Cardiovascular and renal oxidative stress-mediated toxicities associated with bisphenol-A exposures are mitigated by Curcuma longa in rats.

Objective: Curcuma longa Rhizome (CLR), due to its potent antioxidant phytochemical constituents, was investigated for its effects on bisphenol A (BPA)-induced cardiovascular and renal damage. Materials and Methods: Sixty rats were randomly selected, and grouped as control, BPA (100 mg/ kg), BPA and CLR 100 mg/kg, BPA and CLR 200 mg/kg, CLR 100 mg/kg, and CLR 200 mg/kg for 21 days. Oxidative stress indices, antioxidant status, blood pressure parameters, genotoxicity, and immunohistochemistry were determined. Results: Rats exposed to the toxic effects of BPA had heightened blood pressure, lowered frequency of micronucleated polychromatic erythrocytes, and decreased activities of antioxidant enzymes compared with rats treated with CLR. Moreover, administration of CLR significantly (p<0.05) lowered malondialdehyde content and reduced the serum myeloperoxidase activity. Immunohistochemical evaluation revealed significantly (p<0.05) increased expressions of cardiac troponin and Caspase 3 in the BPA group compared with the CLR-treated groups. Conclusion: C. longa ameliorated cardiotoxic and nephrotoxic actions of bisphenol-A via mitigation of oxidative stress, hypertension, and genotoxicity.

Leaf extract of Anacardium occidentale ameliorates biomarkers of neuroinflammation, memory loss, and neurobehavioral deficit in N(ω)-nitro-L-arginine methyl ester (L-NAME) treated rats.

PURPOSE: Anacardium occidentale commonly known as Cashew is a plant that is widely used in African traditional medicine. It is endowed with phytochemical constituents that are responsible for its medicinal properties. METHODS: Twenty-five male Wistar rats were grouped as follows: Control (Group A), Group B (L-NAME 40 mg/kg), Group C (100 mg/kg Anacardium occidentale extract plus 40 mg/kg L-NAME), Group D (200 mg/kg extract plus 40 mg/kg L-NAME) and Group E (10 mg/kg of Lisinopril plus 40 mg/kg L-NAME). The animals were treated with oral administration of either the extracts or Lisnopril daily for 4 weeks. Neuro-behavioural tests such as the Morris Water Maze and Hanging Wire Grip tests were carried out to evaluate memory/spatial learning and muscular strength, respectively. Makers of oxidative stress, antioxidant enzymes and immunohistochemical staining of Glial Fibrillary Acidic Protein and Ionised Calcium Binding Adaptor molecule 1 were assessed. RESULTS: L-NAME administration caused significant increases in biomarkers of oxidative stress, decreased antioxidant status, acetylcholinesterase activity, altered neuro-behavioural changes, astrocytosis, and microgliosis. However, Anacardium occidentale reversed exaggerated oxidative stress biomarkers and improved neuro-behavioural changes. CONCLUSIONS: Combining all, Anacardium occidentale enhanced brain antioxidant defence status, improved memory and muscular strength, thus, suggesting the neuroprotective properties of Anacardium occidentale.

Naringin abrogates angiotensin-converting enzyme (ACE) activity and podocin signalling pathway in cobalt chloride-induced nephrotoxicity and hypertension.

PurposeThe persistent and alarming rates of increase in cardiovascular and renal diseases caused by chemicals such as cobalt chloride (CoCl2) in mammalian tissues have led to the use of various drugs for the treatment of these diseases. This study aims at evaluating the nephron-protective action of Naringin (NAR), a metal-chelating antioxidant against CoCl2-induced hypertension and nephrotoxicity.MethodsForty-two male Wistar rats were randomly distributed to seven rats of six groups and classified into Group A (Control), Group B (300 part per million; ppm CoCl2), Group C (300 ppm CoCl2 + 80 mg/kg NAR), Group D (300 ppm CoCl2 + 160 mg/kg NAR), Group E (80 mg/kg NAR), and Group F (160 mg/kg NAR). NAR and CoCl2 were administered via oral gavage for seven days. Biomarkers of renal damage, oxidative stress, antioxidant status, blood pressure parameters, immunohistochemistry of renal angiotensin-converting enzyme and podocin were determined.ResultsCobalt chloride intoxication precipitated hypertension, renal damage, and oxidative stress. Immunohistochemistry revealed higher expression of angiotensin-converting enzyme (ACE) and podocin in rats administered only CoCl2.ConclusionTaken together, the antioxidant and metal-chelating action of Naringin administration against cobalt chloride-induced renal damage and hypertension could be through abrogation of angiotensin-converting enzyme and podocin signalling pathway.

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.

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.

Luteolin normalizes blood pressure via its antioxidant activity and down-regulation of renal Angiotensin II receptor and Mineralocorticoid receptor expressions in rats co-exposed to Diclofenac and sodium fluoride.

This study was designed to investigate the modulatory role of Luteolin (Lut), a flavonoid phytochemical, on haemodynamic parameters and the potential mechanisms involving renal Angiotensin II (AT2R) and Mineralocorticoid (MCR) receptors in renal toxicity induced by co-exposure to Diclofenac (Dcf) and sodium fluoride (NaF) in rats.Male Wistar rats were administered with either vehicle (control), Dcf only (9 mg/kg orally) or concurrently with NaF (300 ppm in drinking water). Other groups were treated with LutA (100 mg/kg) or LutB (200 mg/kg) along with Dcf and NaF exposures. All treatments lasted 8 days, following which blood pressure indices were measured using tail-cuff plethysmography. Renal expressions of AT2R and MCR were studied with immunohistochemistry, while biomarkers of oxidative and antioxidant status were also measured in the kidneys. Systolic, diastolic and mean arterial pressures were significantly (p<0.05) reduced in Dcf-treated rats, compared to control values. However, co-treatment with NaF or Lut restored these parameters. While the expression of AT2R and MCR was high in the Dcf and Dcf+NaF groups, treatment with Lut caused obvious reduction in the renal expression of these receptors. Increased lipid peroxidation (Malondialdehyde) and protein oxidation (protein carbonyls) with a lowering of reduced glutathione levels contributed to the renal toxicity of Dcf, and these were significantly ameliorated in Lut-treated rats. In conclusion, the preservation of haemodynamic indices by Lutin the experimental ratsprobably included mechanisms involving down-regulation of renal expressions of AT2R and MCR, reduction of oxidative stress and an improvement of renal antioxidant status.

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.

Clofibrate, a Peroxisome Proliferator-Activated Receptor-Alpha (PPARα) Agonist, and Its Molecular Mechanisms of Action against Sodium Fluoride-Induced Toxicity.

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.

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.

Luteolin mitigates potassium dichromate-induced nephrotoxicity, cardiotoxicity and genotoxicity through modulation of Kim-1/Nrf2 signaling pathways.

Environmental and occupational exposure to chromium compounds has become potential aetiologic agent for kidney disease with excessive generation of free radicals, apoptosis, and inflammatory. These pathophysiologic mechanisms of potassium dichromate (K2 Cr2 O7 ) have been well correlated with nephrotoxicity and cardiotoxicity. The cardioprotective and nephroprotective effects of Luteolin, a known potent antioxidant were evaluated in this study with 40 healthy rats in four experimental groups: Group A (normal saline), Groups B (30 mg/kg K2 Cr2 O7 ), Group C (Luteolin 100 mg/kg and K2 Cr2 O7 30 mg/kg), and Group D (Luteolin 200 mg/kg and K2 Cr2 O7 30 mg/kg), respectively. Markers of antioxidant defense system, oxidative stress, blood pressure and micronucleated polychromatic erythrocytes (MnPEs), immunohistochemistry of Kidney, injury molecule (Kim-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and cardiac troponin I were determined. Administration of K2 Cr2 O7 increased blood pressure parameters in systolic, diastolic and mean arterial blood pressures, markers of oxidative stress, and frequency of micronucleated polychromatic erythrocytes, together with reduction in serum nitric oxide level. Renal Kim-1 and cardiac troponin I expressions were higher, but lower expressions of renal and cardiac Nrf2 were recorded with immunohistochemical analysis. Pre-treatment with Luteolin restored blood pressure parameters, with concomitant reduction in oxidative stress indicators, augmented antioxidant mechanisms and serum Nitric oxide level, lowered the expressions of Kim-1, cardiac troponin I and up-regulated of both cardiac and renal Nrf2, reduced the frequency of micronucleated polychromatic erythrocytes. Taken together, this study therefore demonstrates the cardioprotective, nephro protective and antigenotoxic effects of Luteolin through antioxidantive and radical scavenging mechanisms.

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.

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.

Luteolin Attenuates Glycerol-Induced Acute Renal Failure and Cardiac Complications Through Modulation of Kim-1/NF-κB/Nrf2 Signaling Pathways.

Acute renal failure (ARF) has been documented as a life-threatening disease with high morbidity and mortality. We investigated the protective effect of Luteolin against ARF. In this study, forty-male Wistar albino rats were randomly divided into four groups (n = 10). Group A received normal saline. Group B received glycerol (10 ml/kg BW, 50% v/v in sterile saline, i.m.). Groups C and D were pretreated with Luteolin 100 and 200 mg/kg for 7 days, and thereafter administered Glycerol (10 ml/kg BW, 50% v/v in sterile saline, i.m.). Administration of glycerol significantly increased systolic blood pressure, diastolic blood pressure and mean arterial pressure. Renal protein carbonyl and xanthine oxidase increased significantly while significant reduction in the activity of renal glutathione peroxidase, glutathione S-transferase and glutathione reductase was observed in the glycerol intoxicated rats. Furthermore, administration of glycerol led to significant increases in serum creatinine and blood urea nitrogen together with reduction in nitric oxide (NO) bioavailability. Immunohistochemistry revealed that glycerol intoxication enhanced expressions of kidney injury molecule 1, nuclear factor kappa beta and cardiac troponin (CTnI). However, Luteolin pretreatment normalized blood pressure, reduced markers of oxidative stress, renal damage, and improved NO bioavailability. Luteolin also downregulated the expressions of kidney injury molecule 1, nuclear factor kappa beta and cardiac troponin. Together, Luteolin might open a novel therapeutic window for the treatment of acute renal failure and cardiac complication.

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.

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

Hypertension is a condition with chronic elevation of blood pressure and a common preventable risk factor for cardiovascular disease with attendant global morbidity and mortality. The present study investigated the novel antihypertensive and neuroprotective effect of Naringenin on L-NG-Nitro arginine methyl ester (L-NAME) induced hypertension together with possible molecular mechanism of action. Rats were divided into four groups. Rats in Group A were normotensive. The hypertensive group (Group B) received 40 mg/kg) of L-NAME alone while Groups C and D were concurrently administered Naringenin (50 mg/kg) or Lisinopril (10 mg/Kg) together with L-NAME orally for 3 weeks. Blood pressure parameters, markers of oxidative stress and renal damage were measured. The immunohistochemistry of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme were also determined. Results indicated significant increases in malondialdehyde, advanced oxidation protein products, protein carbonyl contents and decrease in serum nitric oxide bioavailability in hypertensive rats. Furthermore, there were significant increases in serum myeloperoxidase, urinary creatinine, albumin and blood urea nitrogen in hypertensive rats in comparison to hypertensive rats treated with either Naringenin or Lisinopril. Immunohistochemistry reveal significant expressions of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme in hypertensive rats. However, co-treatment with either Naringenin or Lisinopril mitigated both renal and neuronal oxidative stress, normalized blood pressure and lowered the expressions of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme. Collectively, Naringenin offered a novel antihypertensive and neuroprotective effect through down regulation of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme.

Clofibrate, a PPAR-α agonist, abrogates sodium fluoride-induced neuroinflammation, oxidative stress, and motor incoordination via modulation of GFAP/Iba-1/anti-calbindin signaling pathways.

Fluoride is an environmental contaminant that is ubiquitously present in air, water, and soil. It is commonly added in minute quantity to drinking water, toothpaste, and mouth rinses to prevent tooth decay. Epidemiological findings have demonstrated that exposure to fluoride induced neurodevelopmental toxicity, developmental neurotoxicity, and motor disorders. The neuroprotective effect of clofibrate, a peroxisome proliferator-activated receptor alpha agonist, was investigated in the present study. Forty male Wistar rats were used for this study and randomly grouped into 10 rats per group as control, sodium fluoride (NaF) alone (300 ppm), NaF plus clofibrate (250 mg/kg), and NaF plus lisinopril (10 mg/kg), respectively, for 7 days. NaF was administered in drinking water while clofibrate and lisinopril were administered by oral gavage. Markers of neuronal inflammation and oxidative stress, acetylcholinesterase activity, and neurobehavioral (hanging wire and open field) tests were performed. Immunohistochemistry was performed on brain tissues, and they were probed with glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, and cerebellar Ca2+ -binding protein calbindin-D28k. The results showed that NaF significantly increased of oxidative stress and neuroinflammation and inhibited AChE activity. Immunostaining showed reactive astrocytes, microgliosis, loss of dendritic spines, and arborization in Purkinje cells in rats administered only NaF. Neurobehavioral results showed that cotreatment of NaF with clofibrate improved muscular strength and locomotion, reduced anxiety, and significantly reduced astrocytic count. Overall, cotreatment of NaF with either clofibrate or lisinopril showed neuroprotective effects by mitigating neuronal inflammation and oxidative and motor incoordination. Hence, clofibrate could be seen as a novel drug candidate against neurodegeneration and motor disorders.

Effect of the methanol extract of the red cultivar Allium cepa L. on the serum biochemistry and electrolytes of rats following sub-chronic oral administration.

Background In traditional medicine, Allium cepa Linnaeus is used for the treatment of several disease conditions. Whilst reports abound on the effects of several cultivars of A. cepa L on biochemical parameters, similar information on the red cultivar is scarce. This study examines the effects of the methanol extract of the red cultivar A. cepa L on some serum biochemical parameters in experimental Wistar rats. Materials and methods Fifty-five Wistar rats were divided into three groups (A, B and C), which include 25, 25 and 5 rats, respectively. The rats in Groups A and B were sub-divided into 5 groups of 5 rats. Each rat was administered a certain dose of methanol extract of the red cultivar A. cepa L for 14 days (Group A) or 28 days (Group B). Group C rats served as the control and were administered with distilled water (10 mL/kg). Results A. cepa L administration resulted in dyslipidaemia, hyponatremia, hypokalaemia and hyperchloraemia; a significant (p < 0.05) decrease in hepatic enzymes and a significant (p < 0.05) increase in serum bicarbonate, bilirubin and its fractions. Conclusions These biochemical results indicate that the excessive and prolonged medicinal consumption of A. cepa L products beyond 7 days may induce moderate hepatic injury and mild renal dysfunction and may complicate disease conditions, such as hypertension and diabetes. Thus, in order to minimize its toxic effects, it is recommended that A. cepa L products should not be used for more than seven consecutive days or beyond a dosage of 90 mg/kg.