2 Inhibitors on Wound Healing in STZ-Induced Diabetic Rats: The Role of anti-Inflammatory and Proangiogenic Effects.

Background: Hyperglycemia usually impairs wound healing by dysregulating the inflammatory response and angiogenesis. This study aimed to examine the synergistic effect of dapagliflozin and Zamzam water (ZW) on the healing of diabetic wounds and to explore their anti-inflammatory and proangiogenic effects.Materials and methods: A full-thickness excisional wound was made on the backs of all groups after two weeks of diabetes induction. Forty rats were divided into five groups, with eight rats per group; Group 1: Control non-diabetic rats; Group II: Untreated diabetic rats; Group III: Diabetic rats drinking ZW; Group IV: Diabetic rats receiving an oral dose of 1 mg/kg dapagliflozin; and Group V: Received both dapagliflozin and ZW. The healing of diabetic wounds was assessed by measuring wound closure, oxidative stress markers, immunohistochemical staining of NF-ßB, VEGF, CD34, CD45, Ki-67, and eNOS, gene expression of MMP-9, TGF-ß1, EGF-b1, FGF, and Col1A1, protein levels of TNFα, IL-1ß, IL6, Ang II, and HIF-1α by ELISA assay, and histological examination with H & E and Masson's trichrome. Combined treatment with dapagliflozin and ZW significantly (p < 0.05) enhanced the wound closure and antioxidant enzyme level, with apparent histological improvement, and shortened the inflammatory stage of the diabetic wound by decreasing the level of inflammatory markers NF-κB, TNF-α, IL-1ß, IL6, and CD45. Therefore, it improved angiogenesis markers VEGF, CD34, eNOS, EGF-ß1, FGF, Ang II, and HIF-1α, increasing Ki-67 cellular proliferation. Moreover, it enhanced the remodeling stage by increasing MMP-2, TGF-ß1, and Col1A1 levels compared to diabetic rats.

Melatonin downregulates the increased hepatic alpha-fetoprotein expression and restores pancreatic beta cells in a streptozotocin-induced diabetic rat model: a clinical, biochemical, immunohistochemical, and descriptive histopathological study.

Background: Diabetes mellitus (DM) is a chronic metabolic disorder. Hepatopathy is one of the serious effects of DM Melatonin (MT) is a potent endogenous antioxidant that can control insulin output. However, little information is available about the potential association between melatonin and hepatic alpha-fetoprotein expression in diabetes. Objective: This study was conducted to assess the influence of MT on diabetes-related hepatic injuries and to determine how ß-cells of the pancreas in diabetic rats respond to MT administration. Materials and methods: Forty rats were assigned to four groups at random (ten animals per group). Group I served as a normal control group. Group II was induced with DM, and a single dose of freshly prepared streptozotocin (45 mg/kg body weight) was intraperitoneally injected. In Group III, rats received 10 mg/kg/day of intraperitoneal melatonin (IP MT) intraperitoneally over a period of 4 weeks. In Group IV (DM + MT), following the induction of diabetes, rats received MT (the same as in Group III). Fasting blood sugar, glycosylated hemoglobin (HbA1c), and serum insulin levels were assessed at the end of the experimental period. Serum liver function tests were performed. The pancreas and liver were examined histopathologically and immunohistochemically for insulin and alpha-fetoprotein (AFP) antibodies, respectively. Results: MT was found to significantly modulate the raised blood glucose, HbA1c, and insulin levels induced by diabetes, as well as the decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, MT attenuated diabetic degenerative changes in the pancreas and the hepatic histological structure, increased the ß-cell percentage area, and decreased AFP expression in the liver tissue. It attenuated diabetes-induced hepatic injury by restoring pancreatic ß-cells; its antioxidant effect also reduced hepatocyte injury. Conclusion: Collectively, the present study confirmed the potential benefits of MT in downregulating the increased hepatic alpha-fetoprotein expression and in restoring pancreatic ß-cells in a streptozotocin-induced diabetic rat model, suggesting its promising role in the treatment of diabetes.

Corrigendum: Melatonin ameliorates serobiochemical alterations and restores the cardio-nephro diabetic vascular and cellular alterations in streptozotocin-induced diabetic rats.

[This corrects the article DOI: 10.3389/fvets.2023.1089733.].

Role of virtual reality distraction technique to improve chest burns with acute respiratory distress syndrome (ARDS) following smoke inhalation in middle-aged adults - A randomized controlled study.

BACKGROUND: Burns of the chest region constitute a common burn and develops skin contractures around the thorax region. Inhalation of toxic gases and chemical irritants during the fire leads to Acute Respiratory Distress Syndrome (ARDS). Breathing exercises are painful but are needed to help counteract contractures and increase lung capacity. These patients are usually in pain and extremely anxious about chest physiotherapy. Virtual reality distraction is one such technique that is gaining immense popularity when compared to other pain distraction techniques. However, studies examining the efficacy of the virtual reality distraction technique in this population are lacking. OBJECTIVES: To find and compare the effects of the virtual reality distraction technique as a pain alleviation tool for reducing pain during chest physiotherapy in chest burns patients with ARDS in middle-aged adults. METHODS: A randomized controlled study was conducted at the physiotherapy department between 1st Sep 2020 and 30th Dec 2022. The eligible sixty subjects were randomized into two groups: The virtual reality distraction group (n = 30) received virtual reality distraction technique and the control group (n = 30) received progressive relaxation technique before chest physiotherapy as a pain distraction technique. All the participants received chest physiotherapy as a common treatment (treatment as usual). Primary (Visual Analogue Scale - VAS) and secondary (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, peak expiratory flow (PEF), residual volume (RV), functional residual capacity (FRC), total lung capacity (TLC), RV/TLC, and diffusing capacity for carbon monoxide of the lungs (DLCO) outcome measures were measured at baseline, after four weeks, eight weeks and at six months follow up. The effects between the two groups were analyzed using the independent t-test and chi-square test. The intra-group effect was analyzed with a repeated measure ANOVA test. RESULTS: Baseline demographic characters and study variables show homogenous distribution between the groups (p > 0.05). Four weeks following two different training protocols virtual reality distraction group shows more significant changes in pain intensity, FVC, FEV1, FEV1/FVC, PEF, RV, FRC, TLC, RV/TLC, and DLCO (p = 0.001) but not in RV (p = 0.541). The similar improvements were noted in the 8 weeks and 6 months follow up. CONCLUSION: The reports of the study concluded that virtual reality distraction is an effective and useful technique in reducing pain and increasing lung capacity in chest burn patient with ARDS following smoke inhalation in community-dwelling middle-aged adults. In the virtual reality distraction group, the patients reported significantly less pain and clinically meaningful changes in pulmonary functions as compared to the control group (physiotherapy + relaxation).

Knowledge and Practice of the Preventive and Care Methods for Diabetic Foot Among the Caregivers of Diabetic Patients in Saudi Arabia.

Background Diabetic foot syndrome is a complex and multifactorial disease process involving neuropathy, peripheral arterial disease, osteomyelitis, diabetic foot ulcer (DFU), and amputation. DFUs are a common and burdensome manifestation of the syndrome, responsible for diabetes-related morbidity and mortality. Successful management of DFU requires collaboration between patients and caregivers. This study assesses the knowledge, experience, and practices of the caregivers of diabetic foot patients in Saudi Arabia, highlighting the need for targeted interventions to improve knowledge and practices in certain subgroups of caregivers. Method The primary objective of this study was to evaluate the proficiency and practicality of caregivers who provide care to patients with diabetic foot in the Kingdom of Saudi Arabia. To accomplish this, a cross-sectional study was conducted among caregivers of diabetic foot patients who were aged 18 years or older and living in Saudi Arabia. The participants were randomly chosen to ensure that the sample was representative. The data collection process involved the distribution of a structured online questionnaire via various social media platforms. Prior to the distribution of the questionnaire, the participants were informed about the study's objectives, and their informed consent was obtained. Additionally, adequate measures were taken to ensure the confidentiality of the participants and their caregiving status. Results Among the initial pool of 2990 participants, 1023 individuals were excluded from the study due to their status as non-caregivers of diabetic patients or being under the age of 18 years. Consequently, the final sample size consisted of 1921 caregivers. The majority of the participants were female (61.6%), married (58.6%), and had a bachelor's degree (52.4%). The findings revealed that 34.6% of caregivers were attending to patients with diabetic foot, of which 8.5% reported poor foot status and 9.1% reported amputation. Caregivers reported examining the patient's feet in 75.2% of cases, and the feet were cleaned and moisturized by either the patient or caregiver. Nails were trimmed by 77.8% of caregivers, and 49.8% of them did not permit patients to walk barefoot. Moreover, knowledge of diabetic foot care was positively correlated with being female, having a post-graduate degree, having personal experience with diabetes, caring for a patient with diabetic foot, and having prior experience in treating diabetic foot. Conversely, lower knowledge levels were associated with divorced or unemployed caregivers and those residing in the northern region. Conclusion The present study highlights that caregivers of diabetic foot patients in Saudi Arabia possess a satisfactory level of knowledge and follow appropriate practices regarding foot care. Nonetheless, it is imperative to identify specific subgroups of caregivers who may require additional education and training to improve their knowledge and practices concerning diabetic foot care. The results of this study could potentially inform the design of tailored interventions aimed at reducing the significant burden of morbidity and mortality attributed to diabetic foot syndrome in the Saudi Arabian context.

Melatonin ameliorates serobiochemical alterations and restores the cardio-nephro diabetic vascular and cellular alterations in streptozotocin-induced diabetic rats.

Melatonin possesses a wide range of pharmacological activities, including antidiabetic properties. Diabetes mellitus (DM) induces several physiopathological changes in body organs, which could be observed lately after systemic failure. In the current study, we aimed to investigate the serobiochemical changes and the histopathological picture in the diabetic heart and the kidney early before chronic complications and highlight the association between hyperglycemia, glomerular alterations, and cardiovascular changes. In addition, the role of melatonin in the treatment of cardio-nephro diabetic vascular and cellular adverse changes in streptozotocin-induced diabetic rats was also studied. A total of 40 mature Wistar albino rats were distributed into five groups; (1) control untreated rats, (2) diabetic mellitus untreated (DM) rats, in which DM was induced by the injection of streptozotocin (STZ), (3) control melatonin-treated (MLT), (4) melatonin-treated diabetic (DM + MLT) rats, in which melatonin was injected (10 mg/kg/day, i.p.) for 4 weeks, and (5) insulin-treated diabetic (DM + INS) rats. The serum biochemical analysis of diabetic STZ rats showed a significant (P < 0.05) increase in the concentrations of blood glucose, total oxidative capacity (TOC), CK-MB, endothelin-1, myoglobin, H-FABP, ALT, AST, urea, and creatinine as compared to control rats. In contrast, there was a significant (P < 0.05) decrease in serum concentration of insulin, total antioxidative capacity (TAC), total nitric oxide (TNO), and total protein level in DM rats vs. the control rats. Significant improvement in the serobiochemical parameters was noticed in both (DM + MLT) and (DM + INS) groups as compared with (DM) rats. The histological examination of the DM group revealed a disorder of myofibers, cardiomyocyte nuclei, and an increase in connective tissue deposits in between cardiac tissues. Severe congestion and dilation of blood capillaries between cardiac muscle fibers were also observed. The nephropathic changes in DM rats revealed various deteriorations in glomeruli and renal tubular cells of the same group. In addition, vascular alterations in the arcuate artery at the corticomedullary junction and interstitial congestion take place. Melatonin administration repaired all these histopathological alterations to near-control levels. The study concluded that melatonin could be an effective therapeutic molecule for restoring serobiochemical and tissue histopathological alterations during diabetes mellitus.

Silver Nanoparticles Enhance Oxidative Stress, Inflammation, and Apoptosis in Liver and Kidney Tissues: Potential Protective Role of Thymoquinone.

Silver nanoparticles (AgNPs) are the most common nanomaterials in consumer products. Therefore, it has been crucial to control AgNPs toxicological effects to improve their safety and increase the outcome of their applications. This work investigated the possible protective effect of thymoquinone (TQ) against AgNPs-induced hepatic and renal cytotoxicity in rats. Serum markers of liver and kidney functions as well as liver and kidney oxidative stress status, pro-inflammatory cytokines, apoptosis markers, and histopathology were assessed. TQ reversed AgNPs-induced elevation in serum liver and kidney function markers, including aspartate transaminase, alanine transaminase, urea, and creatinine. Moreover, TQ co-administration with AgNPs alleviates hepatic and renal oxidative insults by decreasing MDA and NO levels with a significant increase in the activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione recycling enzymes peroxidase and reductase) compared to AgNPs-treated rats. Besides, TQ upregulated hepatic and renal Nrf2 gene expression in AgNPs-intoxicated rats. Furthermore, TQ co-administration decreased the hepatic and renal pro-inflammatory mediators represented by IL-1ß, TNF-α, TGF-ß, and NF-κB levels. Besides, TQ co-administration decreased apoptotic protein (Bax) levels and increased the anti-apoptotic protein (Bcl-2) levels. These findings were confirmed by the histopathological examination of hepatic and renal tissues. Our data affirmed the protective effect of TQ against AgNPs cytotoxicity and proposed a possible mechanism of TQ antioxidant, anti-inflammatory, and anti-apoptotic effects. Consequently, we could conclude that using TQ might control AgNPs toxicological effects, improve their safety, and increase the outcome of their applications.

Therapeutic antischizophrenic activity of prodigiosin and selenium co-supplementation against amphetamine hydrochloride-induced behavioural changes and oxidative, inflammatory, and apoptotic challenges in rats.

Schizophrenia (SCZ), a multifactorial neuropsychiatric disorder, is treated with inefficient antipsychotics and linked to poor treatment outcomes. This study, therefore, investigated the combined administration of prodigiosin (PDG) and selenium (Na2SeO3) against SCZ induced by amphetamine (AMPH) in rats. Animals were allocated into four groups corresponding to their respective 7-day treatments: control, AMPH (2 mg/kg), PDG (300 mg/kg) + Na2SeO3 (2 mg/kg), and AMPH + PDG + Na2SeO3. The model group exhibited biochemical, molecular, and histopathological changes similar to those of the SCZ group. Contrastingly, co-administration of PDG and Na2SeO3 significantly increased the time for social interaction and decreased AChE and dopamine. It also downregulated the gene expression of NMDAR1 and restored neurotrophin (BDNF and NGF) levels. Further, PDG combined with Na2SeO3 improved the antioxidant defence of the hippocampus by boosting the activities of SOD, CAT, GPx, and GR. These findings were accompanied by an increased GSH, alongside decreased MDA and NO levels. Furthermore, schizophrenic rats having received PDG and Na2SeO3 displayed markedly lower IL-1ß and TNF-α levels compared to the model group. Interestingly, remarkable declines in the Bax (pro-apoptotic) and increases in Bcl-2 (anti-apoptotic) levels were observed in the SCZ group that received PDG and Na2SeO3. The hippocampal histological examination confirmed these changes. Collectively, these findings show that the co-administration of PDG and Na2SeO3 may have a promising therapeutic effect for SCZ. This is mediated by mechanisms related to the modulation of cholinergic, dopaminergic, and glutaric neurotransmission and neurotrophic factors, alongside the suppression of oxidative damage, neuroinflammation, and apoptosis machinery.

Protocatechuic acid counteracts oxidative stress and inflammation in carrageenan-induced paw edema in mice.

Protocatechuic acid (PCA), a phenolic compound found in teas, fruits, and vegetables, is widely recognized with its antioxidant and anti-inflammatory activities. Here, we verified the protective role of PCA on carrageenan (CGN)-induced paw edema in mice. Forty-five male Swiss albino mice were assigned into five groups: control group, CGN-injected group (1% w/v), PCA (25 mg/kg) + CGN group. PCA (50 mg/kg) + CGN group and diclofenac sodium (20 mg/kg) + CGN group. PCA and diclofenac sodium were administered orally for 5 consecutive days prior to the CGN injection. PCA pretreatment notably decreased the volume of the developed edema and alleviated the histopathological alterations induced by carrageenan. Additionally, PCA administration enhanced the cellular antioxidant capacity as demonstrated by the increased levels of catalase, superoxide dismutase, and reduced glutathione, in addition to the decreased malondialdehyde level in the edematous tissue. Interestingly, PCA administration was able significantly to suppress the developed inflammatory response upon carrageenan injection as indicated by the decreased levels and expression of pro-inflammatory cytokines and mediators including tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, inducible nitric oxide synthase, nitric oxide, cyclooxygenase-II, prostaglandin E2, monocyte chemoattractant protein-1, myeloperoxidase and nuclear factor kappa B. These results collectively confirm the protective effect of PCA against carrageenan-induced paw edema owing to its antioxidant and anti-inflammatory characteristics.

Possible Role of Kaempferol in Reversing Oxidative Damage, Inflammation, and Apoptosis-Mediated Cortical Injury Following Cadmium Exposure.

Cadmium (Cd) is a heavy metal of considerable toxicity, inducing a number of hazardous effects to humans and animals including neurotoxicity. This experiment was aimed to investigate the potential effect of kaempferol (KPF) against Cd-induced cortical injury. Thirty-two adult Sprague-Dawley rats were divided equally into four groups. The control rats intraperitoneally (i.p.) injected with physiological saline (0.9% NaCl), the cadmium chloride (CdCl2)-treated rats were i.p. injected with 4.5 mg/kg of CdCl2, the KPF-treated rats were orally gavaged with 50 mg/kg of KPF, and the KPF + CdCl2-treated rats were administered orally 50 mg/kg of KPF 120 min before receiving i.p. injection of 4.5 mg/kg CdCl2. CdCl2 exposure for 30 days led to the accumulation of Cd in the cortical tissue, accompanied by a reduction in the content of monoamines and acetylcholinesterase activity. Additionally, CdCl2 induced a state of oxidative stress as evidenced by the elevation of lipid peroxidation and nitrate/nitrite levels, while glutathione content and the activities of glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase were decreased. Moreover, CdCl2 mediated inflammatory events in the cortical tissue through increasing tumor necrosis factor-alpha and interleukin-1 beta levels and upregulating the expression of inducible nitric oxide synthase. Furthermore, pro-apoptotic proteins (Bax and caspase-3) were elevated, while Bcl-2, the anti-apoptotic protein, was decreased. Also, histological alterations were observed obviously following CdCl2. However, KPF pretreatment restored significantly the examined markers to be near the normal values. Hence, the obtained data provide evidences that KPF pretreatment has the protective effect to preserve the cortical tissues in CdCl2-exposed rats by restraining oxidative stress, inflammatory response, apoptosis, neurochemical modulation, and improving the histological changes.

Neuromodulatory effects of green coffee bean extract against brain damage in male albino rats with experimentally induced diabetes.

Diabetes mellitus is an increasing metabolic disease worldwide associated with central nervous system disorders. Coffee is a widely consumed beverage that enriched with antioxidants with numerous medicinal applications. Accordingly, the present study aimed to investigate the therapeutic potential of orally administered green coffee bean water extract (GCBWE) against cortical damage induced by high fat diet (HFD) followed by a single injection of streptozotocin (STZ) in rats. Metformin (Met) was used as standard antidiabetic drug. Animals were allocated into six groups: control, GCBWE (100 mg/kg), HFD/STZ (40 mg/kg), HFD/STZ + GCBWE (50 mg/kg), HFD/STZ + GCBWE (100 mg/kg) and HFD/STZ + Met (200 mg/kg) which were treated daily for 28 days. Compared to control rats, HFD/STZ-treated rats showed decreased levels of cortical dopamine, norepinephrine and serotonin with marked increases in their metabolites. Further, HFD/STZ treatment resulted in notable elevations in malondialdehyde, protein carbonyl and total nitrite levels paralleled with declines in antioxidant markers (SOD, CAT, GPx, GR and GSH) and down-regulations of Sod2, Cat, GPx1 and Gsr gene expression. Neuroinflammation was evident in diabetic animals by marked elevations in TNF-α, IL-1ß and up-regulation of inducible nitric oxide synthase. Significant rises incaspase-3 and Bax with decline in Bcl-2 level were noticed in diabetic rats together with similar results in their gene expressions. Cortical histopathological examination supported the biochemical and molecular findings. GCBWE administration achieved noteworthy neuroprotection in diabetic animals in most assessed parameters. The overall results suggested that antioxidant, anti-inflammatory; anti-apoptotic activities of GCBWE restored the cortical neurochemistry in diabetic rats.

Luteolin protects against lead acetate-induced nephrotoxicity through antioxidant, anti-inflammatory, anti-apoptotic, and Nrf2/HO-1 signaling pathways.

Lead (Pb) is one of the most common heavy metal pollutants affecting living organisms. It induces nephrotoxicity with significant alterations in renal structure and function. Luteolin (LUT) a flavonoid present in various plant products is well known for exhibiting numerous pharmacological properties. We evaluated the protective efficacy of LUT against Pb-induced renal injury in male Wistar rats. Four experimental groups: control, LUT (50 mg/kg, orally), PbAc (20 mg/kg, i.p.), LUT + PbAc (at the aforementioned doses) were maintained for 7 days. PbAc administration significantly increased renal Pb accumulation, urea, and creatinine levels in serum, and induced renal histological alterations. Additionally, compared to the control rats, PbAc-treated rats exhibited significantly low levels of antioxidant enzyme activity and expression (SOD, CAT, GPx and GR), as well as high MDA levels. Moreover, PbAc exposure downregulated Nfe212 and Homx1 mRNA expression and significantly increased inflammatory marker (TNF-α, IL-1ß and NO) levels in renal tissue. PbAc significantly upregulated the synthesis of apoptotic related proteins and downregulated antiapoptotic protein expression. Notably, LUT pretreatment of PbAc-treated rats provided significant nephroprotection and reversed the alterations in the abovementioned parameters. In conclusion, LUT provided significant protection against PbAc intoxication via antioxidant, anti-inflammatory, and anti-apoptotic activities by activating the Nrf2/ARE signaling pathway.