Naringin abrogates angiotensin-converting enzyme (ACE) activity and podocin signalling pathway in cobalt chloride-induced nephrotoxicity and hypertension.

PurposeThe persistent and alarming rates of increase in cardiovascular and renal diseases caused by chemicals such as cobalt chloride (CoCl2) in mammalian tissues have led to the use of various drugs for the treatment of these diseases. This study aims at evaluating the nephron-protective action of Naringin (NAR), a metal-chelating antioxidant against CoCl2-induced hypertension and nephrotoxicity.MethodsForty-two male Wistar rats were randomly distributed to seven rats of six groups and classified into Group A (Control), Group B (300 part per million; ppm CoCl2), Group C (300 ppm CoCl2 + 80 mg/kg NAR), Group D (300 ppm CoCl2 + 160 mg/kg NAR), Group E (80 mg/kg NAR), and Group F (160 mg/kg NAR). NAR and CoCl2 were administered via oral gavage for seven days. Biomarkers of renal damage, oxidative stress, antioxidant status, blood pressure parameters, immunohistochemistry of renal angiotensin-converting enzyme and podocin were determined.ResultsCobalt chloride intoxication precipitated hypertension, renal damage, and oxidative stress. Immunohistochemistry revealed higher expression of angiotensin-converting enzyme (ACE) and podocin in rats administered only CoCl2.ConclusionTaken together, the antioxidant and metal-chelating action of Naringin administration against cobalt chloride-induced renal damage and hypertension could be through abrogation of angiotensin-converting enzyme and podocin signalling pathway.

Clofibrate, a Peroxisome Proliferator-Activated Receptor-Alpha (PPARα) Agonist, and Its Molecular Mechanisms of Action against Sodium Fluoride-Induced Toxicity.

Sodium fluoride (NaF) is one of the neglected environmental pollutants. It is ubiquitously found in the soil, water, and environment. Interestingly, fluoride has been extensively utilized for prevention of dental caries and tartar formation, and may be added to mouthwash, mouth rinse, and toothpastes. This study is aimed at mitigating fluoride-induced hypertension and nephrotoxicity with clofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist. For this study, forty male Wistar rats were used and randomly grouped into ten rats per group, control, sodium fluoride (NaF; 300 ppm) only, NaF plus clofibrate (250 mg/kg) and NaF plus lisinopril (10 mg/kg), respectively, for 7 days. The administration of NaF was by drinking water ad libitum, while clofibrate and lisinopril were administered by oral gavage. Administration of NaF induced hypertension, and was accompanied with exaggerated oxidative stress; depletion of antioxidant defence system; reduced nitric oxide production; increased systolic, diastolic and mean arterial pressure; activation of angiotensin-converting enzyme activity and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB); and testicular apoptosis. Treatment of rats with clofibrate reduced oxidative stress, improved antioxidant status, lowered high blood pressure through the inhibition of angiotensin-converting enzyme activity, mineralocorticoid receptor over-activation, and abrogated testicular apoptosis. Taken together, clofibrate could offer exceptional therapeutic benefit in mitigating toxicity associated with sodium fluoride.

The therapeutic potential of the novel angiotensin-converting enzyme 2 in the treatment of coronavirus disease-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 2019 (COVID-19). This virus has become a global pandemic with unprecedented mortality and morbidity along with attendant financial and economic crises. Furthermore, COVID-19 can easily be transmitted regardless of religion, race, sex, or status. Globally, high hospitalization rates of COVID-19 patients have been reported, and billions of dollars have been spent to contain the pandemic. Angiotensin-converting enzyme (ACE) 2 is a receptor of SARS-CoV-2, which has a significant role in the entry of the virus into the host cell. ACE2 is highly expressed in the type II alveolar cells of the lungs, upper esophagus, stratified epithelial cells, and other tissues in the body. The diminished expressions of ACE2 have been associated with hypertension, arteriosclerosis, heart failure, chronic kidney disease, and immune system dysregulation. Overall, the potential drug candidates that could serve as ACE2 activators or enhance the expression of ACE2 in a disease state, such as COVID-19, hold considerable promise in mitigating the COVID-19 pandemic. This study reviews the therapeutic potential and pharmacological benefits of the novel ACE2 in the management of COVID-19 using search engines, such as Google, Scopus, PubMed, and PubMed Central.

Potential health benefits of zinc supplementation for the management of COVID-19 pandemic.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent for the Coronavirus Disease 2019 (COVID-19). The COVID-19 pandemic has created unimaginable and unprecedented global health crisis. Since the outbreak of COVID-19, millions of dollars have been spent, hospitalization overstretched with increasing morbidity and mortality. All these have resulted in unprecedented global economic catastrophe. Several drugs and vaccines are currently being evaluated, tested, and administered in the frantic efforts to stem the dire consequences of COVID-19 with varying degrees of successes. Zinc possesses potential health benefits against COVID-19 pandemic by improving immune response, minimizing infection and inflammation, preventing lung injury, inhibiting viral replication through the interference of the viral genome transcription, protein translation, attachment, and host infectivity. However, this review focuses on the various mechanisms of action of zinc and its supplementation as adjuvant for vaccines an effective therapeutic regimen in the management of the ravaging COVID-19 pandemic. PRACTICAL APPLICATIONS: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent for the Coronavirus Disease 2019 (COVID-19), has brought unprecedented untold hardship to both developing and developed countries. The global race for vaccine development against COVID-19 continues with success in sight with attendant increasing hospitalization, morbidity, and mortality. Available drugs with anti-inflammatory actions have become alternative to stem the tide of COVID-19 with attendant global financial crises. However, Zinc is known to modulate several physiological functions including intracellular signaling, enzyme function, gustation, and olfaction, as well as reproductive, skeletal, neuronal, and cardiovascular systems. Hence, achieving a significant therapeutic approach against COVID-19 could imply the use of zinc as a supplement together with available drugs and vaccines waiting for emergency authorization to win the battle of COVID-19. Together, it becomes innovative and creative to supplement zinc with currently available drugs and vaccines.

Non-Dose-Dependent Changes in Liver Enzyme Levels of Children With Epilepsy on Treatment With Sodium Valproate.

BACKGROUND: Sodium valproate (VPA) is considered as the drug of choice for the treatment of generalized epilepsy in children. Sodium Valproate may be hepatotoxic. AIM: To assess the level of derangement of liver enzymes in children with epilepsy on treatment with sodium valproate. METHODS: A cohort study. One hundred fifty-three children, comprising 51 with epilepsy on treatment with VPA (group I), 51 with epilepsy on treatment with other antiepileptic drugs (AEDs) but not VPA (group II), and 51 with nonconvulsive disorders (group III) had liver function tests performed for them. Data were analyzed by SPSS version 23.0. RESULTS: There were 85 males and 68 females, aged 6 months to 14 years (median = 7.0 years). There was no significant difference in the mean plasma levels of alanine transaminase (ALT), alkaline phosphatase, and gamma glutamyl transferase across the three groups of children. The mean aspartate transaminase level was significantly higher in children in group III. There was a statistically significant negative correlation between the duration of AED therapy and the mean serum level of AST (r = -0.266, P = 0.016). The serum ALT level showed a statistically significant positive correlation with the duration of AED therapy (r = 0.268, P = 0.015). CONCLUSION: Sodium valproate monotherapy does not appear to be associated with significant hepatotoxicity in children in our cohort.

Hypolipidemic Effect of Chrysophyllum albidum Peel Extract and Its Underlying Antioxidant Mechanisms in Normal and Triton-X-100-Induced Hyperlipidemic Rats.

Chrysophyllum albidum peel ethanol extract (CAPEE) was investigated for its antioxidant and hypolipidemic effects in rats. Dried peel was extracted in 70% ethanol and tested for phenolic content and in vitro antioxidant properties. Acute toxicity effect of CAPEE was tested at dose level of 2,000 mg/kg. The antioxidant and hypolipidemic effects in serum and hepatic tissues were evaluated in normal and triton-X-100-injected rats following 14 days of repeated treatment with CAPEE (50 and 200 mg/kg). Total phenolic content (TPC) and total flavonoid content (TFC) of CAPEE were 49.49 ± 2.48 mg GAE/g of sample and 14.71 ± 0.90 mg RE/g sample, respectively. The extract scavenged DPPH radical in a concentration-dependent manner with an IC50 of 63.1 ± 0.5 µg/mL. CAPEE (2,000 mg/kg) showed no sign of toxicity in mice. CAPEE (50 and 200 mg/kg) did not alter lipid profile in normal rats but ameliorated triton-X-100-induced increases in triglycerides and cholesterol and decrease in high-density lipoprotein (HDL). CAPEE showed hepatoprotective as well as antioxidant activity in serum and liver of normal and hyperlipidemic rats. The results revealed that Chrysophyllum albidum fruit peel ethanol extract possesses antioxidants and hypolipidemic properties.

Antihypertensive prescription among black patients without compelling indications: prescription, effectiveness, quality and cost of medication.

BACKGROUND: Hypertension remains one of the leading causes of death in Nigeria. Appropriate and cost-effective treatment of the disease is necessary to reduce mortality. This study evaluates (i) the prescription patterns and quality (ii) blood pressure control and (iii) cost of medication among patients with hypertension uncomplicated by co-morbid diseases or compelling indications. METHOD: Patients with uncomplicated hypertension attending three clinics in the University College Hospital, Ibadan in Nigeria were recruited into this study. Information on demographics, antihypertensive medication prescribed, blood pressure measurements, and cost of medications were collected for each patient. Antihypertensive medications were classified according to the Anatomical Therapeutic Chemical (ATC) classification system and the Defined Daily Dose (DDD) system. The frequency of usage of each drug class and their prescribed doses per patient/day were calculated and compared with the DDD to assess the quality of prescription. Cost of antihypertensive medication was calculated for each patient and reported as cost per patient/day and cost per patient/month. Effect of variables on BP control was ascertained. Statistical analyses were done using SPSS, chi-square and correlation test was used to test for associations. RESULT: A total number of 1050 hypertensive patients were included in this study. The mean age was 60 years, females made up 62% of the study population. A high level of polypharmacy (87%) and sub-optimal blood pressure control was observed. An increase in blood pressure was observed with increase in the number of medication prescribed (χ2 = 33.618, p < 0.001; r = .18, p < 0.001). The most prescribed antihypertensive medication either as a single therapy or a fixed-dose combination was diuretic. About 54% of the prescribed daily doses of antihypertensive medication exceeded the DDD. The total monthly expenditure on antihypertensive drugs was approximately N3.2 million ($15,300). CONCLUSION: Study findings show a high level of polypharmacy and non-generic prescribing. Increased prescribing of drugs that are cost-effective, as well as prescription of fixed dose combinations (FDCs), is recommended in hypertensive patients. This is necessary to control blood pressure while increasing treatment adherence.