Possible mechanisms involved in the protective effect of lutein against cyclosporine-induced testicular damage in rats.

Oxidative stress and aberrant inflammatory response have important implications in cyclosporin-induced reproductive functions. Previous studies have shown that agents with antioxidant and anti-inflammatory activities might be beneficial in reversing cyclosporin-induced reproductive impairment. Lutein is a naturally occurring compound with antioxidant and anti-inflammatory properties. However, the effect of lutein against cyclosporin-induced reproductive impairment remains in complete. Hence, we investigated the protective effect of lutein, specifically focusing on the role of nuclear factor erythroid 2 related factor-2 (Nrf2)/heme-oxygenase-1 (HO-1)/connexin-43 (Cx-43) upregulation system against cyclosporine-induced reproductive impairment. Six male Wistar rats were allotted into 5 groups and given daily gavage of cyclosporine (40 mg/kg) and/or lutein (30 mg/kg) for four (4) weeks or in combination, respectively. The testicular antioxidant scaffolds: superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), add to sulfhydryl (T-SH), non-protein sulfhydryl (NP-SH), glutathione reductase (GR), glutathione-S -transferase (GST), glutathione peroxidase (GSH-Px), thiobarbituric acid reactive substances (TBARS), myeloperoxidase (MPO), testicular proinflammatory cytokines, apoptotic related protein, nucleic acids, sialic acid, testicular proton pump ATPase, stress responsive protein, BTB-related protein and total protein levels in the testes were assayed thereafter. Cyclosporin significantly increased NOX-1, TNF-α, IL-1ß, MPO, caspase-3 and -9 levels, which were reversed by lutein. Lutein reversed cyclosporin-induced decreases in Nrf2, HO-1, BCL-2, cytochrome C, with corresponding increase in CAT, SOD, GSH, T-SH, NP-SH, GST, GR, GSH-Px, and Cx-43 levels compared to cyclosporin groups. Lutein also abates cyclosporin-induced alterations Na + -K + -ATPase activities. Our findings showed that lutein's protective effect against cyclosporin-induced reproductive impairment might be associated with mechanisms linked to its antioxidant, anti-apoptotic, and anti-inflammatory properties, notably through up-regulation of Nrf2/HO-1/Cx-43 signaling and down-regulation of NOX-1 signaling.

Geraniol attenuates behavioral and neurochemical impairments by inhibitions of HPA-axis and oxido-inflammatory perturbations in mice exposed to post-traumatic stress disorder.

Geraniol is an acyclic isoprenoid monoterpenoid analogue that has been shown to elicit neuroprotective functions, primarily through its ability to stimulate antioxidant and anti-inflammatory systems. An increase in inflammatory cytokines and oxidative stress exacerbate activation hypothalamic-pituitary-adrenal axis (HPA), leading to neurochemical dysfunction, which has important roles in the pathogenesis of post-traumatic disorder (PTSD), a mental health disorder characterized of post-trauma-induced intense fear. The aim of this study was to evaluate the anti-PTSD-like effects and underlying mechanisms of geraniol against single-prolonged-stress (SPS)-induced PTSD in mice. Following concomitant exposure to SPS (triple-paradigm traumatic events) and isolation for 7 days, mice (n = 9) were treated with geraniol (50 and 100 mg/kg, p.o.) or fluoxetine (10 mg/kg, p.o.) from days 8-21. Mice were assessed for behavioral changes. Neurochemical changes, inflammatory, oxido-nitrergic markers, adrenal weight, serum glucose and corticosterone concentrations were assayed. Geraniol inhibits SPS-induced anxiety- and depressive-like features as well as behavioral despair in the depression paradigms. SPS-induced locomotor and memory impairments were also abated by geraniol treatment similarly to fluoxetine. SPS-induced adrenal hypertrophy and increased blood glucose and corticosterone concentrations, were attenuated by the geraniol treatment. Elevated levels of TNF-α and IL-6, and malondialdehyde, nitrite, acetylcholinesterase enzyme were reduced by geraniol. Geraniol also increased glutathione, superoxide-dismutase, and catalase levels as well as dopamine, serotonin concentrations and GABAergic glutamic acid decarboxylase enzyme activity in the striatum, prefrontal cortex and hippocampus in the PTSD-mice relative to SPS control. In conclusion, geraniol attenuates behavioral impairments and neurochemical dysregulations by inhibitions of HPA-axis and oxido-inflammatory perturbations in mice exposed to PTSD.

Co-administration of metformin and/or glibenclamide with losartan reverse NG-nitro-l-arginine-methyl ester-streptozotocin-induced hypertensive diabetes and haemodynamic sequelae in rats.

Over the years, there have been opinions on whether to reduced blood pressure (BP) to a different levels in patients with diabetes mellitus. Hence, this study investigated the efficacy of the co-administration of losartan (angiotensin receptor blocking antihypertensive agent) with metformin and/or glibenclamide (antidiabetic agents) on hypertensive-diabetic experimental rats induced by NG-nitro-l-arginine-methyl-ester hydrochloride (l-NAME), and streptozotocin (STZ). STZ (45 mg/kg, i.p.)-induced diabetic rats combined with l-NAME (40 mg/kg, p.o.)-induced hypertension were allotted into different groups. Group 1 received distilled water (10 mL/kg) and served as normal control, group 2 comprised hypertensive diabetic rats with distilled water, groups 3-5 were hypertensive-diabetic rats but received combination treatments of losartan + metformin, losartan + glibenclamide, and losartan + metformin + glibenclamide daily for 8 weeks, respectively. Our finding revealed no changes in the body weights, but there was a significant increase in fasting blood sugar levels in l-NAME - STZ-induced hypertensive-diabetes, which were lowered by losartan + metformin, losartan + glibenclamide, and losartan + metformin + glibenclamide treatments. Moreover, the increased systolic-BP, mean arterial pressure but not diastolic-BP and heart rate by l-NAME + STZ were attenuated more significantly by losartan + metformin + glibenclamide between weeks 2-8 relative to hypertensive-diabetic control. l-NAME + STZ-induced elevated levels of lactate dehydrogenase and creatinine kinase, were differentially reversed by losartan + metformin, losartan + glibenclamide, and losartan + metformin + glibenclamide. However, l-NAME + STZ-induced decreased nitrite level was significantly restored by all treatments, suggesting increased nitrergic transmission. Additionally, l-NAME + STZ-induced degeneration of pancreatic islet and myocardial cells were dramatically alleviated by losartan + metformin + glibenclamide treatments. Our findings suggest hyperglycemia with raised systolic-BP should be managed with losartan combined with both metformin and glibenclamide than single combination of losartan with antidiabetics.

COVID-19 pandemic: the implications of the natural history, challenges of diagnosis and management for care in sub-Saharan Africa.

BACKGROUND: Coronavirus disease (COVID-19) is a severe acute respiratory infection which has afflicted virtually almost all nations of the earth. It is highly transmissible and represents one of the most serious pandemics in recent times, with the capacity to overwhelm any healthcare system and cause morbidity and fatality. MAIN CONTENT: The diagnosis of this disease is daunting and challenging as it is dependent on emerging clinical symptomatology that continues to increase and change very rapidly. The definitive test is the very expensive and scarce polymerase chain reaction (PCR) viral identification technique. The management has remained largely supportive and empirical, as there are no officially approved therapeutic agents, vaccines or antiviral medications for the management of the disease. Severe cases often require intensive care facilities and personnel. Yet there is paucity of facilities including the personnel required for diagnosis and treatment of COVID-19 in sub-Saharan Africa (SSA). It is against this backdrop that a review of key published reports on the pandemic in SSA and globally is made, as understanding the natural history of a disease and the documented responses to diagnosis and management is usually a key public health strategy for designing and improving as appropriate, relevant interventions. Lead findings were that responses by most nations of SSA were adhoc, paucity of public health awareness strategies and absence of legislations that would help enforce preventive measures, as well as limited facilities (including personal protective equipment) and institutional capacities to deliver needed interventions. CONCLUSION: COVID-19 is real and has overwhelmed global health care system especially low-income countries of the sub-Sahara such as Nigeria. Suggestions for improvement of healthcare policies and programs to contain the current pandemic and to respond more optimally in case of future pandemics are made herein.