L-arginine and lisinopril supplementation protects against sodium fluoride-induced nephrotoxicity and hypertension by suppressing mineralocorticoid receptor and angiotensin-converting enzyme 3 activity.

Sodium fluoride (NaF) is one of the neglected environmental toxicants that has continued to silently cause toxicity to both humans and animals. NaF is universally present in water, soil, and atmosphere. The persistent and alarming rate of increase in cardiovascular and renal diseases caused by chemicals such as NaF in mammalian tissues has led to the use of various drugs for the treatment of these diseases. The present study aimed at evaluating the renoprotective and antihypertensive effects of L-arginine against NaF-induced nephrotoxicity. Thirty male Wistar rats (150-180 g) were used in this study. The rats were randomly divided into five groups of six rats each as follows: Control, NaF (300 ppm), NaF + L-arginine (100 mg/kg), NaF + L-arginine (200 mg/kg), and NaF + lisinopril (10 mg/kg). Histopathological examination and immunohistochemistry of renal angiotensin-converting enzyme (ACE) and mineralocorticoid receptor (MCR) were performed. Markers of renal damage, oxidative stress, antioxidant defense system, and blood pressure parameters were determined. L-arginine and lisinopril significantly (P < 0.05) ameliorated the hypertensive effects of NaF. The systolic, diastolic, and mean arterial blood pressure of the treated groups were significantly (P < 0.05) reduced compared with the hypertensive group. This finding was concurrent with significantly increased serum bioavailability of nitric oxide in the hypertensive rats treated with L-arginine and lisinopril. Also, there was a significant reduction in the level of blood urea nitrogen and creatinine of hypertensive rats treated with L-arginine and lisinopril. There was a significant (P < 0.05) reduction in markers of oxidative stress such as malondialdehyde and protein carbonyl and concurrent increase in the levels of antioxidant enzymes in the kidney of hypertensive rats treated with L-arginine and lisinopril. The results of this study suggest that L-arginine and lisinopril normalized blood pressure, reduced oxidative stress, and the expression of renal ACE and mineralocorticoid receptor, and improved nitric oxide production. Thus, L-arginine holds promise as a potential therapy against hypertension and renal damage.

Supplementation of antihypertensive drug regimen with vitamin E ameliorates alterations of primary haemodynamic parameters and total antioxidant capacity in ovariectomised rats.

OBJECTIVES: Ovariectomy induces heightened response to vasoconstrictors, alters vasorelaxation and consequently causes hypertension due to increased oxidative stress in rats. METHODS: This study evaluated the ameliorative effects of ramipril and vitamin E, on primary haemodynamic parameters and cardiac antioxidant defence status, in ovariectomised rats using 64 adult female rats of the Wistar strain randomly divided as follows: Control (sham); Ovariectomised (OVX); OVX plus Ramipril; OVX plus vitamin E; and OVX plus Ramipril plus vitamin E. RESULTS: The plasma level of oestrogen was significantly lower (p<0.05), in the ovariectomised rats compared with the sham. The systolic, diastolic and mean arterial blood pressure of ovariectomised rats increased significantly (p<0.05), but the alteration was significantly reduced by the administration of ramipril alone or in combination with vitamin E. Significant decrease (p<0.05) was observed in the serum level of nitric oxide in OVX group compared with Sham. Also, analysed markers of oxidative stress: Malondialdehyde (MDA) contents and hydrogen peroxide (H2O2) generated decreased significantly (p<0.05), but systemic antioxidants: reduced glutathione (GSH) contents; glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities increased significantly (p<0.05) in the ovariectomised rats treated with ramipril and vitamin E compared with untreated ovariectomised rats. The study concludes that alteration, in the primary haemodynamic parameters, associated with ovariectomy in rats is potently ameliorated by co-administration of the antihypertensive drug ramipril and vitamin E. CONCLUSIONS: The supplementation of antihypertensive regimen with antioxidants such as vitamin E in the treatment of hypertension is therefore justifiable especially in ovariectomised or hypogonadal patients.

Infused aqueous curry tea extracts ameliorate Nω -Nitro-L-Arginine Methyl Ester-induced liver dysfunction in male albino Wistar rats.

BACKGROUND: Murraya koenigii (L.) Spreng. (Rutaceae) has been reported to positively affect liver function. However, the effect of M. koenigii leaves on Nω -Nitro-L-Arginine Methyl Ester (L-NAME) induced liver dysfunction is unknown. The aim of the present study was therefore to investigate the effect of M.koenigii leaves as tea on L-NAME induced liver dysfunction. METHODS: Two variants of curry tea were formulated; one was formulated entirely from leaves of M. koenigii, the other was formulated with thaumatin-rich aril obtained from seeds of Thaumatococcus danielii (Benn.) Benth. (Marantaceae). Group I animals served as control and were untreated. Groups II and V animals were administered curry tea (CT). Group III and VI animals received curry-thaumatin tea (CTT). Concurrently, L-NAME (40 mg/kg) was administered to groups IV-VI respectively for 21 days. Blood and liver samples were collected at the end of the study for biochemical, histological, and immunohistochemical analysis. RESULTS: L-NAME induced liver dysfunction evidenced by liver histology, increased activities of ALT, AST, hyperlipidemia, hepatic oxidative stress and increased hepatic NF-kB expression. Administration of CT and CTT ameliorated the L-NAME induced liver dysfunction evidenced by liver histology, increased NO hepatic bioavailability, reduced activity of ALT and AST, increased hepatic antioxidant system and decreased hepatic NF-kB expression. Thaumatin taste/flavor enhancer did not significantly reduce or potentiate the hepatoprotective, antioxidant and anti-lipidemic property of aqueous curry tea extracts in rats. CONCLUSION: L-NAME impaired liver function in rats. CT and CTT interfered with the ability of L-NAME to inhibit NO synthesis which was associated with ameliorated hepatic dysfunction. PRACTICAL APPLICATIONS: The study reports that non-selective inhibition of nitric oxide by L-NAME in rats impairs liver function and formulated curry tea types interfered with the ability of L-NAME to inhibit NO synthesis which was associated with ameliorated hepatic dysfunction in rats.

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 100mg/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 In-vivo 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.

Compensatory depression of arterial pressure and reversal of ECG abnormalities by Annona muricata and Curcuma longa in hypertensive Wistar rats.

OBJECTIVES: Increasing hypertension incidence in Sub-Sahara Africa and the current cost of management of the metabolic disorder has necessitated research on medicinal plants employed in African Traditional Medicine for hypertension. Thus, this study evaluated antihypertensive effect of Annona muricata leaves or Curcuma longa rhizomes in experimentally-induced hypertensive male Wistar rats (n=70) which were unilaterally nephrectomized and daily loaded with 1% salt. Cardiovascular and haematological changes, as well as urinalysis were determined. METHODS: Rats were uninephrectomized and NaCl (1%) included in drinking water for 42 days. Extract-treated hypertensive rats were compared to normotensive, untreated hypertensive and hypertensive rats treated with lisinopril (5 mg/70 kg) or hydrochlorothiazide (12.5 mg/70 kg). A. muricata extract or C. longa extract were administered at 100, 200 or 400 mg/kg. Blood pressure (systolic, diastolic and mean arterial) and electrocardiogram was measured on day 41. Twenty-four-hour urine samples were collected from day 42. Blood samples were collected on day 43 for haematology (PCV, red cell indices, WBC and its differentials, and platelets). RESULTS: A. muricata or C. longa extracts caused a decline in elevated blood pressure of hypertensive rats. Heart rate and QT segment reduction coupled with prolonged QRS duration were reversed in extract-treated rats, with significant increases in hemogram parameters indicating increased blood viscosity. Also, leukocyturia, proteinuria and ketonuria with increased urine alkalinity, urobilinogen and specific gravity which are classical indicators of poor prognostic outcomes in hypertension were reversed in extract-treated rats. CONCLUSIONS: In conclusion, A. muricata and C. longa have cardioprotective effect with reversal of derangements in haemogram and urinalysis associated with hypertension.

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.

Novel antihypertensive action of rutin is mediated via inhibition of angiotensin converting enzyme/mineralocorticoid receptor/angiotensin 2 type 1 receptor (ATR1) signaling pathways in uninephrectomized hypertensive rats.

Hypertension is the most common cardiovascular disease that affects approximately 26% of adult population, worldwide. Rutin is one of the important flavonoids that is consumed in the daily diet, and found in many food items, vegetables, and beverages. Uninephrectomy (UNX) of the left kidney was performed, followed by induction of hypertension. The rats were randomly divided into four groups of 10 rats: group 1-Sham-operated rats; group 2-UNX rats, group 3-UNX-L-NAME (40 mg/kg) plus rutin (100 mg/kg bwt), and groups 4-UNX-L-NAME plus lisinopril (10 mg/kg bwt), orally for 3 weeks. Results revealed significant heightening of arterial pressure and oxidative stress indices, while hypertensive rats treated with rutin had lower expressions of angiotensin converting enzyme (ACE) and mineralocorticoid receptor in uninephrectomized rats. Together, rutin as a novel antihypertensive flavonoid could provide an unimaginable benefits for the management of hypertension through inhibition of angiotensin converting enzyme and mineralocorticoid receptor. PRACTICAL APPLICATIONS: Hypertension has been reported to be the most common cardiovascular disease, affecting approximately 26% of the adult population worldwide with predicted prevalence to increase by 60% by 2025. Recent advances in phytomedicine have shown flavonoids to be very helpful in the treatment of many diseases. Flavonoids have been used in the treatment and management of cardiovascular diseases, obesity and hypertension. The study revealed that rutin, a known flavonoid inhibited angiotensin converting enzyme (ACE), angiotensin 2 type 1 receptor (ATR1), and mineralocorticoid receptor (MCR), comparable to the classic ACE inhibitor, Lisinopril, indicating the novel antihypertensive property of rutin. Therefore, flavonoids such as rutin found in fruits and vegetables could, therefore, serve as an antihypertensive drug regimen. Combining all, functional foods rich in flavonoids could be used as potential therapeutic candidates for managing uninephrectomized hypertensive patients.

Luteolin supplementation ameliorates cobalt-induced oxidative stress and inflammation by suppressing NF-кB/Kim-1 signaling in the heart and kidney of rats.

Cobalt-induced cardiomyopathy and renal toxicity have been reported in workers in processing plants, hard metal industries, diamond polishing and manufacture of ceramics. This study was designed to investigate the influence of Luteolin supplementation on cobalt-induced cardiac and renal toxicity in rats. Exposure of rats to cobalt chloride (CoCl2) alone caused significant (p < 0.05) increases in cardiac and renal H2O2, malondialdehyde (MDA) and nitric oxide (NO), along with increased serum myeloperoxidase (MPO) activity. In addition, there were significant (p < 0.05) reductions in cardiac and renal glutathione peroxidase (GPx), glutathione S-transferase (GST) and reduced glutathione (GSH). CoCl2 induced higher immuno-staining of nuclear factor kappa beta (NF-κB) in the heart and kidneys, and the kidney injury molecule (Kim-1) in the kidneys. Treatment with Luteolin or Gallic acid produced significant reversal of the oxidative stress parameters with reductions in NF-κB and Kim-1 expressions, leading to suppression of histopathological lesions observed in the tissues.

Methanol extract of Caesalpinia benthamiana normalizes blood pressure and attenuates oxidative stress in uninephrectomized hypertensive rats.

OBJECTIVES: Hypertension is the number one risk factor and primary contributor of cardiovascular diseases. Caesalpinia benthamiana is a valuable medicinal plant with unvalidated anti-hypertensive activity. This study was carried out to explore the antihypertensive effect of C. benthamiana on uninephrectomized hypertensive rats. METHODS: Fifty rats were grouped into five groups, each containing 10 animals: Group A-normal control (normotensive); B-uninephrectomized control; C-uninephrectomized treated with 50 mg/kg C. benthamiana extract; D-uninephrectomized treated with 100 mg/kg C. benthamiana; and E- uninephrectomized treated with 10 mg/kg of Lisinopril. RESULTS: Significant increases were observed in systolic, diastolic and mean blood pressure of uninephrectomized control rats. Furthermore, markers of oxidative stress (malondialdehyde, hydrogen peroxide, protein carbonyl, myeloperoxidase and the advanced oxidative protein products) increased significantly while antioxidant status (reduced glutathione, glutathione peroxidase, glutathione S-transferase and superoxide dismutase), reduced significantly in uninephrectomized hypertensive rats. Histopathology revealed thrombosis and occlusion of coronary vessels in the heart, and congestion in the kidney. However, the observed high blood pressure parameters were remarkably normalized together with reduction in markers of oxidative stress and improvement in antioxidant defence system of uninephrectomized hypertensive rats treated with C. benthamiana extract similar to normotensive rats. CONCLUSIONS: C. benthamiana extract exhibited antihypertensive action, strong antioxidant ability, attenuated oxidative stress-mediated hypertension and lessened the development of cardiac and renal damage associated with hypertension induced by uninephrectomy and high dietary intake of salt. Together, C. benthamiana extract might be useful in the management of hypertension due to volume overload in the cardiovascular system.

Antihypertensive effect of Phragmanthera incana (Schum) Balle on NG-nitro-L-Arginine methyl ester (L-NAME) induced hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Phragmanthera incana (Schum) Balle is a member of the African mistletoes that has been reported to be used in ethnomedicine for the treatment of hypertension. AIM: The aim of this study was to investigate the antihypertensive effect of Phragmanthera incana leaf ethanol extract (PILEE) in NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. MATERIALS AND METHODS: Phytochemical analysis of PILEE was determined using the Gas chromatography - Mass spectrophotometry (GC-MS) method. Antihypertensive activity was investigated in rats that received PILEE (50, 100 and 200 mg/kg) or captopril (40 mg/kg) daily for 28 days together with oral administration of L-NAME (40 mg/kg). Blood pressure parameters were measured on day 7, 14, 21 and 28. Blood was obtained for determination of serum nitrite, interleukin-6 (IL-6) and tumor necrosis factor, TNF-α. The heart, liver and kidneys were used to determine oxidative stress indices (malondialdehyde, reduced glutathione and catalase). The cardiac tissue was processed for histopathological changes. RESULTS: The GC-MS profiling of PILEE identified 20 compounds namely fatty acid esters. Administration of PILEE (50, 100 and 200 mg/kg) dose dependently and significantly reduced systolic blood pressure and mean arterial pressure in hypertensive rats. PILEE administration significantly (p < 0.05) reversed elevated IL-6 and TNF-α in hypertensive rats. PILEE demonstrated antioxidant activity by attenuating L-NAME-induced elevated malondialdehyde and depletion of reduced glutathione and catalase activity in rat tissues. PILEE treatment demonstrated cardioprotective effect in L-NAME-induced cardiac hyperplasia and necrosis in rats. CONCLUSION: It can be concluded that Phragmanthera incana leaf ethanol extract possess antihypertensive, antioxidant and anti-inflammatory properties, suggesting a protective role in cardiovascular diseases.

Anti-lipidemic Effect of Fractions of Peristrophe bivalvis Leaf in NG-nitro-L-arginine Methyl Ester (L-NAME) Treated Rats.

PURPOSE: The reduction in nitric oxide (NO) bioavailability accelerates atherosclerosis development, augments lipolysis, elevates blood pressure and upregulate leukocyte level. This study was designed to examine the biochemical constituents of fractions of Peristrophe bivalvis (PB) leaf, their effect on blood pressure, serum lipid contents and complete blood count in NG-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. METHOD: Male Wistar rats were grouped into control and hypertensive groups. The hypertensive group was pretreated with 60 mg/kg b.w of L-NAME (L-NAME60) daily for two weeks. They were then randomly sub-grouped into: Hypertensive (H), Hypertensive+n-hexane fraction (HHF), Hypertensive+dichloromethane fraction (HDF), Hypertensive+ethyl acetate fraction (HEF) and Hypertensive+aqueous fraction (HAF) groups. These were orally gavaged with L-NAME60 and L-NAME60+200 mg/kg b.w of fractions of PB respectively, daily for two weeks. RESULT: The biochemical components analysis of the fractions of PB identified numerous polar and non polar compounds like alkaloids, organic acids and esters. The results showed a significant increase in NO level in HHF and HEF groups compared to H. Total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C) and very LDL-C were significantly decreased in HAF group compared to H. High density lipoprotein cholesterol (HDL-C) increased significantly and atherogenic indices decreased significantly in HHF, HDF and HAF groups compared to H, while reduced glutathione level increased significantly in HHF group compared to H. White blood cells count effectively decreased in HEF group compared to H. CONCLUSION: In brief, the fractions of PB leaf increased HDL-C and NO, and decrease atherogenic indices in L-NAME treated rats.

Ameliorative effects of Annona muricata Linn. (Annonaceae) against potassium dichromate-induced hypertension in vivo: involvement of Kim-1/p38 MAPK/Nrf2 signaling.

Background Recently, the incidences of hypertension and environmental pollution have increased significantly. This study investigates the antihypertensive effect of Annona muricata extract against K2Cr2O7-induced hypertension. Methods Fifty rats were used for this study, which were divided into five groups of 10 rats each. Rats in Group A received normal saline, and those in Groups B, C, D, and E were treated with A. muricata extract alone at 250 mg/kg, K2Cr2O7 at 30 mg/kg, pretreated with the extract at 250 mg/kg, and pretreated with gallic acid at 60 mg/kg for 14 days, respectively, and thereafter administered with a single intraperitoneal injection of K2Cr2O7 at 30 mg/kg. Results Administration of K2Cr2O7 significantly increased systolic, diastolic, and mean arterial pressure and caused prolonged QT and QTc intervals. Further, pretreatment with the extract at 250 mg/kg and gallic acid at 60 mg/kg significantly reduced high blood pressure to near-normal values. K2Cr2O7 intoxication led to significant increases in serum advanced oxidative protein products, myeloperoxidase, and xanthine oxidase, while serum nitric oxide (NO) also reduced significantly. Immunohistochemistry of the renal kidney injury molecule (Kim-1) and p38 MAPK showed increased expressions following the administration of K2Cr2O7 together with the downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2). Pretreatment with the extract at 250 mg/kg and gallic acid at 60 mg/kg also increased the expressions of Nrf2 and downregulated Kim-1 and p38. Conclusion Together, we found that pretreatment with the extract at 250 mg/kg and gallic acid at 60 mg/kg normalized the blood pressure, reduced the markers of oxidative stress, and improved the antioxidant defense system and serum NO bioavailability.

Antihypertensive Effect of Polyphenol-Rich Fraction of Azadirachta indica on Nω-Nitro-L-Arginine Methyl Ester-Induced Hypertension and Cardiorenal Dysfunction.

Azadirachta indica (AI) is a medicinal plant with reported antioxidant and cardio-protective properties. The use of plant-based polyphenols has become greatly increased in the last one decade. The present study investigated the protective effect of the polyphenol-rich fraction (PRF) of the methanol-extract of Azadirachta indica against Nω-Nitro-L-Arginine Methyl Ester (L-NAME) induced hypertension and cardiorenal dysfunction in rats. Fifty (50) Wistar albino rats were grouped into five groups. Group A, the control, was administered potable water. Groups B-E received orally, 40 mg/kg of L-NAME only, 40 mg/kg of L-NAME and 100 mg/kg of AI extract, 40 mg/kg of L-NAME and 200 mg/kg of AI extract, and 40 mg/kg of L-NAME and 25 mg/kg of captopril, respectively for 21 days. The results of the present study revealed that L-NAME administration led to a significant increase in systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure. Markers of oxidative stress (malondialdehyde,protein carbonyl) increased significantly while there was reduction in reduced glutathione level, activities of superoxide dismutase, glutathione peroxidase and glutathione-S-transferase as well nitric oxide bioavailability. Immunohistochemistry revealed higher expressions of nuclear factor kappa beta (NF-kB) and kidney injury molecule 1(Kim-1) and lower expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) in hypertensive rats. Our results indicated that with PRF of AI restored high blood pressure, reduced markers of oxidative stress, normalized serum NO bioavailability and increased the expressions of Nrf2. Hence, PRF of Azadirachta indica could be used for the treatment of hypertension.

Nephroprotective properties of the methanol stem extract of Abrus precatorius on gentamicin-induced renal damage in rats.

Background The use of plants for the treatment and prevention of diseases in man and his animals has led to a renewed scientific interest in the use of medicinal plants for therapeutic purposes. The nephroprotective properties of methanol stem bark extract of Abrus precatorius against gentamicin-induced renal damage in rats was evaluated in this study. Methods Thirty male Wistar rats were divided into five equal groups. Group A was the negative control group while B was the positive control group which received gentamicin 100 mg/kg intra-peritoneally for 6 days. Group C were pretreated with 100 mg/kg extract for the 3 days and then concurrently with gentamicin 100 mg/kg for 3 days and group D were pretreated with 200 mg/kg extract for 3 days and then concurrently with gentamicin 100 mg/kg for 3 days. Group E received gentamicin intraperitoneally for 6 days followed by administration of 200 mg/kg of the extract for 3 days. Blood samples, kidneys and kidney homogenates were collected for haematological, biochemical, histopathological and immunohistochemical analysis. Results The results showed that no significant haematological changes were noted. The groups treated with extract exhibited significant increase in body weight gain. While group B significantly exhibited focal areas of inflammation, fatty degeneration, congestion of vessels, tubular necrosis and glomerular atrophy, the lesions were mild with the treated groups. Treated groups exhibited a dose dependent significant decrease in serum creatinine, urea, XO, NO and Myeloperoxidase, AOPP, Protein carbonyl, H2O2 generated and MDA levels when compared with group B. There were significant dose dependent improvements in SOD, GST, GSH, Protein thiol, and non-protein thiol levels in the treated groups when compared with group B. In immunohistochemistry, Group B exhibited over expression of CRP and NF-κB levels, and marked reduction in expression of Bcl-2 while the reverse was seen in the groups treated with methanol extracts of Abrus precatorius. Conclusion The methanol extract of Abrus precatorius plays a vital role against gentamicin induced renal damage by reducing levels of renal markers of oxidative stress, inflammation and apoptosis, enhancing enzymatic and non enzymatic renal antioxidant system, alongside an increase in Bcl-2 and a decrease in NF-κB and CRP expressions.

Kolaviron attenuated arsenic acid induced-cardiorenal dysfunction via regulation of ROS, C-reactive proteins (CRP), cardiac troponin I (CTnI) and BCL2.

Arsenic acid is one of the abundant environmental pollutants present in soil, water and the air. Undoubtedly, it has found its way to the food chain in which humans and animals are the final targets thereby causing arrays of disease conditions including cardiovascular and renal dysfunction. Hence, the use of phytochemicals present in medicinal plants has gained global acceptance as chemotherapeutic agents that can prevent, ameliorate, reverse or treat diseases. From our study, arsenic acid intoxication led to significant increase in heart rate (HR), QRS, together with prolonged QT and QTc interval. However, Kolaviron (KV) at the dosage of 100 and 200 mg/kg body weight reversed the aforementioned electrocardiographic (ECG) changes. KV pre-treatment also ameliorated cardiorenal dysfunction via significant reduction in cardiac and renal markers of oxidative stress such as malondialdehyde, hydrogen peroxide generation, myeloperoxidase activity and nitric oxide contents. Immunohistochemistry revealed expressions of renal C-reactive proteins (CRP) and expressions of anti-apoptotic protein BCL2 in KV treated rats. Furthermore, cardiac troponin I (CTnI) expressions were lower in KV treated rats. Taken together, KV mitigated arsenic-acid induced cardiovascular dysfunction via up-regulation of antioxidant defense system and down-regulation of inflammatory and apoptotic signaling pathways.

The Protective Effect of the Ethanol Leaf Extract of Andrographis Paniculata on Cisplatin-Induced Acute Kidney Injury in Rats Through nrf2/KIM-1 Signalling Pathway.

The ethanol leaf extract of Andrographis paniculata was used to ameliorate the renal toxicity induced by cisplatin in 28 rats divided into four groups of seven rats per group. Group A received normal saline for the duration of the experiment. Group B animals were treated with cisplatin (10 mg/kg i.p) on day 1 and 3 days after received normal saline for the next 7 days while groups C and D animals also received 10 mg/kg dose of cisplatin on day 1 but after 3 days were then respectively treated with 200 and 400 mg/kg doses of the extract of Andrographis paniculata for the remaining 7 days through oral administration. Serum chemistry was used for the determination of markers of oxidative stress, anti-oxidant enzymes, serum biomarkers etc. Histopathology and immunohistochemistry were also carried out. Results showed that all oxidative stress markers assayed were significantly increased in group B animals but reverse is the case for groups C and D. On the other hand, antioxidant enzymes assayed experienced significant increase for groups C and D while these parameters experienced significant decrease for group B animals. Histopathology showed severe infiltration of inflammatory cells into renal tissues of group B animals whereas for groups C and D animals, only moderate glomerular degeneration was noted. In immunohistochemistry, while there is higher expression of KIM-1 for group B, there was a lower expression in groups C and D. Again, there was lower expression of Nrf2 for group B but higher expressions in groups C and D animals.

Protective Effect of Azadirachta indica and Vitamin E Against Arsenic Acid-Induced Genotoxicity and Apoptosis in Rats.

Sodium arsenite (NaAsO2) is one of the major environmental toxicants with severe toxicological consequences in some developing and developed countries. Rats in Group A received normal saline. Genotoxicity and apoptosis were induced by single intraperitoneal injection of 10 mg/kg sodium arsenite to rats in Groups B-F. Rats in Groups C and D had earlier been pretreated with Azadirachta indica (100 and 200 mg/kg) or E and F with vitamin E (50 and 100 mg/kg), respectively. Markers of oxidative stress, inflammation, hepatic damage, genotoxicity, and apoptosis were assessed. Pretreatment of rats with either Azadirachta indica or vitamin E led to a significant (p <.05) increase in the activities of glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) in the liver compared to the group that received NaAsO2 alone. Markers of oxidative stress and inflammation, malondialdehyde (MDA), hydrogen peroxide (H2O2) generation, nitric oxide (NO), and myeloperoxidase (MPO), were significantly (p <.05) lowered in rats pretreated with Azadirachta indica or vitamin E. The frequency of micronucleated polychromatic erythrocytes (MNPCEs) and expression of caspase-3 were significantly (p <.05) reduced in rats pretreated with either Azadirachta indica or vitamin E compared to rats intoxicated with arsenite. Histopathology of the liver showed areas of infiltration of inflammatory cells with deaths of numerous hepatocytes in NaAsO2-intoxicated rats, and these were reversed by Azadirachta indica. Together, we report for the first time the genoprotective and antiapoptotic effect of Azadirachta indica by a significant reduction in the frequency of micronuclei-induced apoptosis and oxidative stress by arsenic intoxication.

Ameliorative effect of Azadirachta indica on sodium fluoride-induced hypertension through improvement of antioxidant defence system and upregulation of extracellular signal regulated kinase 1/2 signaling.

BACKGROUND: Toxicities due to fluoride exposure from natural and industrial sources occur commonly in man and animals with severe consequences ranging from mild cardiac derangements to sudden death. In this study, we investigated the protective effects of the methanol extract of Azadirachta indica (AI) against sodium fluoride (NaF)-induced hypertension and genotoxicity in rats. METHODS: Sixty rats were divided into six groups of ten rats each as follows: Group A, the control group received distilled water; Group B rats were administered NaF at 600 ppm in drinking water; Groups C and D rats were pre-treated with the methanol extract of AI and thereafter administered NaF at 600 ppm in drinking water for 7 consecutive days; Groups E and F rats were co-administered with AI and NaF. RESULTS: The administration of NaF caused significant (p<0.05) increases in the blood pressure, markers of oxidative stress, serum myeloperoxidase, xanthine oxidase values in NaF-alone treated rats, compared with the control. Significant (p<0.05) decreases were observed in cardiac and renal antioxidant defence system in rats administered NaF alone compared with the control group. NaF treatment also resulted in a reduction in the expressions of extracellular signal-regulated kinase (ERK) 1/2 in cardiac and renal tissues of NaF-treated rats. Moreover, NaF treatment elicited an increase in the frequency of micronucleated polychromatic erythrocytes when compared with the control group. CONCLUSIONS: This study shows the protective effect of AI on NaF-induced hypertension and genotoxicity through antioxidant and ERK 1/2 signaling in rats.

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.

The aqueous tuber extract of Pueraria tuberosa (Willd.) D.C. caused cytotoxic effect on HT 29 cell lines with down regulation of nuclear factor-kappa B (NF-κB).

Background Pueraria tuberosa (Willd) D.C. (Fabaceae) tubers are already used in traditional medicine by Ayurvedic physicians for the management of fertility disorders, general weakness, and also as anti-ageing therapies. Other known pharmacological properties include: anti-hyperglycemics, hepatoprotective, anti-hyperlipidemic, diuretic, nutritive, and anti-fertility agents in male rats. Methods The anti-proliferative effect of the aqueous tuberous root extract of Pueraria tuberosa on vascular smooth muscle cells (VSMCs) and Human Colorectal Adenocarcinoma Cell lines (HT-29) was investigated using the Cell Titer 96 MTT Proliferation Assay where the viable cells were seeded at a density of 5 × 104 (100 µL/well). For VSMC, log concentrations of the extract at 200 and 800 µg/mL were added and incubated for 24 and 48 h time points. Incubation of the extract in the presence of vascular endothelial growth factor (VEGF) and ET-1 was also conducted at different times. Concentrations of the extract (200, 400 and 700 µg/mL) were also added and incubated with the HT 29 cell lines for 24, 48 and 72 h time points. The effect of the tuber aqueous extract of the plant on nuclear factor-κB (NF-κB) expression after 2 h was also carried out using immunoblotting technique. Results The result showed that after 24 h, the effect of the extract in the presence of the mitogens and on the VSMC was more of proliferation. However, at 48 h, the 200 µg/mL dose, both alone and in the presence of VEGF caused 11.1% and 25.9% decreases respectively, in cell proliferation. In the HT 29 cytotoxic study the 200 µg/mL concentration caused the greatest cytotoxic effect at 77.1% cell inhibition followed by 400 µg/mL concentration at 71.4% after 72 h. The immunoblotting assay showed a down regulation of NF-κB expressions with 0.7 µg/mL concentration showing the greatest effect. NF-κB, a pro-inflammatory agent is increasingly recognized as a crucial player in many steps of cancer initiation and progression. Conclusions It could therefore be concluded that the aqueous root extract of Pueraria tuberosa possesses cytotoxic effect and could serve as a lead compound for anticancer and anti-inflammatory agents.