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.

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.

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.

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.

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

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

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

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

Quercetin attenuates hypertension induced by sodium fluoride via reduction in oxidative stress and modulation of HSP 70/ERK/PPARγ signaling pathways.

Hypertension is one of the silent killers in the world with high mortality and morbidity. The exposure of humans and animals to fluoride and/or fluoride containing compounds is almost inevitable. This study investigated the modulatory effects of quercetin on sodium fluoride (NaF)-induced hypertension and cardiovascular complications. Forty male rats were randomly separated into four groups (n =10). Group A animals served as the control, rats in Group B were exposed to 300 ppm of NaF, Groups C and D animals were exposed to 300 ppm of NaF along with quercetin orally at 50 mg/kg and 100 mg/kg orally by gavage, while NaF was administered in drinking water, respectively, for a week. Administration of NaF caused severe hypertension as indicated with significant increases in the systolic, diastolic, and mean arterial blood pressure, together with prolonged ventricular depolarization (QRS) and the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT) intervals when compared with controls. NaF significantly decreased the activities of antioxidant enzymes, caused increase in markers of oxidative stress and renal damage when compared with controls. Immunohistochemical staining revealed lower expressions of Hsp70, ERK, and PPARγ in the heart, kidney, and aorta of rats-administered NaF relative to the controls. Together, quercetin co-treatment with NaF restored blood pressure, normalized QRS interval, and improved antioxidant defense system. © 2018 BioFactors, 44(5):465-479, 2018.

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.

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.

Sodium arsenite-induced cardiovascular and renal dysfunction in rat via oxidative stress and protein kinase B (Akt/PKB) signaling pathway.

OBJECTIVES: Arsenic is a ubiquitous element that is widely distributed in the environment to which man and animals are exposed. Cardiovascular disease is one of the aftermaths of chronic arsenic exposure-related morbidity and mortality. This study sought to investigate the possibility of reversal from arsenic-induced cardio-renal toxicity following exposure and subsequent withdrawal. The study also seeks to understand the mechanism of action of this reversal. METHODS: Rats were orally exposed to sodium arsenite at 10, 20 and 40 mg/kg daily for 4 weeks followed by 4 weeks of withdrawal. RESULTS: Exposure to arsenic caused a significant increase in malondialdehyde, H2O2 generation but decrease total thiol and reduced glutathione levels in both cardiac and renal tissues. Furthermore, increases in superoxide dismutase, glutathione-S-transferase and catalase with significant increases in glutathione peroxidase activities were observed in the cardiac tissues. On the contrary, a significant reduction in the renal antioxidant enzyme activity was recorded following exposure. Also, antioxidant defense system did not return to apparent values after arsenic withdrawal. Immunohistochemistry revealed a reduction in the expression of the pro-survival protein-protein kinase B (Akt/PKB) following exposure to arsenic and this was not reversed by withdrawal Discussion: Exposure to arsenic caused cardio-renal toxicity via induction of oxidative stress and down-regulation of Akt/PKB expressions.

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

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

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

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

Cobalt chloride exposure dose-dependently induced hepatotoxicity through enhancement of cyclooxygenase-2 (COX-2)/B-cell associated protein X (BAX) signaling and genotoxicity in Wistar rats.

Cobalt chloride (CoCl2 ) is one of the many environmental contaminants, used in numerous industrial sectors. It is a pollutant with deadly toxicological consequences both in developing and developed countries. We investigated toxicological impact of CoCl2 on hepatic antioxidant status, apoptosis, and genotoxicity. Forty Wistar rats were divided into four groups, 10 rats per group: Group 1 served as control and received clean tap water orally; Group 2 received CoCl2 solution (150 mg/L); Group 3 received CoCl2 solution (300 mg/L); and Group 4 received CoCl2 (600 mg/L) in drinking water for 7 days, respectively. Exposure of rats to CoCl2 led to a significant decline in hepatic antioxidant enzymes together with significant increase in markers of oxidative stress. Immunohistochemistry revealed dose-dependent increase in cyclooxygenase-2 and BAX expressions together with increased frequency of Micronucleated Polychromatic Erythrocytes. Combining all, CoCl2 administration led to hepatic damage through induction of oxidative stress, inflammation, and apoptosis.

Modulatory effects of melatonin and vitamin  C on oxidative stress-mediated haemolytic anaemia and associated cardiovascular dysfunctions in rats.

Background Phenylhydrazine (PHE) in experimental animal models has been widely reported to cause haemolytic anaemia, via the induction of oxidative stress and thus causing deleterious cardiovascular complications. Hence, this study was designed to evaluate the possible modulatory role of melatonin (MLT) or vitamin C when co-administered with PHE. Methods Anaemia was established with PHE administration. MLT or vitamin C was co-administered with PHE. Haematological parameters, markers of oxidative stress, enzymic and non-enzymic antioxidants, blood pressure and electrocardiograms were assessed. Results PHE administration led to a significant (p<0.05) increase in malondialdehyde (MDA), and hydrogen peroxide (H2O2) generated in cardiac, renal and red blood cell (RBC) lysates. PHE also significantly reduced the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD) and reduced glutathione (GSH) contents, respectively. The RBC counts, haemoglobin (Hb) concentration and packed cell volume (PCV) were also significantly reduced following the administration of PHE. Furthermore, the systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MABP) increased significantly in rats administered PHE alone. Similarly, PHE administration led to a significant drop in heart rate but prolonged QRS, QT and QTc interval. Pathology of the heart and kidney was also observed in PHE treated group. However, treatment with MLT and vitamin C improved enzymic and non-enzymic antioxidant system together with the restoration of SBP, DBP and MABP to near normal. The architectural anarchy observed in the heart and kidney of PHE administered rats was reversed to some extent. Conclusions Hence, MLT and vitamin C could be employed as therapeutic targets in various cardiovascular diseases and its complications.

Sodium fluoride induces hypertension and cardiac complications through generation of reactive oxygen species and activation of nuclear factor kappa beta.

Human exposure to sodium fluoride through its daily usage is almost inevitable. Cardiovascular and renal dysfunction has been associated with fluoride toxicity. Therefore, this study investigated the mechanism of action of sodium fluoride (NaF) induced hypertension and cardiovascular complications Forty male albino rats of an average of 10 rats per group were used. Group A received clean tap water. Toxicity was induced in Group B to D by administering graded doses of NaF through drinking water ad libitum for 10 days at 150 ppm, 300 ppm, and 600 ppm concentration respectively. Following administration of NaF, there was significant increase in systolic pressure, diastolic pressure and mean arterial pressure. Markers of oxidative stress; malondialdehyde, hydrogen peroxide, advance oxidation protein products, and protein carbonyl were significantly increased in dose-dependent pattern in the cardiac and renal tissues of rats together with significant decrease in the GST activity in NaF-treated rats compared to the control. Also serum markers of inflammation, cardiac, and renal damage including myeloperoxidase, xanthine oxidase, blood urea nitrogen, creatinine, Lactate dehydrogenase (LDH), and Creatinine kinase myocardial band (CK-MB) significantly increased indicating induction of oxidative stress, renal, and cardiac damage after exposure. Histopathology of the kidney and heart revealed aberrations in the histological architecture in NaF-treated rats. Also, immunohistochemistry showed higher expression of nuclear factor kappa beta (NF-kB) in the cardiac and renal tissues of rats administered NaF. Combining all, these results indicate NaF-induced hypertension through generation of reactive oxygen species and activation of renal and cardiac NF-kB expressions. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1089-1101, 2017.

Quercetin and Vitamin C Mitigate Cobalt Chloride-Induced Hypertension through Reduction in Oxidative Stress and Nuclear Factor Kappa Beta (NF-Kb) Expression in Experimental Rat Model.

The objective of the present work was to evaluate the toxic effects of cobalt chloride, a potent oxidative stress-inducing chemical, at 650 ppm in rats and the protective effect of quercetin and/or vitamin C against the cobalt chloride-induced toxicity. Thirty rats were randomly selected, and assigned to one of five groups: control, cobalt chloride, cobalt chloride + quercetin, cobalt chloride + vitamin C and cobalt chloride + quercetin + vitamin C. The exposure of rats to cobalt chloride led to a significant increase (p < 0.05) in malondialdehyde (MDA) and hydrogen peroxide (H2O2) generated, but decreased nitric oxide (NO) bioavailability. Also, significant (p < 0.05) reductions were observed in the activity of glutathione peroxidase (GPx) and reduced glutathione (GSH) content in the cardiac and renal tissues. Treatment with quercetin and vitamin C reversed the effect of cobalt chloride on MDA, H2O2 and NO, more potently than with either of the two antioxidants, and increased the antioxidant defence system. Further, treatment of rats with quercetin and vitamin C in combination resulted in significant (p < 0.05) decreases in the systolic, diastolic, and mean arterial blood pressure of rats, relative to those exposed to cobalt chloride alone. Immunohistochemical studies revealed a greater expression of nuclear factor kappa beta (NF-kB) in the cobalt chloride group compared with the control- and antioxidants-treated rats. The results of this study suggest a protective role for quercetin and vitamin C in the amelioration of the toxic mechanisms leading to cobalt chloride-induced hypertension and its associated cardiac and renal complications in rats.

Mitigation of diazinon-induced cardiovascular and renal dysfunction by gallic acid.

Studies of the link between environmental pollutants and cardiovascular dysfunction, neglected for decades, have recently provided new insights into the pathology and consequences of these killers. In this study, rats were divided into four groups, each containing 10 rats. The rats in group one served as controls and were administered normal saline, whereas the rats in group two were orally gavaged with 3 mg/kg of diazinon (DZN) alone for twenty one consecutive days. The rats in groups 3 and 4 were administered respective 60 mg/kg and 120 mg/kg gallic acid (GA) in addition to DZN for twenty one consecutive days. Exposure of rats to diazinon significantly (p<0.05) reduced the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) content. Malondialdehyde, hydrogen peroxide (H2O2) and nitric oxide (NO) contents were also significantly (p<0.05) elevated following DZN exposure. DZN further caused a significant (p<0.05) decrease of heart rate and QT interval prolongation. Hematologic analysis revealed significant reduction (p<0.05) in packed cell volume (PCV), hemoglobin concentration (Hb), red blood cell (RBC) count, and total white blood cell count of rats administered only DZN. Observations in this study suggest a modulatory role of gallic acid in diazinon-induced anemia and associated cardiovascular dysfunction in rats. Treatment with gallic acid reversed the oxidative stress markers studied, increased the antioxidant defence system and reduced deleterious effects on hematological parameters in rats. Pathologic findings of the heart and kidney were also found to be lessened.