Safety and Efficacy of Methanol Fraction of Moringa oleifera as Antihypertensive in L-NAME Induced Hypertensive Rabbits: Bedside to Bench, Implications for Bench Back to Bedside

Context: Hypertension, a global menace requires innovative research into the use of Moringa oleifera being promoted and traditionally used as alternative therapy.Objective: To innovatively evaluate the mechanistic effect, safety and efficacy of the methanol fraction of M. oleifera (MMO) leaves on L-NAME induced hypertensive rabbits.Methods: Rabbits were divided into six groups: Control, L-NAME alone, L-NAME with 100, 200 or 400 mg/kg of MMO and enalapril. Inclusion and exclusion criteria were similar baseline parameters and Day 3 systolic blood pressure (SBP) less than baseline SBP respectively. The primary outcome was a 10% reduction of SBP on Day 21. Enalapril group was excluded from analysis. Safety was assessed with liver and renal functions, hydrogen peroxide and nitric oxide concentrations to elucidate mechanistic effect.Results: Moringa 100 mg/kg, 200 mg/kg and 400 mg/kg reduced SBP by 4.75, 18.00 and 15.25 mmHg (F=22.123, p=0.000). SBP control was achieved with MMO 200mg/kg, 14% reduction and 400mg/kg, 12% reduction. Nitric oxide concentration, 0.06, 0.094 and 0.114mmol (F= 30.255, p= 0.000) dose-dependently increased and was most predictive of SBP control (r2=0.802, p=0.000). Nitric oxide production was inversely related to heart/body weight ratio which was dose-dependently reduced. MMO reduced hydrogen peroxide and ALT level but no significant effect on urea, HDL, and TG.Conclusion: MMO reduced SBP and dose-dependently increased nitric oxide concentration in L-NAME induced hypertensive rabbits. The effect may be mediated via activation of nitric oxide pathway. MMO demonstrated a potent anti-oxidant activity and safety. Effect on ventricular hypertrophy needs further evaluation

Osteodystrophia fibrosa secondary to a chronic renal failure in a dog: A case report

A five year male Rottweiler was presented to the Small animal clinic of the Veterinary Teaching Hospital, University of Ibadan, being a referral from Lagos. Bilateral swelling and deformity of the skull bones were observed. Palpation revealed swollen gums and weak mobile teeth weak. Urination was frequent and the urine very clear. Haematology and blood chemistry revealed non-regenerative anaemia, mild leucopenia, hypocalcaemia, hyper-phosphataemia, high serum blood urea and creatinine, and hyper-bilirubinaemia. Treatment was instituted with dextrose saline to rehydrate the animal and correct electrolyte and metabolic disorders. The dog however died despite intervention. At post mortem, the carcass was found to be jaundiced, the premolars were mal-positioned. Calcification was visible on the lower jaw. Kidneys were small, firm, with many white specks on the cortical surface. A diagnosis of Uremic renal failure with Osteodystrophia fibrosa (renal rickets) was made. The possible causes and clinical implications of the condition were discussed

Target organ damage in canine and feline systemic hypertension: a review

Hypertension is a state of persistent elevation of arterial blood pressure and a major risk factor for cardiovascular diseases. Chronic exposure to blood pressure results in target organs damage (TOD). Hypertension may be primary or essential and symptoms may be subclinical, insidiously causing damages to the target organs. It is often diagnosed when condition relating to the organ dysfunction are presented to the clinic. On the other hand, hypertension can be secondary when it is caused by an underlying condition and it may eventually damage some other vital organs (Target organs) in the body of the affected animal. These target organs include the eyes, brain, kidneys and heart causing hypertensive retinopathy, neuropathy, nephropathy and cardiomyopathy, respectively, in the organs. This review elucidates the occurrence and manifestation of hypertension and pathophysiology and clinical manifestation of target organ damage in small animals. There is therefore, the need for comprehensive cardiovascular examination and measurements of renal function, echocardiography and electrocardiography to diagnose hypertension and target organ damage early in order to promptly and properly manage the health abnormality. This will reduce the economic loss, organ damage and mortality caused by hypertension and its associated organ dysfunction

Phytochemical profiling, antioxidant activities and essential oil constituents of Andrographis paniculata

Oxidative stress is involved in the pathogenesis of various diseases which lead to urgent need to investigate new, safe and effective source of antioxidant agents. This research proposed to investigate in-vitro and phytochemical constituent of the plant Andrographis paniculata using phytochemical analysis, GC/MS, DPPH, ABTS, FRAP and NO. Phytochemical analysis of Andrographis paniculata revealed the presence of tannins, total flavonoids, total phenol, total flavonols, and total proanthocyanidins. GC/MS analysis of essential oil of AP identified one major compound name benzenepropanoic acid elucited at 3.296 retention time and 0.74 area percentage. The ferric reducing potential of the extracts was concentration dependent and significantly different from that of rutin and vitamin E. The % inhibition of ABTS by the ethanol leaf extract of Andrographis paniculata was concentration dependent and compared favourably well with the rutin and vitamin E. In DPPH scavenging assays, the IC50 value of the ethanol leaf extract of Andrographis paniculata was < 0.025 mg/ml, while IC50 of rutin and Vitamin E were < 0.025 mg/ml and 0.08mg/ml. Nitric oxide IC50 for extract is 1.05mg/ml, Vitamin E is 1.2 mg/ml, and rutin is < 0.025 mg/ml. The present study showed high level of radical scavenging activity by ethanol leaf extract of Andrographis paniculata with higher antioxidant activities than Vitamin E but less than that of rutin. This show that Andrographis paniculata has antioxidant properties and the plant could be used in the prevention and treatment of diseases associated with oxidative stress.Keywords: Andrographis paniculata, Antioxidants, Oxidative stres

Effect of arsenic acid withdrawal on hepatotoxicity and disruption of erythrocyte antioxidant defense system

We investigated the effects of withdrawal from Sodium arsenite (NaAsO2) on the hepatic and antioxidant defense system in male Wistar rats using a before and after toxicant design. Rats were orally gavaged daily with varying doses of NaAsO2 for a period of 4 weeks. One half of the population was sacrificed and the remaining half had the toxicant withdrawn for another further 4 weeks. Biochemical and immunohistochemical techniques were used to assess the impact of withdrawal on the erythrocyte and hepatic systems. Exposure of Wistar rats to NaASO2 led to a significant (p < 0.05) increase in hepatic and erythrocyte markers of oxidative stress (malondialdehyde, thiol contents and hydrogen peroxide generation). Concurrently, there was a significant (p < 0.05) increase in hepatic and erythrocyte antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and superoxide dismutase) following exposure. Withdrawal from NaAsO2 exposure led to a decline in both erythrocyte and hepatic markers of oxidative stress and together with a significant improvement in antioxidant defense system. Histopathology and immunohistochemistry revealed varying degrees of recovery in hepatocyte ultrastructure alongside increased expression of the pro-survival protein Kinase B (Akt/PKB) after 4 weeks of NaAsO2 withdrawal. Conclusively, withdrawal from exposure led to a partial recovery from oxidative stress-mediated hepatotoxicity and derangements in erythrocyte antioxidant system through Akt/PKB pathway. Keywords: Liver, Erythrocyte, Arsenic acid, Hepatotoxicity, Oxidative stress, Akt/PKB signalin

The ethanol leaf extract of Moringa oleifera leaf extract blunts isoproterenol-induced cardiotoxicity in rats through mitigation of free radical production and down regulation of cardiac troponin and nuclear factor kappa B

Heart disease including coronary artery disease, ischemic heart disease and myocardial infarction is a leading cause of death in the world. Moringa oleifera is a popular plant in folkloric medicine. This study evaluated the effect of the ethanol leaf extract of Moringa oleifera (ELMO) on isoproterenol-induced myocardial infarction in rats. Thirty five male Wistar rats were randomly divided into 5 groups of 7 animals per group i.e. Group A (control), Group B (Toxicant), Groups C and D animals were given 50 mg/kg and 100 mg/ kg of (ELMO), respectively for 7 days and on day 8 were given 100mg/kg of isoproterenol. Group E animals received 100 mg/kg of ELMO only for 7 days. Serum analysis of CK- MB, Myeloperoxidase, Nitric oxide and Total protein, heart harvested for biochemical assays for the analysis of Advanced oxidative protein product (AOPP), Protein carbonyl (PC), Malonaldehyde (MDA), Superoxide dismutase (SOD), Glutathione transferase (GST), Reduced glutathione (GSH), Glutathione peroxidase (GPx), Total thiol, Non-protein thiol and Hydrogen peroxide generation), histology and immunohistochemistry (CTnI, NF-KB) were carried out. There was significant (p &lt; 0.05) reduction in SOD, GPx, GST, increased myeloperoxidase, Protein carbonyl, AOPP, MDA levels and H2O2 generation in toxicant groups but there was corresponding increase in the antioxidant enzymes and decrease in markers of oxidative stress and inflammation in ELMO treated groups. The toxicant also caused severe histopathological changes in the heart tissues and these were corrected by all the doses of the extract. There was increase expression of CTnI and NF-KB in the toxicant group but down regulation of these proteins by the extract. The results showed that Moringa oleifera possess cardiac protective effect