Naringin mitigates testicular injury and associated neuronal toxicity in lead-exposed cockerel chicks.

Objective: Lead (Pb) poisoning affects multiple organs including the reproductive system. The experiment was performed to explore the protective effect of naringin on testicular apoptosis, neuronal dysfunction and markers of stress in cockerel chicks. Materials and Methods: Thirty-six cockerel chicks were used for this study, and randomly grouped into six chicks per group viz. control, Pb only (600 ppm), Pb and naringin (80 mg/kg), Pb and Naringin (160 mg/kg), naringin only (80 mg/kg) and naringin only (160 mg/kg), respectively, for eight weeks. Pb was administered via drinking water while naringin was administered via oral gavage. Oxidative stress indices in the brain and testes were assessed, and immunohistochemistry of TNF-α and caspase 3 was done in the brain and testes, respectively. Results: Lead administration induced inflammatory and testicular apoptosis cascade accompanied with increased oxidative stress and upregulation of brain and testicular antioxidant enzymes in comparison to the control and Pb-only-treated cockerels. Immunohistochemistry showed significant immunoreactivity of testicular caspase 3 and TNF-α in the brain. Conclusion: Treatment of Pb-exposed chickens with naringin offered protection to Pb acetate-induced testicular oxidative stress, apoptosis, and neuroinflammation in cockerel chicks.

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 administration mitigates oxidative stress, anemia, and hypertension in lead acetate-induced cardio-renal dysfunction in cockerel chicks.

Lead is one of the major pollutants that is harmful to both animals and humans. It is found in every aspect of the environment such as the air, water, and soil. This pollutant affects both wild and domestic birds. Naringin has an active principle called flavonoid that has been found to have medicinal properties, mostly because of its antioxidant and metal chelating properties. This study was carried out to investigate the protective effect of naringin as an antioxidant against lead-induced anemia, cardio and nephrotoxicity, and hypertension. This study also aimed at elucidating the use of naringin as a heavy metal binder in poultry feed. Thirty-six cockerel chicks were used for this study, and randomly grouped into six groups per group; group A served as the control, group B received Pb-only (300 ppm), group C (Pb and naringin; 80 mg/kg), group D (Pb and naringin; 160 mg/kg), group E (naringin 80 mg/kg), and group F (naringin 160 mg/kg), respectively, for 8 weeks. Lead (Pb) was administered via drinking water, while naringin was administered via oral gavage. Lead acetate intoxication precipitated anemia as indicated by significant reductions in the values of PCV, RBC, and Hb concentration in lead-treated chicks when compared with the controls. Also, lead administration induced hypertension together with increased oxidative stress, depletion of the antioxidant defense system, reduced nitric oxide production, and an increase in high blood pressure. Immunohistochemistry indicated high expressions of cardiac troponin, renal angiotensin-converting enzymes, and renal neutrophil gelatinase-associated lipocalin. Treatment with naringin corrected anemia, reduced oxidative stress, improved antioxidant system, reduced high blood pressure, and offered protection against lead acetate-induced cardio-renal dysfunction in cockerel chicks. We recommend that naringin should be incorporated poultry feeds as a metal binder.

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.

Immunohistochemical and morphological changes associated with hepatic damage in lead acetate-induced toxicity and mitigatory properties of naringin in cockerel chicks.

Lead (Pb) toxicity constitutes a major health hazard to both humans and animals especially in the developing countries. It is a ubiquitous environmental contaminant found in the air essentially because of unregulated mining and other industrial activities. Lead can be found naturally in the soil thus, contaminating crops for human and animal food, as well as run-off water and air pollution. Intensively and extensively reared domestic chickens are exposed to contamination via inhalation and ingestion of contaminated food materials. Naringin, a product from citrus plant has been described to possess excellent metal chelating ability. Naringin is rich in flavonoid with attendant antioxidant, anti-autophagy, anti-inflammatory, hepatoprotective and cardio-nephroprotective properties. This study was conducted to investigate the hepatoprotective and modulation of oxidative stress in commercial cockerel chickens by Naringin. Thirty-six commercial cockerel chickens were randomly assigned into six groups A-F of six birds each viz: Group A served as control group while groups B, C, and D received Lead acetate at 300 ppm via drinking water continuously till the end of the experiment. In addition, groups C and D were treated with Naringin at 80 mg/kg and 160mg/kg, respectively, via oral gavage for 8 weeks. Groups E and F were administered naringin only at 80mg/kg and 160mg/kg respectively for eight weeks. Pb toxicity induced degenerative changes in the histological sections as well as, higher expression of hepatic caspase 3 as shown by immunohistochemistry. There was increased oxidative stress markers (H2O2, MDA) and depletion of the antioxidant defense system markers SOD, GPx, GSH, and GST. It concluded that Co- treatment with Naringin ameliorated oxidative stress, enhanced antioxidant defense system, reduced the expression of hepatic caspase 3 thus, offering protection against lead acetate-induced derangements in the liver of commercial cockerel chickens.

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.

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.

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.

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.

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.

Effects of caffeine and caffeic acid on selected biochemical parameters in L-NAME-induced hypertensive rats.

Biologically active compounds such as caffeine and caffeic acid can be obtained in plants especially cocoa and coffee. Hence, the combinatory effect of caffeine and caffeic acid as well as their individual effect were assessed on the activities of arginase, angiotensin-1-converting enzyme (ACE) as well as nitric oxide (NOx), and malondialdehyde (MDA) level in the Nω-Nitro-L-arginine-methylester (L-NAME)-induced hypertensive rats. The individual and combinatory effect of caffeine and caffeic acid were investigated in L-NAME-induced rats. Animals were grouped into eleven containing six animals each. Hemodynamic parameter was determined by tail-cuff plethysmography. Furthermore, the result showed a notable rise in ACE and arginase activities of L-NAME-induced group compared with the control group. However, pretreatment with test compounds lowered ACE, arginase activities, and MDA content with rise in NOx. This study supports that caffeine and caffeic acid combinations demonstrated antihypertensive properties by lowering the systolic blood pressure in L-NAME-induced rats. PRATICAL APPLICATIONS: This duo bioactive compounds; caffeine (alkaloid) and caffeic acid (phenolic acid) are lavishly distributed in coffee. Their cardiopotective and cardiomodulatory roles have been investigated due to their biological activities. As far as we are aware, this could be foremost in-depth study on the antihypertensive and cardioprotective effect of the combinations of caffeine and caffeic acid targeting the key enzymes system relevant to hypertension. Decreased ACE and arginase activities as well as high nitric oxide (NOx) and low MDA level may be associated with its antihypertensive effect. This present study suggests that the combinations of this phenolics and alkaloid compound might proffer a therapeutic strategy in the management of hypertension.

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.

Ramipril blunts glycerol-induced acute renal failure in rats through its antiapoptosis, anti-inflammatory, antioxidant, and renin-inhibiting properties.

OBJECTIVES: Acute kidney injury (AKI) is a malady with a sudden onset resulting in buildup of waste matters in the body, but a specific cure hasn't been found as a lasting solution to AKI. In this study, ramipril was evaluated for its potential therapy in glycerol-induced AKI in rats. METHODS: Twenty animals were divided into four groups of five animals each. Group I was the control while group II was given glycerol on day 8 only, groups III and IV were administered with pioglitazone (reference drug) and ramipril for seven days respectively and on day 8 received glycerol. On the ninth day, blood and tissue samples were taken to assay for serum indicators of oxidative damage, enzymatic and nonenzymatic antioxidants, and creatinine and blood urea nitrogen. Animals were sacrificed thereafter; kidney was harvested for histological and immunohistochemical analysis. Expressions of caspase 3, renin receptor, NK-KB, and KIM-1 were carried out. RESULTS: Ramipril significantly inhibited indicators of oxidative damage while also significantly increasing levels of enzymatic and nonenzymatic antioxidant markers. These drugs also significantly lowered the levels of creatinine and blood urea nitrogen. Histology also indicated that while there were massive infiltration of leucocytes and congestion of the kidney in toxicant group, the ramipril-treated group showed a milder condition. In immunohistochemistry, the two drugs significantly inhibited the expressions of the four proteins, which were highly expressed in the toxicant group. CONCLUSIONS: The study showed that ramipril and pioglitazone have nephroprotective effect and thus have the ability to blunt AKI through their anti-inflammatory, antiapoptosis, antirenin, and antioxidant properties.

Methanol leaf extract of Momordica charantia protects alloxan-induced hepatopathy through modulation of caspase-9 and interleukin-1ß signaling pathways in rats.

BACKGROUND AND AIM: Momordica charantia is a highly valued plant, widely distributed in the tropical and subtropical regions. The plant is reported to have a wide range of medicinal uses. This study was designed to explore the ameliorative potential of M. charantia methanol leaf extract in alloxan-induced diabetic animal model with a particular focus on the liver. MATERIALS AND METHODS: Hepatoprotective effect of methanol leaf extract of M. charantia was assessed in alloxan-induced toxicity in 50 rats divided into five groups (A-E) (n=10). Group A normal control, Group B was toxicant group, and Group C animals received glibenclamide treatment while Groups D and E received extracts at 200 and 400 mg/kg doses, respectively. The experiment lasted for 28 days. Histopathological changes, blood glucose level, and serum enzymes such as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, oxidative status and caspase-9, and interleukin-1ß (IL-1ß) were evaluated. RESULTS: Extract-treatment caused a decreased blood glucose level, markers of oxidative stress such as malondialdehyde and hydrogen peroxide (H2O2). Treatment of rats with leaf extract of M. charantia resulted in increased levels and activities of protein thiols, non-protein thiols, glutathione (GSH), glutathione peroxidase, glutathione S-transferase, and superoxide dismutase indicating its antioxidant potential. The liver section revealed mild distortion of the hepatic architecture compared to the toxicant group, while decreased expressions of caspase-9 and IL-1ß in extract-treated groups was observed. CONCLUSION: The plant extract exhibited antioxidant, anti-apoptotic, and anti-inflammatory effects, thus showing its hepatoprotective property.

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.