Serum biochemical changes accompanying prolonged administration of ethanolic extract of whole fruit of Lagenaria breviflora (Benth) Roberty in Wistar rats

Toxicological evaluation of the whole fruit of Lagenaria breviflora was carried out using the serum  biochemical changes accompanying prolonged administration of the ethanolic extract of the fruit in Wistar rats. Twenty five rats were randomly but equally divided into five groups. Rats in groups B, C, D and E were administered with ethanolic extract at 1000, 2000, 4000 and 8000 mg/kg body weight, respectively, while rats in group A received 0.9% physiological saline as the control animals. The lower doses of the extract (1000 and 2000 mg/kg body weight) lowered the serum levels of total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C), while high-density    lipoproteincholesterol (HDL-C) was elevated. Higher doses of 4000 and 8000 mg/kg body weight of the extract increased the serum levels of TG and LDL-C and, lowers HDL-C level in the serum. There was dosedependent elevation of serum glucose level in rats administered with the extract. The serum value ofglucose in rats administered with the extract of 8000 mg/kg body weight increased two and half-foldover the control value. The mean serum total protein value increased for all the treatment groups whencompared with that of the rats in the control group. The serum creatinine (CRT) level increased   dosedependently and blood urea nitrogen (BUN) was elevated two-fold in most of the test groups. This was corroborated with histopathological findings revealing marked renal tubular degeneration. The serumlevel of ALP increased significantly (P < 0.05) in test rats administered the highest dose of the extract. Itwas concluded that therapeutic application of the extract of L. breviflora is quite safe at lower doses butit is nephrotoxic and can precipitate hyperglycaemia and dyslipidaemia at higher doses. Key words: Toxicological evaluation, Lagenaria breviflora, fruit, serum biochemistry, Wistar rat

Antihypertensive power of Naringenin is mediated via attenuation of mineralocorticoid receptor (MCR)/ angiotensin converting enzyme (ACE)/ kidney injury molecule (Kim-1) signaling pathway

Please read abstract in the article.Cape Peninsula University of Technology and National Research Foundation (South Africa).https://www.elsevier.com/locate/ejpharhj2023Paraclinical Science

Antihypertensive action of Launaea taraxacifolia and its molecular mechanism of action

Launaea taraxacifolia has been traditionally used for the management of conditions such as cardiovascular, respiratory, and metabolic diseases. High blood pressure was established by oral administration of L-Nitro Arginine Methyl Ester (L-NAME) a non-selective inhibitor of endothelial nitric oxide synthase (eNOS). The antihypertensive action of the methanol leaf extract of L. taraxacifolia was examined. Fifty male Wistar rats were divided into 5 groups of 10 animals per group: Group A (Distilled water), Group B (Hypertensive rats; 40mg/kg L-NAME), Group C (Hypertensive rats plus 100 mg/kg extract), Group D (Hypertensive rats plus 200 mg/kg extract) and Group E (Hypertensive rats plus 10mg/kg of Lisinopril). The treatments were orally administered for five weeks. Haemodynamic parameters, urinalysis, indices of oxidative stress and immunohistochemistry were determined. Findings from this study showed that blood pressure parameters, urinary sodium and indices of oxidative stress increased significantly while Invivo antioxidant defence systems decreased significantly in hypertensive rats. Immunohistochemistry revealed significant increases in expressions of mineralocorticoid receptor, angiotensin converting enzyme activity and kidney injury molecule-1 in kidney of hypertensive rats. Treatment with Launeae taraxacifolia normalized blood pressure parameters, urinary sodium, oxidative stress indices, antioxidant defence system, and serum nitric oxide bioavailability.https://www.pjps.pk/homeam2023Paraclinical Science

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.http://www.veterinaryworld.orgdm2022Paraclinical Science

Clofibrate, a peroxisome proliferator–activated receptor-alpha (PPARα) agonist, and Its molecular mechanisms of action against sodium fluoride–induced toxicity

AVAILABILITY OF DATA AND MATERIALS : Data will be made available based on request from the corresponding author.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.Cape Peninsula University of Technology and National Research Foundation (South Africa).https://link.springer.com/journal/12011hj2023Paraclinical Science

Anti-Oxidant, Anti-Inflammatory and Antinociceptive Properties of the Acetone Leaf Extract of Vernonia Amygdalina in Some Laboratory Animals

Purpose: Vernonia amygdalina is a medicinal plant of great importance that has its fresh leaves rich in vitamins and salt hence, it is valuable in human diet. The anti-oxidant, anti-inflammatory and analgesic activities of its acetone leaf extract were evaluated in this study to validate its folkloric use. Methods: The acetone extract is prepared by dissolving ground plant materials (200g) in 1 L of acetone for 48 h, filtered, and then dried using rotary evaporator before it is used for the pharmacological investigations. Standard phytochemical methods were used to test for the presence of phytoactive compounds in the plant. Acute toxicity was carried out in mice to determine safe doses for use. The anti-inflammatory activities were conducted using carrageenan and histamine to induce oedema in rats while analgesic activities were embarked upon using acetic acid- induced writhing test and formalin-induced paw lick test. The anti-oxidant activities were assessed in vitro using ABTS, DPPH, FRAP and total polyphenolics. Results: The results from this study showed that the 100 and 200 mg/kg doses of the acetone extract caused significant reduction in oedema induced by both carrageenan and histamine. Similar effect was observed in analgesic tests which were comparable to that of indomethacin, the reference drug used in the study. Conclusion: The anti-oxidant effects were also good and the pharmacological activities may be due to the presence of polyphenols and other phytochemicals contained in the plant. The study may have thus validated the folkloric use of this plant as a medicinal and nutritional agent

Kolaviron, a biflavonoid of Garcinia kola seed mitigates ischemic/reperfusion injury by modulation of pro-survival and apoptotic signaling pathways

Objective: The study was designed to investigate the ameliorative effect of Kolaviron (KV) on ischemic/ reperfusion injury in experimental animal models. Materials and Methods: Male Wistar rats were randomly divided into two groups: Group 1 received corn oil as a vehicle and rats in Group 2 were administered KV at 200 mg/kg for 4 weeks. The rats were fed with rat standard chow pellet and water administered ad libitum. After 4 weeks of KV administration, hearts were excised and mounted on the working heart perfusion system. Western blot analysis for protein expression was carried out on frozen heart samples. Results: There was significant (P < 0.05) reduction in the activity of catalase, superoxide dismutase, and glutathione peroxidase with concomitant reduction in oxygen radical absorbance capacity in ischemic rat heart of control compared to group pre-treated with KV, respectively. Similarly, intracellular reactive oxygen species and malondialdehyde were significantly elevated in control compared to KV pre-treated rats. KV significantly increased total Akt/protein kinase B (PKB), phosphorylated Akt/PKB at serine 473 and also caused a significant reduction in p38 mitogen-activated protein kinase, Caspase 3, and cleaved poly adenosine diphosphate ribose polymerase. Conclusion: Taken together, KV offered significant cardioprotection via free radical scavenging activity and upregulation of pro-survival pathway.Cape Peninsula University of Technology (CPUT) and University of Ibada

Cobalt chloride-induced oxidant-antioxidant imbalance in rat erythrocytes: The modulatory role of Kolaviron

Cobalt stimulates erythrocyte production via mechanisms that mimic physiological adaptations to hypoxic conditions. However, little is known about alterations in the balance of erythrocyte antioxidant defense system produced by cobalt. We investigated the effect of Kolaviron (KV) on cobalt chloride (CoCl2)-induced disturbances in erythrocyte antioxidant status and hematological parameters and compared the effects with those of Gallic acid (GA). Groups of rats were orally treated with either KV1 (100 mg/kg), KV2 (200 mg/kg) or GA (120 mg/kg), along with CoCl2 (350 ppm) in drinking water for 14 days. CoCl2 produced significant (p&lt;0.05) increases in packed cell volume, hemoglobin and red blood cell count, but no alterations in erythrocyte morphology, in the same way as rats treated with KV or GA. Significant (p&lt;0.05) elevation in malondialdehyde (MDA) content and reductions in total thiols and reduced glutathione (GSH) in the CoCl2 group were indications of oxidative stress. KV produced significant (p&lt;0.05) reduction in MDA, while restoring the levels of GSH and total thiols with elevations in glutathione S-transferase and superoxide dismutase. Our results indicate that CoCl2-induced erythropoiesis was accompanied by altered antioxidant status of the erythrocytes. Kolaviron, however, ameliorated the disturbances in erythrocyte antioxidant defense system

Polyphenol-rich fraction of Parquetina nigrescens mitigates dichlorvos-induced neurotoxicity and apoptosis

Background: Parquetina nigrescens (Afzel.) Bullock of the family Asclepiadaceae is known for its antioxidant effects with wide range of uses in Southwestern Nigeria especially in traditional medicine. This study was undertaken to explore if polyphenol-rich fraction (prf) from P. nigrescens will ameliorate dichlorvos-induced neurotoxicity and apoptosis. The exploration utilized evaluation of markers of oxidative stress, apoptosis and serum acetylcholinesterase (AchE) levels. Methods: Forty Wistar rats randomly placed in four groups were utilized for the study. Animals in Group A received corn oil, group B- dichlorvos (16 mg/kg), groups C and D- dichlorvos + 100 and 200 mg/kg prf of P. nigrescens respectively. Markers of oxidative stress, antioxidants and apoptosis were assessed in the serum and brain tissues using biochemical assay and immunohistochemistry. Results: Exposure to dichlorvos caused significant decreases in AchE, catalase, superoxide dismutase, glutathione peroxidase (GPx) and increases in hydrogen peroxide (H2O2) generation and malondialdehyde levels. Histopathology and immunohistochemistry of the cerebellum and cerebrum of rats exposed to dichlorvos revealed greater neurotoxic effects in the cerebellum as well as decreased expressions of AchE with a concomitant increase in Bax (proapototic) compared to prf of P. nigrescens treated rats. Conclusion: This study showed that dichlorvos caused cellular and tissue neurotoxicity by inhibiting AchE activity, induced oxidative stress and apoptosis in rats with prominent effects on the cerebellum than cerebrum. The prf of P. nigrescens showed amelioration of neurotoxicity by its antioxidative and antiapoptotic properties in rats exposed to dichlorvos