Antioxidant activity enhancement and oxidative damage inhibition by Lagenaria breviflora fruit and Xanthosoma sagittifolium corm in hypertensive Wistar rats.

Cardiovascular diseases are the leading causes of mortality in the world today with hypertension being the major clinical presentation of these diseases. This study assessed the anti-hypertensive effects of Lagenaria breviflora whole fruit and Xanthsoma  sagittifolium corms in experimentally inudced hypertensive Wistar rats. The ability of the plants to ameliorate oxidative damage accompanying hypertension was evaluated using changes in oxidative stress markers as well as monitoring of cardiovascular parameters. Hypertension was induced by intraperitoneal injection of DOCA salt twice weekly and daily inclusion of NaCl (1%) in drinking water. Methanol extracts of L.breviflora or X. sagittifolium was administered to hypertensive rats for 35 days and the outcome was compared to hypertensive rats administred with lisinopril or hydrochlorothiazide and a group of normotensive rats (control). Systolic, diastolic and mean arterial pressures were determined on day 34 and blood sample collected on day 35. The rats were thereafter humanely sacrificed, and organs were harvested. This study showed that the extracts lowered blood pressure, free protein thiols but increased toal protein, gluthathione peroxidase, reduced glutathione, glutathione S-transferase, catalase and nitric oxide in the heart, kidney and liver compared to untreated hypertensive rats. However, malondialdehyde levels and hydrogen peroxide activities were reduced. L. breviflora fruit and X. sagittifloium corm exhibited antihypertensive properties and ameliorate oxidative damage associated with hypertension by enhancing the antioxidant defense sysyem and inhibiting generation of free radicals.

Anti-inflammatory and analgesic effects of methanol extract of red cultivar Allium cepa bulbs in rats and mice.

OBJECTIVES: Several cultivars of Allium cepa L. have been studied for anti-inflammatory and analgesic activities but there is inadequate information on such biological activities of the concentrated extracts of the Nigerian grown red cultivar A. cepa bulb. METHODS: The anti-inflammatory models used in this study were Carrageenan-induced paw oedema and formalin-induced paw lick in rats, while acetic acid-induced abdominal writhing, hot plate reaction, hot water tail flick tests in mice were the analgesic models. RESULTS: At 30 min post-induction (pi), the inhibition of paw oedema (62.50%) by 200 mg/kg of methanol extract of red cultivar A. cepa bulb (MERCACB) was significantly (p<0.001) higher than that of indomethacin (15.63%) at 10 mg/kg. The paw oedema inhibition at 60 min pi by MERCACB (76.92%) was significantly higher than that of indomethacin (41.03%). At the early phase of formalin paw-lick test, the pain reaction time (PRT) of rat treated with MERCACB (400 mg/kg) was significantly lower than that of indomethacin and the control groups. The hotplate test revealed that PRT of mice treated with 800 mg/kg of MERCACB were significantly (p<0.01) longer in comparism to indomethacin and control groups. The PRT of mice subjected to thermal pain due to hot water and treated with 800 mg/kg of MERCACB was significantly (p<0.05) longer than that of the control group. CONCLUSIONS: These findings indicate that MERCACB possesses potent anti-inflammatory and analgesic properties which confirm the traditional use of the plant for the treatment of inflammatory diseases and may be useful as a future therapeutic agent.

Simulation of hemo- and biochemical toxicities associated with chronic inhalation exposure to 2,2-Dichlorovinyl dimethyl phosphate (DDVP) in Wistar rat.

DDVP is a commonly used pesticide in Nigeria and those involved with DDVP manufacturing, packaging or utilizing facilities seldom use PPE to limit pesticide exposure. The study aim was to determine the impact of chronic exposure to DDVP by monitoring hematological and biochemical changes in Wistar rats. Male rats (n = 60; 150-180 g) were exposed to graded DDVP concentrations (0%, 20 %, 40 %, 60 %, 80 % and 100 %) via inhalation route for 60 days. Body weights were initially measured and then at 20-day intervals. Blood samples were collected for hematology and serum biochemistry on day 61. Results showed significant (p < 0.05) polycythemia, neutrophilia, thrombocytosis, hepatic and renal derangement in rats exposed to DDVP. Also, albumin, AST, ALP, creatinine, blood urea nitrogen, bilirubin levels and dyslipidemia significantly increased. Cholinergic signs and stunted growth were observed in higher concentrations. Study emphasized hazards of DDVP mishandling and risks of non-compliance with PPE use by workers in-contact with DDVP, as well as misuse/abuse in animals.

Luteolin-mediated Kim-1/NF-kB/Nrf2 signaling pathways protects sodium fluoride-induced hypertension and cardiovascular complications.

The use of sodium fluoride (NaF) as a major ingredient for tooth paste, mouth wash, and mouth rinse has become inevitable in our day-to-day life. However, flavonoids such as Luteolin might be of great value in the prevention of toxicity associated with accidental or inevitable ingestion of NaF. In the study, 40 male Wistar albino rats were randomly divided into four groups with 10 rats in a group. Group A was the control group and received normal saline, Group B was exposed to NaF at 300 ppm (300 mg/L) in drinking water daily for a week, Groups C and D were exposed to 300 ppm (300 mg/L) of NaF and coadministered with Luteolin orally daily at a dosage of 100 mg/kg and 200 mg/kg for the same time point. Our results indicated that NaF caused significant increases in systolic blood pressure, diastolic blood pressure, mean arterial pressure, malondialdehyde, protein carbonyl, myeloperoxidase, advanced oxidative protein products, together with significant reductions in glutathione peroxidase, superoxide dismutase, catalase, glutathione reductase, reduced glutathione, and nitric oxide (NO) bioavailability. The electrocardiogram results showed that NaF alone caused significant prolongation of QT and QTc intervals. Immunohistochemistry revealed that NaF caused increase expressions of Kidney injury marker 1 (Kim-1), nuclear factor kappa bet (NF-κB), nuclear factor erythroid 2-related factors 2 (Nrf2), and cardiac troponin I (CTnI). Together, Luteolin coadministration with NaF improved NO bioavailability, reduced high blood pressure, markers of oxidative stress, reversed prolongation of QT and QTc intervals, and lowered the expressions of Kim-1, NF-κB, and CTnI. © 2018 BioFactors, 44(6):518-531, 2018.

Ameliorative effect of Rutin on sodium fluoride-induced hypertension through modulation of Kim-1/NF-κB/Nrf2 signaling pathway in rats.

Sodium fluoride is one of the neglected environmental contaminants. Inorganic fluorides in the environment are found in the air, water, and land. In the study, forty-male Wistar albino rats were randomly divided into four groups with 10 rats in a group. Group A was the control group which was given normal saline, Group B was exposed to 300 ppm of NaF in drinking water, while Groups C and D received NaF along Rutin (100 mg/kg and 200 mg/kg) orally daily for a week. Administration of NaF alone led to significant increases in blood pressure, and deceased serum nitric oxide. Immunohistochemistry revealed higher expressions of kidney injury molecule I (Kim-1), nuclear factor kappa beta (NF-κB), and down regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) in rats administered NaF. Rutin co-treatment with NaF normalized blood pressure, lowered Kim-1 and NF-κB expressions, and improved nitric oxide bioavailability.

Telferia Occidentalis and Vitamin C Attenuate Phenylhydrazine-Induced Haemolytic Anaemia and Associated Cardio-renal Dysfunctions via Inhibition of Oxidative Stress and Proapoptotic -Protein (Bax) Expressions.

BACKGROUND: The study investigated the modulatory roles of the aqueous leaf extract of Telferia occidentalis, a traditional haematinic, and vitamin C on cardiovascular dysfunction associated with subchronic Phenylhydrazine exposure. METHODS: Fifty adult male rats were randomly selected and divided into one of five groups of ten animals each: Control; 40 mgkg-1 Phenylhydrazine (PHZ); PHZ with 100 mgkg-1 T.occidentalis; PHZ with 200 mgkg-1 T.occidentalis; and PHZ with 100 mgkg-1 vitamin C. RESULTS: Oral exposure of rats to PHZ, without T. occidentalis or vitamin C treatment, resulted in a significant (p<0.05) decrease in the haematological parameters, but increased the blood pressure parameters of rats However, treatment with vitamin C and T. occidentalis leaf extract significantly (p<0.05) ameliorated the aforementioned PHZ-induced alterations of rats haemogram, and blood pressure. Biochemical analysis revealed significant (p<0.05) reduction in the activities of superoxide dismutase and catalase of untreated PHZ-exposed rats, but the levels of malondialdehyde, hydrogen peroxide and myeloperoxidase of the rats were significantly (p<0.05) increased compared with those of the extract treated rats. Immunohistochemical analysis revealed a greater expression of Bax-protein in the cardiac and renal tissues of the untreated PHZ exposed rats, compared with the extract and vitamin C treated groups. CONCLUSIONS: The mitigation of oxidative stress and inhibition of Bax-protein expression are probable mechanisms of action of T. occidentalis in the amelioration of haemolytic anaemia, and its use as adjunct medication in the management of some diseases is justifiable.

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.

Biochemical and electrocardiographic studies on the beneficial effects of gallic acid in cyclophosphamide-induced cardiorenal dysfunction.

Background Cardiac toxicity is one of the life-threatening complications of cancer therapy. Cyclophosphamide (CYP) is an alkylating agent with potent antineoplastic and immunosuppressive properties and possibly the most widely used antineoplastic agent. Chronic cardiotoxicity associated with CYP is characterized by progressive heart failure developing from weeks to years after therapy. Methods In this study, rats were administered with (60 mg/kg and 120 mg/kg) alone or in combination with single intraperitoneal (200 mg/kg) administration of CYP for 7 days. CYP was only administered on day 1. Results The administration of CYP led to a significant (p<0.05) increase in cardiac and renal malondialdehyde (MDA) contents and hydrogen peroxide (H2O2) generation. Also, the activities of catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) levels were significantly (p<0.05) reduced following CYP treatment. A significant (p<0.05) increase in serum myeloperoxidase (MPO) activity was recorded in rats administered CYP only. Electrocardiogram (ECG) showed a significant (p<0.05) increase in heart rate (HR) accompanied by transient decrease in QRS duration. Histologic examination revealed architectural anarchy of both heart and kidney of rats that received only CYP. Conclusions In this study, treatment with gallic acid (60 mg/kg and 120 mg/kg) restored the enzymic and non-enzymic antioxidants and also attenuated cardiotoxic and nephrotoxic effect of CYP through free radical scavenging activity, anti-inflammatory and improvement of antioxidant defence system.

Cyclophosphamide-induced Hepatotoxicity in Wistar Rats: The Modulatory Role of Gallic Acid as a Hepatoprotective and Chemopreventive Phytochemical.

BACKGROUND: Gallic acid (GA) is an endogenous plant phenol known to have antioxidant, free radical scavenging ability, anti-inflammatory, anti-cancer, and anti-fungal properties. The aim of this study was to assess the protective effect of GA on cyclophosphamide (CPA)-induced hepatotoxicity in male Wistar rats. METHODS: Sixty rats were grouped into six groups of 10 rats per group. Group 1 received distilled water. Group 2 received CPA at 200 mg/kg single dose intraperitoneally on day 1. Groups 3 and 4 received a single dose of CPA (200 mg/kg) intraperitoneally on day 1 and then were treated with GA at 60 and 120 mg/kg body weight for 14 days, respectively. Rats in Groups 5 and 6 only received GA at 60 and 120 mg/kg body weight for 14 days, respectively. GA was administered orally. RESULTS: CPA induced hepatic damage as indicated by significant elevation (P < 0.05) in aspartate aminotransferase, organ weight, and evidence by the histological study. CPA also induced hepatic oxidative stress as indicated by significant elevation (P < 0.05) in malondialdehyde content, hydrogen peroxide (H2O2) generation, nitrite level, and the level of glutathione (GSH) peroxidase crashed in the CPA-treated group. GA enhanced the antioxidant defense system as indicated by significant elevation (P < 0.05) in GSH level, catalase activity, and GSH-S-transferase activity. CONCLUSIONS: Taken together, the result of this present study shows that GA has a protective effect on CPA-induced hepatotoxicity.

Gallic Acid Ameliorates Cyclophosphamide-Induced Neurotoxicity in Wistar Rats Through Free Radical Scavenging Activity and Improvement in Antioxidant Defense System.

Cyclophosphamide (CPA) is a widely used anticancer chemotherapeutic agent and its toxicity has been associated with its toxic metabolites phosphormide mustard. Therefore, the ameliorative effect of Gallic acid against neurotoxicity was examined in this study. Sixty rats were grouped into 10 rats per group. Group 1 received saline orally. Group 2 received CPA at 100 mg/kg single dose intraperitoneally on day 1. Groups 3 and 4 were treated with Gallic acid (GA) at 60 and 120 mg/kg body weight only for 10 days and also received a single dose of CPA (100 mg/kg) intraperitoneally on day 1, respectively. Rats in groups 5 and 6 received GA at 60 and 120 mg/kg body weight only for 10 days. Groups 3, 4, 5, and 6 received GA orally. The cerebellar and cerebral malondialdehyde (MDA) contents and hydrogen peroxide generation were significantly (p < .05) elevated. The cerebellar and cerebral catalase (CAT), superoxide dismutase and glutathione-S-transferase (GST) activities were significantly (p < .05) reduced in CPA treated group. The activity of glutathione peroxidase (GPx) was significantly increased in rats that were treatment with CPA. Also, nitrite content was significantly elevated in the brain of rats that received the toxic dose of CPA. All these findings suggest that treatment with GA (60 and 120 mg/kg) ameliorated the neurotoxicity induced by CPA via reduction of oxidative stress and increase in antioxidant defense system. Combining all, chemotherapeutic agents with structure/function similar to GA could be of potential benefit to the pharmaceutical industries as an adjuvant in chemotherapy with little or no side effects.

Lack of reversal of oxidative damage in renal tissues of lead acetate-treated rats.

Removal of lead from the environment of man or otherwise, the movement of man from lead-contaminated areas has been employed as a means of abatement of the toxic effects of lead. Whether toxic effects in already-exposed individuals subside after lead withdrawal remains unanswered. To understand the reversibility of nephrotoxicity induced by lead acetate, male Wistar rats were orally exposed to 0.25, 0.5, and 1.0 mg/mL of lead acetate for 6 weeks. Activities of glutathione-s-transferase, catalase (CAT), superoxide dismutase (SOD) and the concentrations of hydrogen peroxide (H2 O2 ), and malondialdehyde increased significantly (p < 0.05) in a dose-dependent manner, whereas reduced glutathione (GSH) level and glutathione peroxidase activity were significantly reduced. The pattern of alterations in most of the oxidative stress and antioxidant parameters remained similar in rats from the withdrawal period, although CAT and SOD activities reduced, in contrast to their elevation during the exposure period. Serum creatinine levels were significantly elevated in both exposure and withdrawal experiments whereas serum blood urea nitrogen levels were not significantly different from the control in both exposure and withdrawal periods. The histological damage observed include multifocal areas of inflammation, disseminated tubular necrosis, and fatty infiltration of the kidney tubules both at exposure and withdrawal periods. The results suggest that lead acetate-induced nephrotoxicity by induction of oxidative stress and disruption of antioxidant. The aforementioned alterations were not reversed in the rats left to recover within the time course of study.

Studies on the anti-inflammatory, analgesic and antipyrexic activities of betulinic acid derived from Tetracera potatoria.

BACKGROUND: The anti-inflammatory and anti-nociceptive activity of betulinic acid (BA) was investigated in this study. The triterpene was isolated from the ethyl acetate extract of Tetracera potatoria and its structure was verified by IR and NMR spectroscopy. The bioactivity of this compound was assessed using carrageenan-induced paw oedema in rats and carrageenan-induced pulmonary oedema in mice for the anti-inflammatory activity, while acetic acid-induced writhing test in mice and zymosan-induced fever in rats were used for analgesic test. MATERIALS AND METHODS: Rats and mice were randomly divided into groups of five animals. For each experiment, betulinic acid at 10, 20 or 40mg/kg b.w was administered intraperitoneally to the first three groups respectively. The fourth group was administered with indomethacin (10mg/kg) or acetylsalicylic acid (150mg/kg), while the fifth group was administered with distilled water (10ml/kg). Data obtained were expressed as mean±S.E.M and significant differences were determined at p<0.05. RESULTS: BA significantly reduced carrageenan-induced paw oedema by 11.0%, 45.7%, 68.6% or pulmonary oedema by 25.6, 29.2 and 45.13% dose dependently. 40 mg/kg of BA inhibited paw oedema by 68.6% comparably to acetylsalicylic acid (71.4%) or indomethacin (51.33%) respectively. Abdominal writhing was also significantly (p<0.05) reduced to 17.20 writhes by BA (40mg/kg) comparable to Indomethacin (16.3writhes). Fever was inhibited by BA most significantly by 3hours post-injection of zymosan (1.00, 1.45, 0.00°C) and this inhibitory effect was higher than that observed for acetylsalicylic acid (0.30°C). CONCLUSION: Betulinic acid derived from Tetracera potatoria exhibited potent anti-inflammatory, analgesic or antipyrexic activity which is comparable to indomethacin or acetylsalicyclic acid.