DEPARMENT OF PHARMACOLOGY AND TOXICOLOGY

Isoniazid is a widely used drug in tuberculosis treatment regimens. Its application in direct observed therapy short course ”(DOTS) along with other medications has been well documented to be efficacious and effective. However, since its introduction over 70 years ago, it has been found to possess adverse effects as the induction of neuropathies. There are estimates that as many as 10 % of patients receiving isoniazid will develop some form of neuropathy. Introduction of new medications to stop these neuropathies still pose a challenge. Pyridoxine (vitamin B6) is currently recommended with isoniazid therapy to avert induction of neuropathy. Although ,the potential of vitamin C as an antioxidant to prevent induced neuropathies has been suggested based on previous studies, the findings from this study were intended to contribute valuable insights into the potential therapeutic role of vitamin C as an adjuvant to mitigate neuropathic complications in isoniazid- based therapies. Using well-established animal models, we assessed the effects of vitamin C supplementation on the development and progression of some neuropathic symptoms induced by isoniazid administration. Male Wistar rats were divided into six groups: control, isoniazid-treated (800 mg/kg), and combination-treated; Isoniazid with vitamin C in low (7.5 mg/kg), medium (15 mg/kg), high (30 mg/kg) daily doses and isoniazid with pyridoxine (50 mg/kg). Behavioural assessments, including sensory and motor function tests, were conducted at the end of a seven day period to monitor the onset and severity of neuropathy. In conclusion, our findings revealed that isoniazid administration led to a significant decline in sensory and motor functions indicative of peripheral nerve damage. Vitamin C supplementation did not demonstrate a remarkable attenuation of these neuropathic manifestations. Rats co- administered with isoniazid and vitamin C did not exhibit any improvement in sensory and motor functions when compared with the control and standard therapy of pyridoxine. These results negate the potential neuroprotective effects of vitamin C against isoniazid-induced peripheral neuropathy

Twenty male wistar rats were randomly assigned to four groups (n = 5). Group I (control)received dis tilled water, while Groups II, III, and IV received 150 mg/kg, 300 mg/kg, and 600 mg/kg of Moringa oleifera extract, respectively, via oral administration for 28 days. Body weights were taken in a weekly schedule, major organs (heart, kidney, liver, lungs and spleen) were harvested, weighed, preserved for histopathological investigations and organ weight index was calculated. Data were analyzed using GraphPad Prism, with a statistical significance level of p < 0.05. The extract caused continuous body weight gain in all the treatment groups and there were no significant differences between them with the control showing that the metabolic and physiological functioning was preserved. The organ weight index of the liver, kidney, heart, spleen and the lungs were normal and did not show any hypertrophy or atrophy based on the doses. The histopathological examination showed minimal hepatic steatosis in the control group, and moderate steatosis at 600 mg/kg, no necrosis or inflammation. There was normal tissue in the kidneys, heart and spleen. The lungs of the rats treated with 300 mg/kg and 600 mg/kg, however, had diffuse alveolar damage that was characterized by intra-alveolar edema, hyaline membrane deposition, and neutrophilic infiltration which is a phenomenon that indicates dose￾related pulmonary sensitivity. In general, the extract showed relative systemic safety at both low and moderate doses, although the development of diffuse alveolar damage at 300 mg/kg and 600 mg/kg means that the respiratory risk may occur at higher exposures. More experiments and mechanistic research are ix also advised in order to completely prove the safety of Moringa oleifera root extract in the long term

This study used mouse models to assess the acute toxicity and analgesic effects of Moringa oleifera extract. Acute toxicity was tested by giving different oral dose up to 5000 mg/kg, which resulted in no mortality, showing relative safety. The analgesic efficacy was assessed using acetic acid-induced writhing and formalin-induced paw licking assays. The extract considerably reduced writhing behaviors in a dose-dependent manner (p < 0.05), indicating peripheral analgesic effects. In the formalin test, the extract significantly reduced paw licking time in both neurogenic (early) and inflammatory (late) phases, with significant effects at moderate and high dosages (p < 0.05), indicating wide analgesic and antiinflammatory activities. These data confirm Moringa oleifera extract's potential as a safe and effective analgesic agent. Moringa oleifera's phytochemical components, which include flavonoids, alkaloids, saponins, tannins, and phenolic acids, are thought to work together to provide analgesic and anti-inflammatory benefits. The extract's ability to attenuate nociceptive behaviors in established experimental models backs up its longstanding use in folk medicine to treat pain and inflammation. The findings of this work give experimental confirmation for Moringa oleifera root bark as a promising natural analgesic with a wide range of efficacy, prompting further investigation into its pharmacological mechanisms and possible clinical applications. The extract's analgesic efficacy and safety profile make it a promising lowrisk pain management option

Background: Pain and inflammation remain major health concerns that reduce quality of life despite many available treatments. Diclofenac, a nonsteroidal anti-inflammatory drug, and orphenadrine, a centrally acting muscle relaxant, target different pain pathways. This study investigates whether their combined use enhances analgesic and anti-inflammatory effects, offering a safer and more effective approach to pain management. Method: Twenty-four Swiss albino mice were divided into four groups to receive saline, diclofenac (50 mg/kg), orphenadrine (25 mg/kg) and ophenadrine-diclofenac (25 mg/kg-50 mg/kg). Analgesic effects were assessed using the acetic acid–induced writhing and hole- board tests, while COX inhibition was evaluated using the quantitative polymerase chain reaction assay. Data were expressed as Mean ± SEM and analyzed using one-way ANOVA, with significance set at p < 0.05. Result: Diclofenac (1.67 ± 0.76), orphenadrine (2.17 ± 0.95), and their combination (0.00 ± 0.00) significantly reduced writhes compared to control (6.00 ± 1.53; p < 0.05). COX-2 levels were markedly lower in diclofenac (88.32 ± 1.18), orphenadrine (27.59 ± 2.26), and combination (68.30 ± 1.43) treated groups versus control (95.26 ± 1.88). In the hole-board test, the combination group (24.33 ± 1.59) maintained head dips comparable to the control group. Conclusion: Diclofenac and orphenadrine provide complementary pain relief, with diclofenac acting peripherally and orphenadrine centrally. Their combination synergistically abolished writhing, balanced COX-2 activity, and preserved normal exploratory behaviour. These results highlight the diclofenac–orphenadrine combination as an effective multimodal analgesic that enhances pain control while supporting central function.

Cardiovascular Diseases (CVD’s) remain the dominant course of mortality in developed and developing countries. Due to changing life styles, socio-economic status and decline in provision of healthcare services in developing countries such as Nigeria, myocardial infraction is making a significant contribution to national healthcare burden and mortality statistics.
Aim: This present study evaluated the effect of aqueous extract of Gnetum africanum on some cardiac function biomarkers in isoprenaline-induced myocardial infarction in rats.
Methodology: Acute toxicity test and haemotological and biochemical analysis of the extract was done using standard methods. Wister rates aged 2 – 3 months weighing 150 to 200 grams were acclimatized for 2 weeks and grouped into 4 (A– D) groups. B and C orally received graded doses of extracts (B = 50, C = 100, mg/kg body weight) daily for 28 days. Group A served as control and group D served as standard group 2ml/kg of cargradenol Blood samples (5ml) were collected into ethylene diamine tetracetic acid (EDTA) containers and analysed using haemetological automety following manufacturers guidelines. Isoprenaline was induced 85mg/kg on 26th and 27th day in all groups.
Result Gnetum africanium extract displayed no accurate toxicity up to 5g/kg; at doses of 50mg/kg and 100mg/kg, it demonstrated no significant effects on cardiac biomarkers when compared with the control against isoprenaline-induced myocardial injury in rats across parameters including organ weight, body weight changes, cardiac biomarkers and oxidative-antioxidant balances