Adverse hematological profiles associated with chlorpromazine antipsychotic treatment in male rats: Preventive and reversal mechanisms of taurine and coenzyme-Q10.

Chlorpromazine (CPZ) is one of the most effective antipsychotic drugs used for managing psychotic related disorders owing to its dopamine receptor blocking action. However, pharmacological investigations against CPZ's cytotoxic effect have remained scarce. Hence, this study investigated the preventive and reversal effects of taurine and coenzyme-Q10 (COQ-10), which are compounds with proven natural antioxidant properties, against CPZ-induced hematological impairments in male rats. In the preventive study, rats received oral saline (10 ml/kg), taurine (150 mg/kg/day), COQ-10 (10 mg/kg/day) or in combination for 56 days, alongside CPZ (30 mg/kg, p.o.) between days 29-56. In the reversal protocol, rats had CPZ repeatedly for 56 days before taurine and COQ-10 treatments or their combination from days 29-56. Rats were also given taurine (150 mg/kg/day), and COQ-10 (10 mg/kg/day) alone for 56 days. Serums were extracted and assayed for hematological, with oxidative and inflammatory markers. CPZ induced decreased red/white blood cells, erythropoietin, platelet count, packed cell volume and hemoglobin, neutrophil, and lymphocyte, which were prevented and reversed by taurine and COQ-10, or their combination. Taurine and COQ-10 improved mean corpuscular volume, hemoglobin concentration, with increased erythropoietin levels relative to CPZ groups. CPZ-induced increased malondialdehyde, tumor necrosis factor-alpha and interleukin-6 levels with decreased interleukin-10, glutathione, and superoxide-dismutase were prevented and reversed by taurine and COQ-10 in comparison with CPZ groups. Taurine and COQ-10 alone notably improved the antioxidant/anti-inflammatory status relative to controls. Among other mechanisms, taurine and COQ-10 abated CPZ-induced hematological deficiencies, via decreased serum levels of oxidative stress, and pro-inflammatory cytokines release, with increased antioxidants and anti-inflammation function.

Ginkgo biloba modulates ET-I/NO signalling in Lead Acetate induced rat model of endothelial dysfunction: Involvement of oxido-inflammatory mediators.

This study investigated the modulatory effect of Ginkgo biloba extract on lead acetate-induced endothelial dysfunction. Animals were administered GBE (50 mg/kg and 100 mg/kg orally) after exposures to lead acetate (25 mg/kg orally) for 14 days. Aorta was harvested after euthanasia, the tissue was homogenised, and supernatants were decanted after centrifuging. Oxidative, nitrergic, inflammatory, and anti-apoptotic markers were assayed using standard biochemical procedure, ELISA, and immunohistochemistry, respectively. GBE reduced lead-induced oxidative stress by increasing SOD, GSH, and CAT as well as reducing MDA levels in endothelium. Pro-inflammatory cytokines (TNF-α and IL-6) were reduced while increasing Bcl-2 protein expression. GBE lowered endothelin-I and raised nitrite levels. Histological changes caused by lead acetate were normalised by GBE. Our findings suggest that Ginkgo biloba extract restored endothelin-I and nitric oxide functions by increasing Bcl-2 protein expression and reducing oxido-inflammatory stress in endothelium.

Comparative Analysis of Fasting Blood Glucose and Salivary Electrolytes Concentrations among Individuals with Type II Diabetes: A Randomized Controlled Hospital Based Study.

Salivary gland dysfunction is common in people with diabetes. This study aimed to compare the measurements of salivary electrolytes (SE); Na+, K+, Cl- and HCO3 - between diabetes and an age matched control group, and assess the relationship between fasting blood glucose (FBG) and salivary electrolytes, and salivary glucose (SG). Eighty-five human participants [diabetes group, n = 45 (23 males and 22 females) and control group, n = 40 (20 males and 20 females)] aged between 25 and 65years were tested. Saliva samples were taken between 7.00 am and 8.00 am after an overnight fast and SG and SE concentrations were analysed. Diabetes mellitus was defined using FBG ≥ 126 mg/dl. SG and SE concentrations were analysed using t-test and Pearson Correlation Coefficient tested the relationship between FBG and Salivary electrolytes and glucose. The participants were matched in their baseline demographic characteristics with a mean age of 49 years (standard deviation SD, 11 years), body mass index (25.7 kg/m2 (SD, 3.6). Half of them were males (50.6 %) and predominantly traders (30.6 %). However, the mean values for the salivary sodium, potassium, chloride and bicarbonate electrolytes were significantly higher in the diabetes group compared with the control group (P < 0.05). Of the salivary electrolytes, only the bicarbonate was significantly correlated with FBG (r = -0.594, p = 0.004) in female participants. This study found that people with diabetes have elevated salivary electrolytes which were not dependent on their age and gender. Although this study suggests some potential for saliva as an alternative in monitoring of diabetes mellitus, extensive research is required before we can reach any firm conclusion.

Proinflammatory and Anti-inflammatory Cytokine Response to Isometric Handgrip Exercise and the Effects of Duration and Intensity of the Isometric Efforts in Prehypertensive Participants.

Objective: The purpose of this study was to investigate the responses of selected inflammatory cytokines to isometric handgrip exercise and identify possible effects of intensity and duration of the isometric effort on these variables. Methods: A total of 192 sedentary prehypertensive Nigerian participants aged between 30 and 50 years were recruited into the study and randomly distributed into 3 groups of 64 participants each. The participants performed 24 consecutive days of isometric handgrip exercise at 30% maximum voluntary contraction. At the end of the 24 days, group 1 discontinued the exercise protocol, while group 2 continued the exercise protocol for another 24 consecutive days, and group 3 continued with the exercise protocol for another 24 consecutive days but at 50% maximum voluntary contraction. The parameters used to assess the inflammatory cytokine variables included interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-α). Results: There was an increase in the resting values of IL-10 across the 3 groups, while the resting values of IL-6 and TNF-α were reduced significantly across groups. Generally, the exercise-induced changes in the levels of these cytokines (TNF-α, IL-6, and IL-10) should improve inflammatory and metabolic abnormalities. Conclusion: The isometric handgrip exercise protocols in this study resulted in elevation of anti-inflammatory cytokine (IL-10) and reductions in the values of proinflammatory cytokines TNF- α and IL-6.

Therapeutic efficacy of N-acetylcysteine and zinc sulphate against di-(2-ethylhexyl) phthalate-induced testicular oxido-nitrergic stress in male Wistar rat.

The therapeutic efficacy of N-acetylcysteine (NAC) and zinc sulphate on di-(2-ethylhexyl) phthalate (DEHP)-induced testicular oxido-nitrergic stress in rats was investigated in 36 male Wistar rats (170 ± 10 g) randomly assigned into one of six groups (n = 6). Group 1 (control) received 2.5 ml/kg of distilled water for 42 days, while group 2 (vehicle) received 2.5 ml/kg of corn oil for 42 days. Groups 3,4,5, and 6 were administered DEHP (750 mg/kg/day) for 21 days, after which groups 4, 5, and 6 received zinc sulphate (0.5 mg/kg/day), NAC (100 mg/kg/day), and zinc sulphate (0.5 mg/kg/day) + NAC (100 mg/kg/day) for an additional 21 days respectively. After the experimental period, the animals were euthanized by light thiopental sodium, and their testes were carefully dissected out for histological and biochemical assays. The result shows a significant alteration in testicular levels of malondialdehyde, nitric oxide, antioxidant enzymes, total antioxidant capacity, sulphydryl levels, dehydrogenases and testicular architecture following the administration of DEHP. These effects were reversed by coadministration of NAC and zinc sulphate in the study. We therefore concluded that the combined effects of NAC and ZnSO4 effectively improved testicular antioxidant status and reduced testicular nitregic stress, thus improving testicular architecture and functions.

Up-regulation of B-cell lymphoma factor-2 expression, inhibition of oxidative stress and down-regulation of pro-inflammatory cytokines are involved in the protective effect of cabbage (Brassica oleracea) juice in lead-induced endothelial dysfunction in rats.

BACKGROUND: Oxido-inflammatory stress and dysregulation of nitric oxide (NO) system has been implicated in lead toxicity. Cabbage is an antioxidant-rich household vegetable with plethora of therapeutic potentials. The present study investigated the anti-oxido-inflammatory activity of cabbage in lead-induced endothelial dysfunction. METHODS: Twenty (20) male Wistar rats were selected into four groups (n = 5) and treated with distilled water (1 mL/100 g b.wt), lead acetate (25 mg/kg b.wt), cabbage juice (1 mL/100 g b.wt) and lead acetate (25 mg/kg b.wt) plus cabbage juice (1 mL/100 g b.wt) respectively. Treatment was done orally for 28 days, thereafter, oxidative stress (SOD, CAT, GSH, and MDA), inflammatory (TNF-α and IL-6) and apoptotic (Bcl-2) markers were assayed using standard biochemical assays as well as histoarchitectural study of the endothelium. RESULTS: The results showed that they were significant increase in MDA, ET-1, TNF-α and IL-6 while SOD, GSH, CAT, NO and Bcl-2 protein expression were decreased in Lead exposed animals. Endothelial histoarchitecture was also altered. Following Cabbage juice treatment, MDA, ET-I, TNF-α and IL-6 were down-regulated while SOD, GSH, CAT, NO and Bcl-2 protein expression were up-regulated. Histoarchitecture was significantly recovered. CONCLUSION: The study suggests that cabbage juice could mitigates Lead-induced endothelial dysfunction by modulating oxido-inflammatory and anti-apoptotic mediators. DATA AVAILABILITY: All data are available upon request.

Immune system response to isometric handgrip exercise and effects of duration and intensity of the exercise protocol on selected immune system parameters in prehypertensives.

BACKGROUND: Recent studies have shown that physical exercise significantly modulates immunocyte dynamics and possibly plays a significant role on immune function. This study examined the responses of some selected immune system parameters to isometric handgrip exercise and identified possible effects of intensity and duration of the exercise protocols. METHODS: One hundred and ninety-two (N=192) sedentary pre-hypertensive subjects, aged between 30-50 years were recruited into the study. They were randomly distributed into three groups of 64 subjects each. A detailed explanation and a demonstration of the exercise protocol were given to the subjects and they were asked to report at the Exercise Physiology unit of the Physiotherapy department, Federal Medical Centre, Asaba, Delta State at 4.00 pm daily for the exercise practice. The training session for each day took place between the hours of 4.00 pm and 8.00 pm daily (FMC/ASB/A81.VOL.XII/101). The subjects performed a 24 consecutive day's isometric handgrip exercise at 30% Maximum Voluntary Contraction (MVC). At the end of the 24 days, group one (GP1) discontinued with the exercise protocol, while group two (GP2) and group three (GP3) continued with the exercise protocol for another 24 consecutive days nevertheless GP3 performed at an increased intensity of 50% MVC. The clinical trial was registered with Nigeria Clinical Trial Registry, Federal Ministry of Health, Abuja Nigeriawith Trial No: 1216582 (https://www.nctr.nhrec.net/viewTrials.php?TID=1216582). RESULTS: At the end of the study, the result shows thatthe number of CD4 cells and CD4/CD8 ratio significantly (P<0.05) increased while the CD8 cell decreased in GP2 and GP3. It was further shown that increase in duration produced a more significant change compared to an increase in intensity of the isometric effort. CONCLUSION: The study established that isometric handgrip exercise alters the circulating levels of the immune system parameters which could have positive beneficial effects on the prehypertensive individuals as the number of CD4 cells and CD4/CD8 ratio increased especially when practiced over a longer duration.

In Vivo Attenuation of Alcohol- and Cadmium Chloride-Induced Testicular Toxicity Modulated by Silymarin in Male Wistar Rat.

The aim of the study is to investigate the in vivo attenuation of alcohol- and cadmium chloride-induced testicular toxicity modulated by Silymarin in male Wistar rats. A total of fifty-six (56) Wistar rats were used for this study and they were randomized into seven (7) groups of eight (8) rats each. Group 1 was control rats; Groups 2-7 served as the experimental groups. After 6 weeks treatment duration, the rats were euthanized, semen was collected for semen analysis, blood samples for testosterone, and FSH and LH assay determination, and left testes was harvested for histological analysis. One-way ANOVA was used to compare means at p-level < 0.05 was considered significant. Findings from this study have shown that alcohol and cadmium chloride adversely affected semen parameters, testosterone, and FSH and LH hormone milieu. Data also showed that Silymarin administration attenuated the adverse effect of alcohol and cadmium chloride on semen quality and hormones associated with reproductive functions. Hence, Silymarin mopped the effect of in vivo attenuation of alcohol and cadmium chloride testicular damage. The findings of this study have further established that alcohol and cadmium chloride adversely affected semen parameters, testicular alterations, and serum hormonal milieu. However, the effect was more significantly deleterious in rats exposed to cadmium chloride when compared to rats exposed to alcohol, subsequently alcohol- and cadmium chloride-induced degeneration of testicular tissues. Furthermore, Silymarin administration attenuated the adverse effect of alcohol on semen quality and hormones associated with reproductive functions.